Intravitreal gas for symptomatic vitreomacular adhesion: a synthesis of the literature

Neffendorf, James E; Simpson, Andrew; Steel, David; Desai, R. M.; McHugh, Dominic; Pringle, Edward; Jackson, Timothy L.

doi:10.1111/aos.13547

Cited by 18 publications

(18 citation statements)

References 45 publications

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“…Overall, the present study shows a potentially useful approach to obtain promising leads based on human Micro-plasmin that may be of clinical use in the near future, especially in thrombolytic therapies for ischemic stroke and also, possibly, intra-ocular applications [78].…”

Section: Discussionmentioning

confidence: 99%

Site-specific PEGylation of micro-plasmin for improved thrombolytic therapy through engineering enhanced resistance against serpin mediated inhibition

2019

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The relatively rapid inhibition of microplasmin by α 2 -AP leads to short functional half-life of the molecule in vivo , causing inefficient clot dissolution, even after site-specific, local catheter-based delivery. Here, we describe a PEGylation approach for improving the therapeutic potential via improving the survival of microplasmin in presence of its cognate inhibitor, α 2 -AP, wherein a series of strategically designed cysteine analogs of micro-plasminogen were prepared and expressed in E . coli , and further modified by covalent grafting in vitro with PEG groups of different molecular sizes so as to select single or double PEG chains that increase the molecular weight and hydrodynamic radii of the conjugates, but with a minimal discernible effect on intrinsic plasmin activity and structural framework, as explored by amidolytic activity and CD-spectroscopy, respectively. Interestingly, some of the purified PEG-coupled proteins after conversion to their corresponding proteolytically active forms were found to exhibit significantly reduced inhibition rates (up to 2-fold) by α 2 -AP relative to that observed with wild-type microplasmin. These results indicate an interesting, and not often observed, effect of PEG groups through reduced/altered dynamics between protease and inhibitor, likely through a steric hindrance mechanism. Thus, the present study successfully identifies single- and double-site PEGylated muteins of microplasmin with significantly enhanced functional half-life through enhanced resistance to inactivation by its in vivo plasma inhibitor. Such an increased survival of bioactivity in situ , holds unmistakable potential for therapeutic exploitation, especially in ischemic strokes where a direct, catheter-based deposition within the cranium has been shown to be promising, but is currently limited by the very short in vivo bioactive half-life of the fibrin dissolving agent/s.

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Section: Discussionmentioning

confidence: 99%

Site-specific PEGylation of micro-plasmin for improved thrombolytic therapy through engineering enhanced resistance against serpin mediated inhibition

2019

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“…This technique seems to be more effective than ocriplasmin injection as a primary treatment for vitreomacular traction, but its use for small macular holes with traction is not yet fully established [17] and a few contraindications to gas injection (mainly air travel and late-stage glaucoma) remain.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Results of Vitrectomy for Macular Holes after Failure of Vitreolysis

Benarous¹,

Y²

2018

Ophthalmologica

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Purpose: Ocriplasmin injection may close some small-to-medium macular holes associated with vitreoretinal traction. If the treatment fails, does vitrectomy and gas injection yield the same results as primary surgery? Material and Methods: We report a retrospective case series study of 3 eyes of 3 consecutive patients operated on a few months after initial intravitreal injection of ocriplasmin and enlargement of the macular hole. The minimal follow-up period after surgery was 18 months. Results: Surgery was uneventful in all cases. Vitrectomy, internal limiting membrane peeling, and gas injection allowed closing of the 3 macular holes with a progressive improvement in visual acuity over time. Before ocriplasmin injection, visual acuity ranged from 20/60 to 20/32, after failed ocriplasmin injection from 20/80 to 20/40, and at the final follow-up after 18 months from 20/32 to 20/25. Conclusion: Vitrectomy with internal limiting membrane peeling leads to closure of macular holes even in cases of prior failure to close them by ocriplasmin injection.

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“…There are three commonly used management options for VMT – observation, vitreolysis and vitrectomy. There are also small clinical case series investigating the use of a gas bubble to treat VMT 14. The current standard of care in early stage VMT is observation, a strategy that is often justified for people with no or few symptoms and in the expectation that some cases may resolve spontaneously.…”

Section: Introductionmentioning

confidence: 99%

<p>Patient-reported outcomes of ocriplasmin for the treatment of vitreomacular traction: a systematic review and synthesis of the literature</p>

Lescrauwaet¹,

Blot²,

Jackson³

2019

PROM

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Purpose Vitreomacular traction (VMT) is a disease in which the vitreous exerts abnormally strong traction on the macula, the area of the eye responsible for detailed central vision. If this traction significantly distorts the macula then VMT can lead to troublesome distorted vision (metamorphopsia), sometimes occurring despite relatively preserved visual acuity. Ocriplasmin, administered as a single intravitreal injection, aims to release VMT and improve vision. While the effect of ocriplasmin on traction release and visual acuity is well characterized, the effect of symptoms like metamorphopsia is not. Methods A systematic review and synthesis of the literature on patient reported outcomes (PRO) in relation to the use of ocriplasmin for the treatment of VMT was undertaken using MED-LINE and Embase databases, and the Cochrane central register of controlled trials (CENTRAL). Results The review identified PRO data from 870 patients across three randomized controlled trials. The most commonly reported PROs were the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25), a broad measure of vision-related quality of life, and Visual Function Response (VFR), an outcome combining quality of life and visual acuity outcomes. Treatment with ocriplasmin produced significant patient benefit vs control (sham or placebo-injection). Ocriplasmin was associated with a higher proportion of patients experiencing a clinically meaningful improvement in visual functioning with a difference of 11.8% for VFQ-25 and 23.2% for VFR responder analyses, respectively. Conclusion Patients with VMT have material impairment in visual functioning and quality of life, relative to their reduction in visual acuity. Ocriplasmin results in a significant improvement in visual functioning. Future research could include the development of new PROs specific to VMT.

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Intravitreal gas for symptomatic vitreomacular adhesion: a synthesis of the literature

Cited by 18 publications

References 45 publications

Site-specific PEGylation of micro-plasmin for improved thrombolytic therapy through engineering enhanced resistance against serpin mediated inhibition

Site-specific PEGylation of micro-plasmin for improved thrombolytic therapy through engineering enhanced resistance against serpin mediated inhibition

Long-Term Results of Vitrectomy for Macular Holes after Failure of Vitreolysis

<p>Patient-reported outcomes of ocriplasmin for the treatment of vitreomacular traction: a systematic review and synthesis of the literature</p>

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