Intravitreal injection of polysorbate 80: a functional and morphological study

Damico, Francisco Max; Gasparin, Fabio; Ioshimoto, Gabriela Lourençon; Igami, Thais Zamudio; Silva-Cunha, Armando; Fialho, Sílvia Ligório; Liber, Andre; Young, Lucy H.; Ventura, Dora Fix

doi:10.1590/0100-69912017006010

Cited by 7 publications

(4 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, PEG-interferon-associated retinopathy usually develops bilaterally, without symptoms, 2–6 months after treatment commences, whereas our patients were predominantly unilateral and symptomatic, and developed disease within 21 days of vaccination. Furthermore, unlike the BNT162b2 vaccine, ChAdOx1 nCoV-19 is not an mRNA vaccine; rather, it is an adenovirus-vectored vaccine that includes polysorbate 80 as an excipient; this material appears to be safe even when directly injected into the vitreous cavity [ 31 ]. RVO and submacular hemorrhage also developed after ChAdOx1 vaccination.…”

Section: Discussionmentioning

confidence: 99%

Retinal Hemorrhage after SARS-CoV-2 Vaccination

Park

Byun²,

Byeon

et al. 2021

JCM

View full text Add to dashboard Cite

To report retinal vein occlusion (RVO) and age-related macular degeneration (AMD)-related submacular hemorrhage developing after administration of SARS-CoV-2 vaccines, a single-center, retrospective observational case series was conducted. Clinical data including fundus photographs and optical coherence tomography (OCT) scans were reviewed. Twenty-three eyes of 21 patients were included with the median age at symptom presentation being 77 years (range: 51–85 years). Twelve eyes (52.2%) had submacular hemorrhage and 11 (47.8%) had RVO. Twelve patients (60.9%) had been vaccinated with the Pfizer vaccine (BNT162b2) and 8 with the AstraZeneca (ChAdOx1) vaccine. Sixteen patients (76.2%) experienced ocular disease exacerbation after the first vaccination and 4 (19.0%) after the second vaccination. The median visual acuity (logarithm of the minimal angle of resolution; logMAR) before symptom development was 0.76 (interquartile range: 0.27–1.23); the median logMAR at symptom presentation was 1.40 (interquartile range 0.52–1.70). The median time between vaccination and symptom exacerbation was 2.0 days (interquartile range: 1.0–3.0 days). Five patients (23.8%) underwent tests for hematological abnormalities, including the presence of anti-PF4 antibodies; all were negative. Further studies with larger patient group for evaluation of effect of SARS-CoV-2 vaccination on retinal hemorrhage are necessary.

show abstract

Section: Discussionmentioning

confidence: 99%

Retinal Hemorrhage after SARS-CoV-2 Vaccination

Park

Byun²,

Byeon

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…Histidine and histidine hydrochloride monohydrate are already tested for IVT route and approved for human diseases as an anti-VEGF drug [42]. Damico et al showed that IVT injection of polysorbate 80 in the concentration for IVT drug preparations did not cause any functional alterations of rabbit retinas [43]. In human eye, vitreous humor is approximately 4 mL, while volume of the rabbit vitreous is approximately 1.5 mL.…”

Section: Discussionmentioning

confidence: 99%

Ocular toxicity of intravitreal golimumab in a rabbit model

Engin¹,

Mıçılı²,

Yılmaz³

et al. 2020

Turk J Med Sci

View full text Add to dashboard Cite

Background/aim: To investigate the effect of intravitreal golimumab on rabbit retina histopathology. Materials and methods: Sixteen albino New Zealand rabbits were divided into three groups. The right eye of each rabbit in groups I, II, and III received a single intravitreal injection of 5 mg/0.05 mL (6 eyes), 10 mg/0.1 mL (6 eyes), or 20 mg/0.2 mL (4 eyes) golimumab, while left eyes served as controls with the same volume of a balanced salt solution injection. All animals were examined using slit-lamp biomicroscopy and indirect ophthalmoscopy before and after intravitreal injection and at days 1 and 7. Animals were euthanized on day 7 and the eyes were enucleated for immunohistochemistry evaluation and electron microscopic examination of the retinas. Results: For groups I, II, and III, the number of cells in the outer nuclear layer and the inner nuclear layer was decreased compared to those in the control groups. In group I, the percentage of caspase-3 staining of the outer nuclear layer was significantly higher than that in the control. For groups II and III, TUNEL and caspase-3 staining percentages in the outer and inner nuclear layers were found to be significantly higher than those for the control groups. In the ganglion cell layer, for groups I, II, and III, neither TUNEL nor caspase-3 staining percentages showed any significant difference between two groups. No significant dose-dependent relationship was found for increasing doses of golimumab in all layers. Myelin figures and karyorrhexis in the photoreceptor cells were prominent in electron microscopy of the golimumab-injected eyes. Conclusion: Golimumab caused apoptosis in both photoreceptors and bipolar cells of the rabbit retina. Potential retinal toxicity of intravitreal golimumab should be considered if an intravitreal administration is planned.

show abstract

“…[6][7][8][9] They are also commonly used to assess direct retinal toxicities that may be associated with formulation pH and excipients. [10][11][12][13] In various studies, direct retinal toxicities arising from intravitreal formulations are commonly observed in rabbit eyes as early as 3 days. [10][11][12][13] In this study, all eyes were observed up to 3 days and evaluation was extended to 9 days for 2 animals that were administered the test article with the lowest pH (pH 4.0) to capture any delayed effects as this solution is expected to shift vitreal pH the most among those evaluated in this study.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13] In various studies, direct retinal toxicities arising from intravitreal formulations are commonly observed in rabbit eyes as early as 3 days. [10][11][12][13] In this study, all eyes were observed up to 3 days and evaluation was extended to 9 days for 2 animals that were administered the test article with the lowest pH (pH 4.0) to capture any delayed effects as this solution is expected to shift vitreal pH the most among those evaluated in this study. No test article-related gross or microscopic findings were observed in any eye at Day 3 or Day 9.…”

Section: Discussionmentioning

confidence: 99%

Tolerability Assessment of Formulation pH in New Zealand White Rabbits Following Intravitreal Administration

Tassew¹,

Laing²,

Aaronson³

et al. 2020

Toxicol Pathol

View full text Add to dashboard Cite

Development of intravitreal drugs presents several challenges due to the delicate ocular environment and volume constraints of what can be safely administered in the eye. Formulation development of intravitreally administered drugs may necessitate the use of nonphysiological pH in order to accommodate manufacturing processes or achieve favorable drug properties. Clinical and nonclinical data show that intravitreal drugs formulated in the pH 5.5 to 7.4 range are well tolerated. The aim of this study was to provide ocular toxicity data for formulations in the pH 4.0 to 5.5 range following intravitreal administration in New Zealand White rabbits. This range was evaluated as part of formulation development for an intravitreal drug that necessitated the use of pH outside the available tolerability data for formulations. Toxicity was assessed by ophthalmic examinations, intraocular pressure (IOP) measurement, clinical observations, body weights, and microscopic analysis of ocular tissue. Histidine chloride pH 5.0 to 5.5 and acetate chloride pH 4.0 to 5.0 solutions were well tolerated, and no test article-related ocular inflammation, IOP changes, or gross or microscopic findings were observed in any eye. The data presented here add to the knowledge of pH ranges that can be explored for intravitreal drug formulation development.

show abstract

Intravitreal injection of polysorbate 80: a functional and morphological study

Cited by 7 publications

References 31 publications

Retinal Hemorrhage after SARS-CoV-2 Vaccination

Retinal Hemorrhage after SARS-CoV-2 Vaccination

Ocular toxicity of intravitreal golimumab in a rabbit model

Tolerability Assessment of Formulation pH in New Zealand White Rabbits Following Intravitreal Administration

Contact Info

Product

Resources

About