Browsing by Subject "Intravitreal injections"

Now showing 1 - 4 of 4
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    Choice of Dose Level for a Randomized Clinical Trial of Low-Dose Bevacizumab vs Laser for Type 1 Retinopathy of Prematurity
    (American Medical Association, 2021) Kraker, Raymond T.; Wallace, David K.; Beck, Roy W.; Saunders, Christina T.; Lorenzi, Elizabeth; Melia, B. Michele; Li, Zhuokai; Ophthalmology, School of Medicine
    This study determines which of 8 doses of bevacizumab are effective in treating severe retinopathy of prematurity to carry forward to a large-scale randomized clinical trial.
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    Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients
    (Springer Nature, 2024) Pereira, Daniel S.; Maturi, Raj K.; Akita, Kazumasa; Mahesh, Vinaya; Bhisitkul, Robert B.; Nishihata, Toshiaki; Sakota, Eri; Ali, Yusuf; Nakamura, Emiko; Bezwada, Padma; Nakamura, Yoshikazu; Ophthalmology, School of Medicine
    Background/objective: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative age-related macular degeneration (nAMD). Due to the limitations of these standard therapies, targeting alternative mechanisms of action may be helpful for treatment of this very common disease. Here, we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, umedaptanib pegol, a next generation therapeutic for the treatment of nAMD. Methods: Three phase 2 studies were designed. First, a multicentre, randomized, double-masked TOFU study assessed the efficacy of intravitreal injections of umedaptanib pegol monotherapy or in combination with aflibercept, compared to aflibercept monotherapy in 86 subjects with anti-VEGF pretreated nAMD. Second, 22 subjects who had exited the TOFU study received 4 monthly intravitreal injections of umedaptanib pegol (extension, RAMEN study). Third, as an investigator-sponsored trial (TEMPURA study), a single-center, open-label, 4-month study was designed to evaluate the safety and treatment efficacy of umedaptanib pegol in five naïve nAMD patients who had not received any prior anti-VEGF treatment. Results: The TOFU study demonstrated that umedaptanib pegol alone or in combination with aflibercept did not improve best-corrected visual acuity (BCVA) and central subfield thickness (CST) over aflibercept alone. However, the change in BCVA and CST at primary endpoint was marginal in all the three treatment groups, suggesting that umedaptanib pegol is effective to prevent the disease progression. The RAMEN study confirmed the cessation of disease progression. In the TEMPURA study, naïve nAMD patients showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients. Conclusions: These results demonstrate, for the first time, clinical proof of concept for aptamer based anti-FGF2 therapy of nAMD.
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    Plasma Levels of Bevacizumab and Vascular Endothelial Growth Factor After Low-Dose Bevacizumab Treatment for Retinopathy of Prematurity in Infants
    (American Medical Association, 2022) Hartnett, M. Elizabeth; Wallace, David K.; Dean, Trevano W.; Li, Zhuokai; Boente, Charline S.; Dosunmu, Eniolami O.; Freedman, Sharon F.; Golden, Richard P.; Kong, Lingkun; Prakalapakorn, S. Grace; Repka, Michael X.; Smith, Lois E.; Wang, Haibo; Kraker, Raymond T.; Cotter, Susan A.; Holmes, Jonathan M.; Ophthalmology, School of Medicine
    Importance: Intravitreal bevacizumab effectively treats severe retinopathy of prematurity (ROP), but it enters the bloodstream and may reduce serum vascular endothelial growth factor (VEGF), potentially causing detrimental effects on developing organs in the premature infant. Objective: To evaluate the association of intravitreal bevacizumab with plasma bevacizumab and VEGF concentrations at 2 and 4 weeks after predefined, de-escalating doses of intravitreal bevacizumab were administered to infants with severe ROP. Design, setting, and participants: This phase 1 dose de-escalation case series study was conducted at 10 US hospitals of ophthalmology institutions from May 21, 2015, to May 7, 2019. Blood samples were collected 2 and 4 weeks after intravitreal bevacizumab injection. Participants included 83 premature infants with type 1 ROP in 1 or both eyes and no previous ROP treatment. Data were analyzed from April 2017 to August 2021. Interventions: Study eyes received a single bevacizumab injection of 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. When the fellow eye required treatment, one dose higher was administered. Total dose administered at baseline was defined as the sum of doses given to each eye within 3 days of initial study-eye injection. Main outcomes and measures: Plasma bevacizumab concentration at 2 and 4 weeks after injection and the percentage change in plasma VEGF concentrations from pretreatment levels. Results: A total of 83 infants (mean [SD] age, 25 [2] weeks; 48 boys [58%]) were included in this study. Higher doses of bevacizumab administered at baseline were associated with higher plasma bevacizumab concentrations at 2 weeks (ρ, 0.53; 95% CI, 0.31-0.70) and 4 weeks (ρ, 0.44; 95% CI, 0.18-0.64). Plasma VEGF concentrations decreased by 50% or more from pretreatment levels in 40 of 66 infants (61%) at 2 weeks and 31 of 61 infants (51%) at 4 weeks, but no association was observed between the total dose of bevacizumab administered at baseline and percentage change in plasma VEGF concentrations 2 weeks (ρ, -0.04; 95% CI, -0.28 to 0.20) or 4 weeks (ρ, -0.17; 95% CI, -0.41 to 0.08) after injection. Conclusions and relevance: Results of this phase 1 dose de-escalation case series study revealed that bevacizumab doses as low as 0.002 mg were associated with reduced plasma VEGF levels for most infants at 2 and 4 weeks after intravitreal administration; however, no association was observed between total bevacizumab dose administered and reductions in plasma VEGF levels from preinjection to 2 weeks or 4 weeks. Additional studies are needed to evaluate the long-term effects of low-dose bevacizumab on neurodevelopment and retinal structure.
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    Visual acuity outcomes and anti-VEGF therapy intensity in macular oedema due to retinal vein occlusion: a real-world analysis of 15 613 patient eyes
    (BMJ, 2021) Ciulla, Thomas; Pollack, John S.; Williams, David F.; Ophthalmology, School of Medicine
    Background/aims: To assess visual acuity (VA) outcomes and antivascular endothelial growth factor (anti-VEGF) therapy intensity in retinal vein occlusion (RVO)-related macular oedema (ME). Methods: A retrospective study was completed in treatment-naïve patients with RVO-related ME from 2013 to 2019, using the Vestrum Health Retina Database. Results: Mean baseline age was 72.4 years and 54% were women. In 6 months, in 8876 eyes with branch retinal vein occlusion (BRVO)-related ME, after a mean of 4.5 anti-VEGF injections, VA increased by 9.4 letters (95% confidence interval (CI) for change in VA +8.94 to +9.78, p<0.001) from a baseline of 55.1 letters. In 6737 eyes with central retinal vein occlusion (CRVO)-related ME, after a mean of 4.6 anti-VEGF injections over 6 months, VA improved by 9.2 letters (95% CI +8.50 to +9.87, p<0.001) from a baseline of 37.2 letters. In 1 year, VA gain was similar (BRVO: 7.4 injections, +8.1 letters, 95% CI +7.55 to +8.57, p<0.001; CRVO: 7.6 injections, +7.1 letters, 95% CI +6.31 to +7.95, p<0.001). In 6 months and 1 year, mean letters gain increased with number of anti-VEGF injections. Patient eyes with baseline VA of 20/40 or better tended to lose VA in 1 year. Conclusion: Mean change in VA correlates with treatment intensity, but patients with better VA at presentation are susceptible to vision loss, reflecting a ceiling effect. Assessed with the same database, VA gains compare favourably with 1-year VA gains in neovascular age-related macular degeneration and diabetic ME, but exhibit a larger gap when compared with corresponding randomised controlled trials.