Outflow Enhancement by Three Different ab Interno Trabeculectomy Procedures in a Porcine Anterior Segment Model

Dang, Yalong; Wang, Chao; Shah, Priyal; Waxman, Susannah; Loewen, Ralitsa T.; Hong, Yuling; Esfandiari, Hamed; Loewen, Nils A.

doi:10.20944/preprints201802.0028.v1

Cited by 6 publications

(10 citation statements)

References 27 publications

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“…Both increased age and reduced TM cellularity are a major risk factor for the development of glaucoma. On the other hand, partially removing TM cells can also reduce IOP at least temporarily 47 , while excision of TM causes a profound and lasting IOP drop ex vivo 27,48 and clinically 49 . Abu-Hassan et al 23 recently showed that the transplantation of human TM cells or TM-like iPSCs into the anterior segment perfusion model can restore outflow after killing about 1/3rd of TM cells with saponin.…”

Section: Discussionmentioning

confidence: 99%

“…Ex vivo perfused anterior segment models from a range of species have been used to examine and manipulate the TM function [20][21][22][23][24][25][26] because there is a scarcity of whole human donor eyes for research. In contrast, TM cells from corneal rims used for corneal transplantation, TM-removal surgeries, and TM cell lines, are more readily available 27,28 and could lend themselves to scalable studies when seeded into decellularized anterior segment scaffolds from pig eyes. As done in other tissues in research [29][30][31][32][33][34] and medical applications [35][36][37][38] , removal of cells from ECM can provide a bioartificial scaffold for recellularization with cells of choice.…”

Section: Introductionmentioning

confidence: 99%

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Tissue-Engineered Anterior Segment Eye Cultures Maintain Intraocular Pressure

Waxman¹,

Wang²,

Dang³

et al. 2020

Preprint

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Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye’s anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM) at the entrance of the eye’s drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered anterior segment eye culture model. We hypothesized that repopulation of a decellularized TM with non-native TM cells could restore aspects of normal TM. The decellularization protocol removed all cells and debris while preserving the ECM. Seeded cells localized to the TM region and progressively infiltrated the meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After a perfusion rate increase challenge, tissue-engineered cultures reestablished normal IOPs (reseeded = 13.7±0.4 mmHg, decellularized = 35.2±2.2 mmHg, p < 0.0001). eGFP expressing CrFK control cells caused a high and unstable IOP (27.0±6.2 mmHg). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. Tissue-engineered organs demonstrated similarities to native tissues and may reduce the need for scarce donor globes in outflow research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tissue-Engineered Anterior Segment Eye Cultures Maintain Intraocular Pressure

Waxman¹,

Wang²,

Dang³

et al. 2020

Preprint

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“…In theory, the IOP that AIT can achieve is limited by the episcleral venous pressure of 8 mmHg [17], yet most studies report IOPs around 15 mmHg. In contrast, TRAB can achieve very low IOPs, even below episcleral venous pressure, and eliminate drops [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Exact Matching of Trabectome-Mediated Ab Interno Trabeculectomy to Conventional Trabeculectomy with Mitomycin C Followed for Two Years

Strzalkowska

Strzalkowski

Yousef

et al. 2020

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Purpose: We used exact matching for a highly balanced comparison of ab interno trabeculectomy (AIT) with the trabectome to trabeculectomy with mitomycin C (TRAB). Methods: 5485 patients who underwent AIT were exact-matched to 196 TRAB patients by baseline intraocular pressure (IOP), number of glaucoma medications, and glaucoma type. Nearest-neighbor-matching was applied to age. Success was defined as a final IOP of less than 21 mmHg, IOP reduction of at least 20% reduction from baseline, and no secondary surgical interventions. Outcomes were measured at 1, 3, 6, 12, 18, and 24 months. Results: 165 AIT could be matched to 165 TRAB. The mean baseline IOP was 22.3+/-5.6 mmHg, and the baseline number of glaucoma medications was 2.7+/-1.1 in both groups. At 24 months, IOP was reduced to 15.8+/-5.2 mmHg in AIT and 12.4+/-4.7 mmHg in TRAB. IOP was lower than baseline at all visits (p<0.01) and lower in TRAB than AIT (p<0.01). Glaucoma medications were reduced to 2.1 +/- 1.3 in AIT and 0.2 +/- 0.8 in TRAB. Compared to baseline, patients used fewer drops postoperatively (p<0.01) and more infrequently in TRAB than in AIT (p>0.01). Secondary surgical interventions had the highest impact on success and became necessary in 15 AIT and 59 TRAB patients. Thirty-two challenging events occurred in TRAB and none in AIT. Conclusion: Both AIT and TRAB reduced IOP and medications. This reduction was more significant in TRAB but at the expense of four times as many secondary interventions.

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“…16,17 The advantages of a clear angle view and anterior chamber stability have recently become more readily available with an I&A-equipped dual-blade (Goniotome, Neomedix Corp., Tustin, California, United States) that does not require a high-frequency generator to molecularize the TM and instead excises a strip. 14,18 These features and its ability to excise TM in a controlled environment and to harvest it non-destructively make it also useful for glaucoma research.…”

Section: Introductionmentioning

confidence: 99%

“…19 In the present study, we hypothesized that trabecular excision with an I&A-equipped dual-blade device could also restore outflow by removing the pathology. We have extensive experience studying outflow in experimental systems, 20,21 including gene transfer, [22][23][24][25][26][27][28] disease modeling 5,7,19 and surgical outflow enhancement, 14,15,18,[29][30][31][32] but this is the first study of a microsurgical intervention for glaucoma in an ex vivo model of glaucoma.…”

Section: Introductionmentioning

confidence: 99%

Intraocular Pressure Reduction in a Pigmentary Glaucoma Model by Goniotome Ab Interno Trabeculectomy

Wang

Dang

Shah

et al. 2018

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Purpose: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. Methods: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, an additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. Results: After the first 90° TM excision, IOP was significantly lower in G (10.23±2.39 mmHg, n=7) than C (20.04±1.97mmHg, n=8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n=7) was significantly lower than C (20.25±1.66 mmHg, n=8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n=7) was higher than C (0.16±0.01 µl/min/mmHg, n=8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P=0.20) or outflow facility (P=0.17) further. Conclusion: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility. Translational Relevance: Microsurgical TM excision over 90° can effectively restore outflow in pigmentary glaucoma.

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Outflow Enhancement by Three Different ab Interno Trabeculectomy Procedures in a Porcine Anterior Segment Model

Cited by 6 publications

References 27 publications

Tissue-Engineered Anterior Segment Eye Cultures Maintain Intraocular Pressure

Tissue-Engineered Anterior Segment Eye Cultures Maintain Intraocular Pressure

Exact Matching of Trabectome-Mediated Ab Interno Trabeculectomy to Conventional Trabeculectomy with Mitomycin C Followed for Two Years

Intraocular Pressure Reduction in a Pigmentary Glaucoma Model by Goniotome Ab Interno Trabeculectomy

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