Publications by authors named "Ann Yung"

8 Publications

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Development and characterization of a hydrogel-based adhesive patch for sealing open-globe injuries.

Acta Biomater 2022 01 19;137:53-63. Epub 2021 Oct 19.

Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, United States. Electronic address:

Full-thickness wounds to the eye can lead to serious vision impairment. Current standards of care (from suturing to tissue transplantation) usually require highly skilled surgeons and use of an operating theater. In this study, we report the synthesis, optimization, and in vitro and ex vivo testing of photocrosslinkable hydrogel-based adhesive patches that can easily be applied to globe injuries or corneal incisions. According to the type and concentration of polymers used in the adhesive formulations, we were able to finely tune the physical properties of the bioadhesive including viscosity, elastic modulus, extensibility, ultimate tensile strength, adhesion, transparency, water content, degradation time, and swellability. Our in vitro studies showed no sign of cytotoxicity of the hydrogels. Moreover, the hydrogel patches showed higher adhesion on freshly explanted pig eyeballs compared to a marketed ocular sealant. Finally, ex vivo feasibility studies showed that the hydrogel patches could seal complex open-globe injuries such as large incision, cruciform injury, and injury associated with tissue loss. These results suggest that our photocrosslinkable hydrogel patch could represent a promising solution for the sealing of open-globe injuries or surgical incisions. STATEMENT OF SIGNIFICANCE: Current management of severe ocular injuries require advanced surgical skills and access to an operating theater. To address the need for emergent management of wounds that cannot be handled in the operating room, surgical adhesives have gained popularity, but none of the currently available adhesives have optimal bioavailability, adhesive or mechanical properties. This study describes the development, optimization and testing of a light-sensitive adhesive patch that can easily be applied to the eye. After solidification using visible light, the patch shows no toxicity and is more adherent to the tissue than a marketed sealant. Thus this technology could represent a promising solution to stabilize ocular injuries in emergency settings before definitive surgical repair.
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http://dx.doi.org/10.1016/j.actbio.2021.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678346PMC
January 2022

Ocular redness - I: Etiology, pathogenesis, and assessment of conjunctival hyperemia.

Ocul Surf 2021 07 16;21:134-144. Epub 2021 May 16.

Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:

The translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation of the conjunctival microvasculature consisting of extensive branching of superficial and deep arterial systems and corresponding drainage pathways, and the translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation. Conjunctival hyperemia is caused by a pathological vasodilatory response of the microvasculature in response to inflammation due to a myriad of infectious and non-infectious etiologies. It is one of the most common contributors of ocular complaints that prompts visits to medical centers. Our understanding of these neurogenic and immune-mediated pathways has progressed over time and has played a critical role in developing targeted novel therapies. Due to a multitude of underlying etiologies, patients must be accurately diagnosed for efficacious management of conjunctival hyperemia. The diagnostic techniques used for the grading of conjunctival hyperemia have also evolved from descriptive and subjective grading scales to more reliable computer-based objective grading scales.
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http://dx.doi.org/10.1016/j.jtos.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328962PMC
July 2021

Ocular redness - II: Progress in development of therapeutics for the management of conjunctival hyperemia.

Ocul Surf 2021 07 15;21:66-77. Epub 2021 May 15.

Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:

Conjunctival hyperemia is one of the most common causes for visits to primary care physicians, optometrists, ophthalmologists, and emergency rooms. Despite its high incidence, the treatment options for patients with conjunctival hyperemia are restricted to over-the-counter drugs that provide symptomatic relief due to short duration of action, tachyphylaxis and rebound redness. As our understanding of the immunopathological pathways causing conjunctival hyperemia expands, newer therapeutic targets are being discovered. These insights have also contributed to the development of animal models for mimicking the pathogenic changes in microvasculature causing hyperemia. Furthermore, this progress has catalyzed the development of novel therapeutics that provide efficacious, long-term relief from conjunctival hyperemia with minimal adverse effects.
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http://dx.doi.org/10.1016/j.jtos.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328932PMC
July 2021

Growth factor-eluting hydrogels for management of corneal defects.

Mater Sci Eng C Mater Biol Appl 2021 Jan 10;120:111790. Epub 2020 Dec 10.

Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, United States. Electronic address:

With 1.5-2.0 million new cases annually worldwide, corneal injury represents a common cause of vision loss, often from irreversible scarring due to surface corneal defects. In this study, we assessed the use of hepatocyte growth factor (HGF) loaded into an in situ photopolymerizable transparent gelatin-based hydrogel for the management of corneal defects. In vitro release kinetics showed that, in regard to the total amount of HGF released over a month, 55 ± 11% was released during the first 24 h, followed by a slow release profile for up to one month. The effect of HGF was assessed using an ex vivo model of pig corneal defect. After three days of organ culture, epithelial defects were found to be completely healed for 89% of the corneas treated with HGF, compared to only 11% of the corneas that had fully re-epithelialized when treated with the hydrogel without HGF. The thickness of the epithelial layer was found to be significantly higher for the HGF-treated group compared to the group treated with hydrogel without HGF (p = 0.0012). Finally, histological and immunostaining assessments demonstrated a better stratification and adhesion of the epithelial layer in the presence of HGF. These results suggest that the HGF-loaded hydrogel system represents a promising solution for the treatment of persistent corneal defects at risk of scarring.
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http://dx.doi.org/10.1016/j.msec.2020.111790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867677PMC
January 2021

Ciprofloxacin-loaded bioadhesive hydrogels for ocular applications.

Biomater Sci 2020 Sep;8(18):5196-5209

Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA and Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

The management of corneal infections often requires complex therapeutic regimens involving the prolonged and high-frequency application of antibiotics that provide many challenges to patients and impact compliance with the therapeutic regimens. In the context of severe injuries that lead to tissue defects (e.g. corneal lacerations) topical drug regimens are inadequate and suturing is often indicated. There is thus an unmet need for interventions that can provide tissue closure while concurrently preventing or treating infection. In this study, we describe the development of an antibacterial bioadhesive hydrogel loaded with micelles containing ciprofloxacin (CPX) for the management of corneal injuries at risk of infection. The in vitro release profile showed that the hydrogel system can release CPX, a broad-spectrum antibacterial drug, for up to 24 h. Moreover, the developed CPX-loaded hydrogels exhibited excellent antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa, two bacterial strains responsible for the most ocular infections. Physical characterization, as well as adhesion and cytocompatibility tests, were performed to assess the effect of CPX loading in the developed hydrogel. Results showed that CPX loading did not affect stiffness, adhesive properties, or cytocompatibility of hydrogels. The efficiency of the antibacterial hydrogel was assessed using an ex vivo model of infectious pig corneal injury. Corneal tissues treated with the antibacterial hydrogel showed a significant decrease in bacterial colony-forming units (CFU) and a higher corneal epithelial viability after 24 h as compared to non-treated corneas and corneas treated with hydrogel without CPX. These results suggest that the developed adhesive hydrogel system presents a promising suture-free solution to seal corneal wounds while preventing infection.
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http://dx.doi.org/10.1039/d0bm00935kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594650PMC
September 2020

Efficacy of cyanoacrylate tissue adhesive in the management of corneal thinning and perforation due to microbial keratitis.

Ocul Surf 2020 10 19;18(4):795-800. Epub 2020 Aug 19.

Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA. Electronic address:

Purpose: Report the efficacy of cyanoacrylate tissue adhesive (CTA) application in the management of corneal thinning and perforations associated with microbial keratitis.

Methods: A retrospective review of consecutive patients who underwent CTA application for corneal thinning and perforation secondary to microbiologically proven infectious keratitis between 2001 and 2018 at a single center. We defined successful CTA application as an intact globe without tectonic surgical intervention.

Results: The cohort included 67 patients, and 37 presented with corneal perforation while 30 had corneal thinning. The perforation/thinning was central/paracentral in 43 eyes and peripheral in 23 eyes. The underlying infectious etiologies were monomicrobial in 42 cases (35 bacterial, 3 fungal, 2 viral, and 2 acanthamoeba cases) and polymicrobial in 25 cases (22 polybacterial cases and 3 cases with a combination of Gram positive bacteria and fungus). The median duration of glue retention was 29 days. The CTA success rate was 73%, 64%, and 44% at 10, 30, and 180 days, respectively. CTA application appears more successful in monomicrobial (vs. polymicrobial) and Gram positive bacterial (vs. Gram negative) keratitis but the differences are statistically non-significant. The location of perforation/thinning and the use of topical corticosteroid were not associated with CTA failure.

Conclusion: CTA was moderately effective in restoring globe integrity in severe corneal thinning and perforation secondary to microbial keratitis in the short term. However the majority of patients require tectonic surgical intervention within 6 months. CTA application success is not significantly associated with the location of thinning/perforation or the use of topical corticosteroid.
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http://dx.doi.org/10.1016/j.jtos.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686147PMC
October 2020

Efficacy and retention of silicone punctal plugs for treatment of dry eye in patients with and without ocular graft-versus-host-disease.

Ocul Surf 2020 10 30;18(4):731-735. Epub 2020 Jul 30.

Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA. Electronic address:

Purpose: To examine the retention rates and efficacy of silicone punctal plugs for the treatment of dry eye disease (DED) in patients with ocular graft-versus-host-disease (oGVHD) in comparison to dry eye disease due to non-oGVHD etiologies.

Methods: We reviewed the case-records of 864 consecutive patients with DED who were symptomatic despite topical therapy and had silicone punctal plugs placed over an eight-year- period at a single academic center. We compared plug retention rates in oGVHD and non-oGVHD DED patients using Kaplan-Meier analyses. Furthermore, we analyzed changes in objective ocular surface parameters including tear breakup time (TBUT), Schirmer's test, and corneal fluorescein staining (CFS) score in plug-retaining patients at two-, six- and twelve-month follow-up.

Results: Median age of dry eye patients was 58 years, and 606 (70%) of patients were women. In the cohort, 264 (31%) patients were diagnosed with oGVHD. Plug retention was significantly lower in oGVHD-DED patients compared to non-oGVHD-DED patients (p < 0.0001). We observed significant improvement in CFS scores in plug retaining-oGVHD and non-oGVHD DED patients at all time points. Tear break-up time was significantly prolonged at six- and twelve-months follow-up in non-oGVHD patients, whereas significant change in TBUT in oGVHD patients was recorded only at twelve months post plug placement. Schirmer's score improved significantly in plug retaining-non-oGVHD DED patients at six- and twelve-months follow-up, however no significant change was observed in Schirmer's score in oGVHD DED patients.

Conclusions: An improvement in ocular surface disease parameters was observed in both plug-retaining oGVHD and non-oGVHD DED patients. However, a majority of oGVHD DED patients spontaneously lost their punctal plugs within 90 days of placement. Therefore, regular follow-up after plug placement is recommended to detect plug loss and ensure adequate disease control.
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http://dx.doi.org/10.1016/j.jtos.2020.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686277PMC
October 2020

Outcomes of Cyanoacrylate Tissue Adhesive Application in Corneal Thinning and Perforation.

Cornea 2019 Jun;38(6):668-673

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.

Purpose: To report the outcomes of cyanoacrylate tissue adhesive (CTA) application in corneal thinning and perforation.

Methods: A retrospective interventional case series of 137 patients receiving CTA for corneal thinning and perforation in 140 eyes between 2001 and 2018 at a single center was reviewed. Success rate and factors associated with glue failure were analyzed.

Results: Median age of the cohort was 63 years and 69 (50%) were women. One hundred fifteen patients (84%) had at least 1 systemic condition, 46 (34%) had autoimmune diseases. Eighty-nine eyes (64%) presented with perforation and 51 (36%) with thinning. The perforation/thinning was central/paracentral in 82 eyes (59%) and peripheral in 57 eyes (41%). Median size of perforation was 3.1 mm. Causes of perforation and thinning were microbial infection in 75 (55%), sterile melt in 49 (35%), laceration in 10, and keratoprosthesis melt in 8 eyes. Median glue retention was 58 days. Success rate of glue application (defined as intact globe without surgical intervention) was 72%, 61%, and 46% at 10, 30, and 90 days after glue application, respectively. Larger size of perforation/thinning, perforation (vs. thinning), and single glue application (vs. multiple) were correlated with higher failure rate. Systemic conditions, use of topical corticosteroid, etiologies, and location of perforation/thinning were not significantly correlated with glue failure.

Conclusions: CTA application was moderately effective in stabilizing corneal perforation and thinning in the very short-term. Multiple applications are often required. Maintenance of globe integrity after glue application decreases with time and the need for surgical intervention remains high.
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http://dx.doi.org/10.1097/ICO.0000000000001919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517072PMC
June 2019
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