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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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Objective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases. Design: Experimental study. Subjects: Brown Norway rats and New Zealand White Cross rabbits. Methods: Preclinical study data of RO-101 in terms of target-specific enzyme-linked immunosorbent assay binding affinity to VEGF-A and Ang-2, vitreous half-life, inhibition of target-receptor interaction, laser choroidal neovascular membrane animal model, human umbilical vein endothelial cell migration, and biocompatibility was obtained. Where applicable, study data were compared with other anti-VEGF agents. Main Outcome Measures: Binding affinity, half-life, biocompatibility, and efficacy of RO-101. Neovascularization prevention by RO-101. Results: RO-101 demonstrated a strong binding affinity for VEGF-A and Ang-2 and in vitro was able to inhibit binding to the receptor with higher affinity than faricimab. The half-life of RO-101 is comparable to or longer than current VEGF inhibitors used in retinal disease. RO-101 was found to be biocompatible with retinal tissue in Brown Norway rats. RO-101 was as effective or more effective than current anti-VEGF therapeutics in causing regression of neovascular growth in vivo. Conclusions: RO-101 is a promising candidate for use in retinal diseases. In preclinical models, RO-101 demonstrated similar or higher regression of neovascular growth to current anti-VEGF therapeutics with comparable or longer half-life. It also demonstrates a strong binding affinity for VEGF-A and Ang-2. It also was shown to be biocompatible with retinal tissue in animal studies, indicating potential compatibility for use in humans. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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PURPOSE: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience. METHODS: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection. RESULTS: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal and choroidal therapeutics. The panel established consensus on the rationale for SCS injection, including potential benefits relative to other intraocular delivery methods and current best practices in patient preparation, pre- and peri-injection management, SCS-specific injection techniques, and postinjection management and follow-up. CONCLUSION: These expert panel guidelines may support and promote standardization of SCS injection technique, with the goal of optimizing patient safety and outcomes. Some aspects of the procedure may reasonably be modified based on the clinical setting and physician judgment, as well as additional study.
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Corioide , Humanos , Injeções Intraoculares , Doenças Retinianas , Guias de Prática Clínica como AssuntoRESUMO
Indicated for colorectal cancer for decades, bevacizumab has been widely used off label to treat retinal diseases, and the benefits of its use, specifically in neovascular age-related macular degeneration, have been demonstrated in multiple clinical trials. The intravitreal delivery of bevacizumab requires it to be aseptically repackaged into individual syringes by compounding pharmacies for use in the eye. Although the repackaging process is permitted by the US Food and Drug Administration, the resultant product does not meet the specific standards of products approved for use as ophthalmic injectables nor is the parenteral innovator solution compliant with ophthalmic standards. Studies have also demonstrated variability in the quality and quantity of repackaged bevacizumab. This narrative review summarizes the evidence and discusses the role of off-label bevacizumab in the treatment and management of retinal diseases, its mechanism of action, current challenges and provides a critical appraisal of current evidence, clinical implications, and future directions. [Ophthalmic Surg Lasers Imaging Retina 2024;55:155-162.].
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Degeneração Macular , Doenças Retinianas , Humanos , Bevacizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Injeções , Degeneração Macular/tratamento farmacológico , Doenças Retinianas/tratamento farmacológico , Injeções IntravítreasRESUMO
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 , Retinopatia Diabética , Edema Macular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/complicações , Inibidores da Angiogênese/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Injeções Intravítreas , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento , Diabetes Mellitus/tratamento farmacológicoRESUMO
BACKGROUND/OBJECTIVE: Investigate real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). SUBJECTS/METHODS: Multicenter, retrospective chart review was conducted on patients treated with faricimab for nAMD from February 2022 to September 2022. Collected data includes background demographics, treatment history, best-corrected visual acuity (BCVA), anatomic changes, and adverse events as safety markers. The main outcome measures are changes in BCVA, changes in central subfield thickness (CST) and adverse events. Secondary outcome measures included treatment intervals and presence of retinal fluid. RESULTS: After one injection of faricimab, all eyes (n = 376), previously-treated (n = 337) and treatment-naïve (n = 39) eyes demonstrated a + 1.1 letter (p = 0.035), a + 0.7 letter (p = 0.196) and a + 4.9 letter (p = 0.076) improvement in BCVA, respectively, and a - 31.3 µM (p < 0.001), a - 25.3 µM (p < 0.001) and a - 84.5 µM (p < 0.001) reduction in CST, respectively. After three injections of faricimab, all eyes (n = 94), previously-treated (n = 81) and treatment-naïve (n = 13) eyes demonstrated a + 3.4 letter (p = 0.03), a + 2.7 letter (p = 0.045) and a + 8.1 letter (p = 0.437) improvement in BCVA, and a - 43.4 µM (p < 0.001), a - 38.1 µM (p < 0.001) and a - 80.1 µM (p < 0.204) reduction in CST, respectively. One case of intraocular inflammation was observed after four injections of faricimab and resolved with topical steroids. One case of infectious endophthalmitis was treated with intravitreal antibiotics and resolved. CONCLUSIONS: Faricimab has demonstrated improvement or maintenance of visual acuity for patients with nAMD, along with rapid improvement of anatomical parameters. It has been well-tolerated with low incidence of treatable intraocular inflammation. Future data will continue to investigate faricimab for real-world patients with nAMD.
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Inibidores da Angiogênese , Degeneração Macular , Humanos , Inibidores da Angiogênese/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , InflamaçãoRESUMO
PURPOSE: Retinal vasculitis or vascular occlusion (RV/RO) have been reported after brolucizumab for neovascular age-related macular degeneration. This systematic literature review evaluated RV/RO events after brolucizumab in real-world practice. METHODS: Systematic literature searches identified 89 publications; 19 were included. RESULTS: Publications described 63 patients (70 eyes) with an RV/RO event following brolucizumab. Mean age was 77.6 years and 77.8% of patients were women; 32 eyes (45.7%) received one brolucizumab injection before RV/RO. Mean (range) time to event from last brolucizumab injection was 19.4 (0-63) days, with 87.5% of events occurring within 30 days. Among eyes with preevent and postevent visual acuity (VA) assessments, 22/42 eyes (52.4%) showed unchanged (±0.08 logMAR) or improved vision from last recorded preevent assessment at latest follow-up, whereas 15/42 eyes (35.7%) showed ≥0.30 logMAR (≥15 letters) VA reduction. Patients with no VA loss were on average slightly younger and had a higher proportion of nonocclusive events. CONCLUSION: Most RV/RO events reported after brolucizumab in early real-world practice occurred in women. Among eyes with VA measurements, approximately half experienced VA loss; overall, about one-third had VA reduction of ≥0.30 logMAR at latest follow-up, with indications of regional variations.
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Anticorpos Monoclonais Humanizados , Degeneração Macular , Vasculite Retiniana , Humanos , Masculino , Feminino , Idoso de 80 Anos ou mais , Vasculite Retiniana/induzido quimicamente , Degeneração Macular/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , IdosoRESUMO
PURPOSE: To assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU). METHODS: Patients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control). RESULTS: Over the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed. CONCLUSION: Approximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.
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Edema Macular , Triancinolona Acetonida , Glucocorticoides/efeitos adversos , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Magnolia , Tomografia de Coerência Óptica , Resultado do Tratamento , Triancinolona Acetonida/efeitos adversos , Uveíte/complicações , Uveíte/tratamento farmacológicoRESUMO
PURPOSE: To evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU). DESIGN: Open-label, prospective multicentre safety study. PARTICIPANTS: Thirty-eight subjects with NIU, with and without macular oedema (MO). METHODS: Treatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations. MAIN OUTCOME MEASURES: The main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST). RESULTS: Based on a CST of >300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; one of which was deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was <1 ng/mL. Efficacy parameters showed improvement over the 24-week study period. CONCLUSIONS: Suprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO.
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Infecções Oculares Bacterianas , Edema Macular , Uveíte , Infecções Oculares Bacterianas/tratamento farmacológico , Glucocorticoides , Humanos , Edema Macular/tratamento farmacológico , Estudos Prospectivos , Retina , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Triancinolona Acetonida , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Acuidade VisualRESUMO
PURPOSE: To assess the relationship between best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) features in noninfectious uveitis (NIU)-related macular edema. DESIGN: Clinical cohort study from post hoc analysis of 2 phase 3 clinical trials. METHODS: Correlation and longitudinal treatment analyses were performed. Of 198 patients with NIU, 134 received suprachoroidal CLS-TA (proprietary formulation of a triamcinolone acetonide injectable suspension), and 64 received sham, with 12.9% and 72%, respectively, receiving rescue therapy. RESULTS: At baseline, mean BCVA progressively worsened with each ordinal drop in central subfield ellipsoid zone (EZ) integrity. Eyes with normal baseline EZ experienced greater 24-week change in BCVA versus those with some degree of baseline EZ disruption (11.9 vs 9.4 letters, P = .006). In contrast, eyes with baseline central subfield cystoid spaces and/or subretinal fluid showed more improvement (13.7 or 17.2 letters, respectively) at 24 weeks, versus those without such findings (5.5 [P = .012] or 9.5 letters [P < .001], respectively). Longitudinal modeling for CLS-TA-treated eyes showed that central subfield thickness (CST) reached 90% of maximal improvement by week 3, whereas 90% maximal response in BCVA was not reached until week 9. CLS-TA-treated eyes that showed CST reduction of ≥50 µm at 4 weeks experienced a greater 24-week improvement in BCVA versus those without such an early response (14.6 vs 6.5 letters, P = .006 for difference). CONCLUSIONS: Pretreatment EZ integrity and the presence of central subfield cystoid spaces or subretinal fluid each predict improved therapeutic response to treatment in eyes with NIU. In CLS-TA treated eyes, longitudinal modeling shows CST improvement preceding BCVA improvement.
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Edema Macular , Uveíte , Biomarcadores , Ensaios Clínicos Fase III como Assunto , Estudos de Coortes , Seguimentos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico por imagem , Edema Macular/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Acuidade VisualRESUMO
IMPORTANCE: Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu). OBJECTIVE: To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included. INTERVENTION: Brolucizumab injections. MAIN OUTCOME AND MEASURES: Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors. RESULTS: Of 10â¯654 and 11â¯161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10â¯654 [90.9%] and 10â¯487 of 11â¯161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10â¯487 [68.2%]), and most were from women (6105 of 10â¯654 [57.3%] and 6452 of 11â¯161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10â¯654 eyes) and 2.4% (268 of 11â¯161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10â¯654 eyes and 63 of 11â¯161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events. CONCLUSIONS AND RELEVANCE: The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.
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Degeneração Macular , Vasculite Retiniana , Uveíte , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados , Estudos de Coortes , Atenção à Saúde , Feminino , Humanos , Inflamação/tratamento farmacológico , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Masculino , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , Sistema de Registros , Vasculite Retiniana/tratamento farmacológico , Uveíte/tratamento farmacológico , Acuidade VisualRESUMO
Importance: The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time. Objective: To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic. Design, Setting, and Participants: Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders. Main Outcomes and Measures: Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic. Results: A total of 526â¯536 CPT codes were ascertained: 483â¯313 injections, 19â¯257 lasers or cryotherapy, 14â¯949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95% CI, -6.8 to -3.3 procedures; P < .001), for RD repairs, with a maximal 59.4% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95% CI, -2.7 to -1.4 repairs; P < .001), and for other vitrectomies, with a maximal 84.3% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95% CI, -3.3 to -1.8 other vitrectomies; P < .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment. Conclusions and Relevance: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.
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COVID-19/epidemiologia , SARS-CoV-2 , Cirurgia Vitreorretiniana/estatística & dados numéricos , Estudos Transversais , Serviços Médicos de Emergência , Humanos , Vitrectomia/estatística & dados numéricosRESUMO
PURPOSE: This study evaluated the potential safety, efficacy, and durability advantages of investigational triamcinolone acetonide suspension (CLS-TA; Clearside Biomedical, Alpharetta, GA) administered suprachoroidally in conjunction with intravitreal aflibercept compared with aflibercept monotherapy for treatment of diabetic macular edema (DME). DESIGN: TYBEE was a prospective, controlled, double-masked study. Patients were randomized 1:1 to CLS-TA and aflibercept (active) or aflibercept monotherapy (control), and assessed over 24 weeks. PARTICIPANTS: Treatment-naive DME patients with best-corrected visual acuity (BCVA) of 20 to 70 letters and central subfield retinal thickness (CST) of more than 300 µm. METHODS: Patients in the active group (n = 36) received CLS-TA and aflibercept at baseline and week 12. Patients in the control group (n = 35) received aflibercept at baseline, week 4, week 8, and week 12. To mask both groups, sham suprachoroidal and intravitreal injections were utilized. All patients were eligible to receive aflibercept as needed at weeks 4, 8, 16, and 20 per prespecified criteria. MAIN OUTCOME MEASURE: Mean change in BCVA from baseline. Treatment differences were assessed with a 2-sided significance level of 0.10. RESULTS: Mean BCVA changes from baseline to week 24 were not statistically different in the active and control groups (intention-to-treat [ITT] population: +11.4 letters and +13.8 letters [P = 0.288]; per protocol [PP] population: +12.3 letters and +13.5 letters [P = 0.664]; respectively). Greater improvement in CST was seen in the active versus control group (ITT population: -212.1 µm and -178.6 µm [P = 0.089]; PP population: -226.5 µm and -176.1 µm [P = 0.035]; respectively). Compared with the control group, eyes in the active group received fewer treatments (scheduled plus as-needed treatments averaging 4.6 versus 2.6, respectively). No treatment-related serious adverse events were observed. Ocular adverse events were low for both arms. Cataract events, all assessed as unrelated to treatment, and events of elevated intraocular pressure trended higher in the active group. CONCLUSIONS: CLS-TA administered suprachoroidally in conjunction with intravitreal aflibercept for treatment of DME provides simliar visual benefit at 24 weeks' follow-up compared with aflibercept monotherapy, is well tolerated and shows modest anatomic benefit with potential to reduce treatment burden.
Assuntos
Retinopatia Diabética/tratamento farmacológico , Macula Lutea/patologia , Edema Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Método Duplo-Cego , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto JovemRESUMO
Purpose: This study assessed physician-investigator experience with suprachoroidal (SC) injections, an investigational therapeutic administration technique using a 900 or 1100 µm microneedle to inject drugs into the SC space. Methods: Datasets from six clinical trials across three diseases (noninfectious uveitis; diabetic macula edema, and retinal vein occlusion) were assessed. In addition to a user survey, retrospective correlations were performed between procedural variables (needle length), and demographics, and ocular characteristics. Results: In the user survey, 84% (31/37) of physician-investigators did not perceive the SC injections to be meaningfully more challenging than other ocular injections. For the correlation analysis, the 900 µm needle was used for 71% (412/581) of baseline injections, and switching to the longer needle occured in the remaining 29% of baseline injections. No statistical correlations were found between needle lengths and age, race, disorder, refraction, visual acuity, intraocular pressure, retinal central subfield thickness, or lens status. Patient gender and needle length were statistically associated, with 76% (210/275) versus 66% (202/306) of injections administered with 900 µm needles for female and male gender, respectively. Injection quadrant correlated to needle length with 78% (214/275) of superotemporal quadrant injections administered with 900 µm needles, compared with 65% (73/113) of inferotemporal quadrant injections. Conclusions: Both the user survey and the correlation analysis demonstrated that SC injection is well accepted by physician-investigators, and the two needle lengths accommodate a wide range of anatomic and demographic variables. Translational Relevance: These results, along with the presented ex-vivo endoscopic imaging, suggest that SC injection could be readily adopted in clinical practice for targeted compartmentalized delivery of ocular therapeutics.
Assuntos
Edema Macular , Doenças Retinianas , Oclusão da Veia Retiniana , Corioide , Feminino , Humanos , Masculino , Doenças Retinianas/tratamento farmacológico , Estudos RetrospectivosRESUMO
OBJECTIVES: To report a case of extensive subcutaneous emphysema introduced during vitrectomy while using an advanced feedback-controlled pressurized infusion system. METHODS: Clinical case report of a 56-year-old woman undergoing pars plana vitrectomy for rhegmatogenous retinal detachment of the left eye. The clinical and radiologic findings of the patient's eyes were documented. The mechanisms of feedback-controlled pressurized infusion devices were reviewed to explain the adverse events. A search of PubMed was conducted to look for any similar cases and/or discussion. RESULTS: In this surgical case, vitrectomy was completed with air-fluid exchange and a formed anterior chamber was observed with an estimated pressure of high teens to low 20s by the surgeon. After the undraping, the patient was noted to have severe facial crepitus extending to the clavicles. Immediate chest X-ray was done, followed by computed tomography, confirming orbital and subcutaneous emphysema, as well as the presence of perfluoro-N-octane in the left orbit. CONCLUSION: Integrated pressurized infusion devices using feedback sensors allow for a sophisticated method of maintaining intraocular pressure and globe formation. However, inadvertent or occult globe rupture may lead to disruption of feedback control and subsequent high rates of infusion. As the infused substances exit the site of rupture, they can lead to extensive extraocular gas or fluid accumulation, and we report a case of severe bilateral subcutaneous emphysema as a result.
RESUMO
OBJECTIVE: To investigate the effects of a novel stereotactic radiosurgical system for pars plana delivery of microcollimated x-rays to the retina and determine the retinal radiological dose response and toxicity threshold in a pig model. METHODS: The x-rays were delivered through the pars plana to the maculae of Yucatan miniswine to verify the targeting and safety of a cornea-scleral, stabilized, office-based delivery system. Twelve eyes were randomized to receive 0, 16, 24, 42, 60, or 90 Gy in a single dose to the retina. Eye examinations, fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography were obtained at days 7, 30, 60, and 90. Indocyanine green angiography was done at day 90. RESULTS: Through day 90 interim analysis, no abnormalities of external structures were noted. A small cortical lens opacity was noted in the 60-Gy group. Fundus evaluation revealed no abnormalities at 16 or 24 Gy. Beginning at day 30, circular pale retinal lesions with sharp margins were noted in the maculae of the eyes that received 42, 60, and 90 Gy. Higher-dose lesions showed late staining on fluorescein angiography, choroidal hypoperfusion on indocyanine green angiography, and defined photoreceptor loss and retinal thinning on spectral-domain optical coherence tomography. CONCLUSION: Transscleral stereotactic radiation dosing of porcine eyes demonstrates no apparent clinical abnormalities in doses less than 24 Gy. Doses of 42 Gy or higher led to focal choroidal and retinal damage within the target area. CLINICAL RELEVANCE: Radiation can induce small-blood vessel closure and thereby has therapeutic potential in neovascular diseases such as age-related macular degeneration.
Assuntos
Lesões Experimentais por Radiação/diagnóstico , Retina/efeitos da radiação , Animais , Corantes , Relação Dose-Resposta à Radiação , Angiofluoresceinografia , Verde de Indocianina , Projetos Piloto , Doses de Radiação , Dosagem Radioterapêutica , Retina/patologia , Suínos , Porco Miniatura , Tomografia de Coerência Óptica , Raios XRESUMO
PURPOSE: The purpose of this study was to describe the management of a keratoplasty lenticule adhering to the retina after intraoperative dislocation. METHODS: We describe the posterior dislocation of the donor lenticule during endothelial keratoplasty in a 72-year-old woman with a transscleraly sutured intraocular lens, previous pars plana vitrectomy, and a posteriorly positioned Ahmed glaucoma tube shunt. The lenticule was retrieved through a pars plana approach 2 weeks later, at which time it was tightly adherent to the extramacular retina. Concurrent keratoplasty was performed. RESULTS: Six months after retrieval of the dislocated lenticule with repeat keratoplasty, the retinal examination is stable and the new graft remains attached. CONCLUSION: An iris defect, the absence of capsular support, and a history of previous vitrectomy are all potential risk factors for the intraoperative migration of a keratoplasty lenticule. The surgical view 2 weeks after dislocation was not a limiting factor in the retrieval of the lenticule. However, the tight adherence of the lenticule to the retina required extensive peeling. To avoid a more difficult surgical repair and the potential for scar formation, earlier surgical repair would be preferable, especially if dealing with a macular location.
RESUMO
Cornelia de Lange syndrome (CdLS), a congenital disorder characterized by growth and mental retardation, hirsutism, and skeletal and cardiac anomalies, has been associated with a number of ophthalmic abnormalities including synophrys, long eyelashes, myopia, nasolacrimal duct obstruction, and ptosis. Only one case of Coats' disease has been described in the setting of this syndrome.(1) We describe a second case of Coats' disease in a five-year-old boy with this condition.
Assuntos
Síndrome de Cornélia de Lange/complicações , Anormalidades do Olho/complicações , Disco Óptico/anormalidades , Retinite/complicações , Telangiectasia/complicações , Pré-Escolar , Síndrome de Cornélia de Lange/diagnóstico , Exsudatos e Transudatos , Anormalidades do Olho/diagnóstico , Humanos , Masculino , Retinite/diagnóstico , Telangiectasia/diagnósticoRESUMO
PURPOSE: To study the retinal degeneration in an 11 -year-old patient with Leber congenital amaurosis (LCA) caused by mutation in GUCY2D. STUDY DESIGN: Comparative human tissue study. PARTICIPANTS: Two subjects with LCA; postmortem eye from one LCA patient and three normal donors. METHODS: Clinical and visual function studies were performed between the ages of 6 and 10 years in the LCA eye donor and at age 6 in an affected sibling. Genomic DNA was screened for mutations in known LCA genes. The retina of the 11 -year-old subject with LCA was compared with normal retinas from donors age 3 days, 18 years, and 53 years. The tissues were processed for histopathologic studies and immunofluorescence with retinal cell-specific antibodies. RESULTS: Vision in both siblings at the ages examined was limited to severely impaired cone function. Mutation in the GUCY2D gene was identified in both siblings. Histopathologic study revealed rods and cones without outer segments in the macula and far periphery. The cones formed a monolayer of cell bodies, but the rods were clustered and had sprouted neurites in the periphery. Rods and cones were not identified in the midperipheral retina. The inner nuclear layer appeared normal in thickness throughout the retina, but ganglion cells were reduced in number. CONCLUSIONS: An 11-year-old subject with LCA caused by mutant GUCY2D had only light perception but retained substantial numbers of cones and rods in the macula and far periphery. The finding of numerous photoreceptors at this age may portend well for therapies designed to restore vision at the photoreceptor level.