Scheffer C G Tseng

TissueTech, Inc. · R&D Department

Purpose: Human corneal endothelial cells (HCECs) play a significant role in maintaining visual function. However, these cells are notorious for their limited proliferative capacity in vivo. Current treatment of corneal endothelial dysfunction resorts to corneal transplantation. Herein we describe an ex vivo engineering method to manufacture HCEC g...

PURPOSE: To assess the extent of inferior fornix shortening in conjunctivochalasis (CCh) and to evaluate whether fornix deepening reconstruction can restore the fornix tear reservoir in patients with CCh. MATERIALS AND METHODS: This was a retrospective review of five patients (3 unilateral and 2 bilateral eyes, total 7 eyes) with CCh who underwent...

Purpose To report a successful treatment of chronic rosacea associated ocular demodicosis with lid scrub containing terpinen-4-ol (T4O). Observations A 72-year old woman presented with recurrent and refractory ocular erythema, irritation, dryness, and photophobia despite conventional medical treatment (artificial tears, hypochlorous acid lid hygie...

The trabecular meshwork (TM) is composed of TM cells and beams of the extracellular matrix, together contributing to aqueous humor (AH) outflow resistance. Herein, we validated that our culture system on 2D Matrigel expressed putative TM markers and myocilin, of which the latter was upregulated by dexamethasone. Continuous passage of these cells on...

Pterygium is characterized by encroachment of an abnormal fibrovascular tissue from the bulbar conjunctiva onto the cornea (Arch Ophthalmol 115:1235–1240, 1997). Upon reaching the corneal surface, this fibrovascular tissue exerts cicatricial traction that flattens the caruncle and obliterates the semilunar fold (Arch Ophthalmol 130:39–49, 2012). Th...

Conjunctivochalasis (CCh) presents as loose and redundant conjunctival folds interspersed between the globe and eyelids (Surv Ophthalmol 43:225–232, 1998) and may cause a variety of ocular symptoms that mimic dry eye (Br J Ophthalmol 88:388–392, 2004). CCh disturbs the preocular tear film by blocking the tear drainage, disrupting the tear meniscus,...

Salzmann’s nodular degeneration is a progressive degenerative disease of the cornea that is characterized by the multiple nodular bluish-gray opacities with various number and size (Z Augenheilkd 57:92–99, 1925). The indications for surgery include reduced vision due to encroachment on the visual axis, irregular astigmatism, chronic irritation, and...

Quiescence and self-renewal of human corneal epithelial progenitor/stem cells (LEPC) are regulated by the limbal niche, presumably through close interaction with limbal (stromal) niche cells (LNC). Paired box homeotic gene 6 (Pax6), a conserved transcription factor essential for eye development, is essential for proper differentiation of limbal and...

Homeostasis of the corneal epithelium is ultimately maintained by stem cells that reside in a specialized microenvironment within the corneal limbus termed palisades of Vogt. This limbal niche nourishes, protects, and regulates quiescence, self-renewal, and fate decision of limbal epithelial stem/progenitor cells (LEPCs) toward corneal epithelial d...

Purpose: Fibrosis or scarring is a pathological outcome of wound healing and is characterized by terminally differentiated myofibroblasts. Heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) is a unique matrix component purified from amniotic membrane that exerts an anti-inflammatory effect. Herein, we investigate whether HC-HA/PTX3 can also exer...

An open label, multicenter 16‐week trial of cryopreserved human umbilical cord (TTAX01) was previously undertaken in 32 subjects presenting with a Wagner grade 3 or 4 diabetic foot ulcer, with 16 (50%) of these having confirmed closure following a median of one product application (previous study). All but two subjects (30/32; 94%) consented to par...

Purpose To evaluate the clinical outcomes of self-retained cryopreserved amniotic membrane (cAM) for the treatment of corneal ulcers. Methods This was a single-center, retrospective review of consecutive patients with non-healing corneal ulcers that underwent treatment with self-retained cAM (PROKERA® Slim). The primary outcome measure was time to...

Neurotrophic keratitis (NK), a degenerative disease caused by damage to the trigeminal nerve, abolishes both tearing and blinking reflexes, thus causing the most severe forms of dry eye disease (DED). Conversely, the increasing severity of DED also leads to progressive loss of corneal nerve density, potentially resulting in NK. Both diseases manife...

The birth tissue is predominantly comprised of amniotic membrane (AM) and umbilical cord (UC), which share the same cell origin as the fetus. These versatile biological tissues have been used to treat a wide range of conjunctival and corneal conditions since 1940. The therapeutic benefits of the birth tissue stem from its anti-inflammatory and anti...

OBJECTIVE Despite significant improvement in spinal cord function after in utero spina bifida (SB) repair compared with traditional postnatal repair, over half of the children who undergo this procedure do not benefit completely. This lack of benefit has been attributed to closure methods of the defect, with subsequent spinal cord tethering at the...

Clinical trials of potential new therapies for diabetic foot ulcers rarely enroll patients whose wounds extend to muscle, fascia, or bone with clinical and radiographic evidence of underlying osteomyelitis. An open label, multicenter trial of cryopreserved human umbilical cord (TTAX01) was undertaken in 32 subjects presenting with such complex woun...

On ocular surface, corneal epithelial stem cells (SC) reside in limbus between cornea and conjunctiva. Pax6, an evolutionally conserved transcription factor essential for eye development, is expressed in post-natal corneal and limbal epithelia progenitors (LEPC) but not in underlying stroma. Because Pax6 is transiently expressed in developing corne...

Objective Microbial infection has been reported to cause blepharitis, conjunctivitis and keratitis. We evaluated the safety and efficacy of a foam formulation of 2% 4-terpineol (T4O) against common ocular microorganisms. Material and methods The antimicrobial effect of a 2% T4O formulation was evaluated by the United States Pharmacopeia 51 (USP <5...

To expand multi-potent progenitors from human trabecular meshwork (TM), we have created a new optimized method on two-dimensional (2D) followed by three-dimensional (3D) Matrigel in modified embryonic stem cell medium supplemented with 5% fetal bovine serum (MESCM + 5% FBS). The expanded TM cells were small cuboidal cells expressing TM markers such...

Conjunctivo chalasis (CCh) presents as loose and redundant conjunctival folds interspersed between the globe and eyelids and may cause a variety of ocular symptoms that mimic dry eye. It disturbs the preocular tear film by blocking the tear drainage, disrupting the tear meniscus, and obliterating the fornix tear reservoir to interfere tear flow fro...

Descemet’s membrane (DM) helps maintain phenotype and function of corneal endothelial cells under physiological conditions, while little is known about the function of DM in corneal endothelial wound healing process. In the current study, we performed in vivo rabbit corneal endothelial cell (CEC) injury via CEC scraping, in which DM remained intact...

Purpose: To present a case of successful treatment of immune-related severe dry eye disease (DED) by self-retained cryopreserved amniotic membrane (CAM) in conjunction with conventional and systemic immunotherapy. Observations: A 48-year-old female with a 10-year history of rheumatoid arthritis under systemic immunomodulation developed non-resol...

Aims: To report the clinical characteristics and correlation between meibomian gland dysfunction (MGD) and keratitis in young patients with ocular demodicosis. Methods: Observational case series of 60 patients younger than 35 years with ocular demodicosis, of which the diagnosis was based on microscopic counting of Demodex folliculorum and D. br...

Among different species of mites, Demodex folliculorum and Demodex brevis are the only 2 that affect the human eye. Because demodicosis is highly age-dependent and can be found in asymptomatic adults, the pathogenicity of these mites has long been debated. In this study, we summarize our research experience including our most recent study regarding...

Purpose: To evaluate the therapeutic benefit of self-retained cryopreserved amniotic membrane in conjunction with oral antiviral therapy in herpetic epithelial keratitis. Methods: Retrospective review of 4 patients with primary (1 eye) and recurrent (3 eyes) unilateral herpetic epithelial keratitis treated with cryopreserved amniotic membrane th...

Purpose To determine the prevalence and clinical characteristics of trigeminal–cervical (TC) ocular referred pain. Methods A retrospective study of 1,680 patients seen during 2002–2010 was performed in an ocular surface specialty center to identify patients with or without TC pain defined as ocular pain with ipsilateral trigger points located at t...

Purpose: To report the outcome of self-retained amniotic membrane after debridement in recurrent dendritic keratitis. Observations: A 70-year-old female with a recurrent dendritic corneal ulcer received debridement followed by placement of self-retained amniotic membrane. Five days after treatment, the patient experienced a complete resolution of s...

This book provides residents with a comprehensive review of surgical cases within the field of ophthalmology. Operative Dictations in Ophthalmology touches on important steps within each surgical case, indications for the procedure, possible complications, and a sample dictation. The review serves as both a preparation and debriefing for each surge...

Conjunctivochalasis (CCh) presents as loose and redundant conjunctival folds interspersed between the globe and eyelids (Surv Ophthalmol 43:225–232, 1998) and may cause a variety of ocular symptoms that mimic dry eye (Br J Ophthalmol 88:388–392, 2004). CCh disturbs the preocular tear film by blocking the tear drainage, disrupting the tear meniscus,...

Pterygium is characterized by encroachment of an abnormal fibrovascular tissue from the bulbar conjunctiva onto the cornea (Arch Ophthalmol 115:1235–1240, 1997). Upon reaching the corneal surface, this fibrovascular tissue exerts cicatricial traction that flattens the caruncle and obliterates the semilunar fold (Arch Ophthalmol 130:39–49, 2012). Th...

Salzmann’s nodular degeneration is a progressive degenerative disease of the cornea that is characterized by the multiple nodular bluish-gray opacities with various number and size (Z Augenheilkd 57:92–99, 1925). The indications for surgery include reduced vision due to encroachment on the visual axis, irregular astigmatism, chronic irritation, and...

Purpose: To evaluate morselized amniotic membrane and umbilical cord (AMUC) eye drops in promoting corneal re-epithelialization. Methods: Following a 2-mm diameter central epithelial wound in one eye of 48 normal C57BL/6 mouse corneas, 10 μL of saline with (n = 24) or without (n = 24) AMUC was applied three times a day for 6 days. The corneal ep...

Proliferative vitreoretinopathy (PVR) is mediated by proliferation and epithelial mesenchymal transition (EMT) of retinal pigment epithelium (RPE). Because heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) purified from human amniotic membrane exerts anti-inflammatory and anti-scarring actions, we hypothesized that HC-HA/PTX3 could inhibit these...

Background: Prenatal spina bifida (SB) repair with a regenerative patch may improve neurological outcomes by decreasing inflammatory scarring. Objective: This study aims to compare cryopreserved human umbilical cord (HUC) and biocellulose film (BCF) patches sutured over SB lesions for regeneration of native cells and inflammatory response. Stud...

Chronic graft-versus-host disease (cGVHD) is a major complication of hematopoietic stem cell transplantation. Dry eye disease is the prominent ocular sequel of cGVHD and is caused by excessive inflammation and fibrosis in the lacrimal glands. Heavy chain-Hyaluronan/Pentraxin 3 (HC-HA/PTX3) is a complex purified from human amniotic membrane (AM) and...

Human corneal endothelial cells (HCECs) have limited proliferative capacity due to “contact-inhibition” at G1 phase. Such contact-inhibition can be delayed from Day 21 to Day 42 by switching EGF-containing SHEM to LIF/bFGF-containing MESCM through transient activation of LIF-JAK1-STAT3 signaling that delays eventual nuclear translocation of p16INK4...

The ocular surface is covered by an epithelium encompassing an area including the cornea, the limbus and the conjunctiva bordered by the upper and lower lids. The healthy state of the ocular surface epithelium depends on a stable and protective preocular tear film when the eye is open. A stable preocular tear film is governed by sound ocular surfac...

Osteoarthritis (OA) is a progressive degenerative joint disease and to date, no disease modifying osteoarthritis drug exist. Amniotic membrane and umbilical cord products have been used clinically in several diseases due to their anti-inflammatory and anti-scarring properties. In the present study, we sought to evaluate whether a particulate amniot...

Objectives The objective of our study was to test the hypothesis that in utero repair of surgically created spina bifida in a sheep model using cryopreserved human umbilical cord (HUC) patch improves neurological outcome. Methods Spina bifida with myelotomy was surgically created in timed pregnant ewes at gestational day (GD) 75. The fetuses were...

Background: There is an urgent need is for a regenerative patch for in utero repair of spina bifida in situations in which primary closure is difficult. Cases: We present two cases of large myeloschisis defects that underwent in utero spina bifida repair at midgestation with closure of the skin defect by using a cryopreserved human umbilical cor...

Purpose: To evaluate the clinical efficacy of morselized amniotic membrane and umbilical cord tissue (MAU) in treating refractory corneal epithelial defect in ocular cicatricial diseases. Methods: Retrospective review of four patients with ocular cicatricial diseases treated with topical MAU for corneal epithelial defects refractory to conventio...

Purpose: Human limbal palisade of Vogt is an ideal model for studying and practicing regenerative medicine due to their accessibility. Nonresolving inflammation is a common manifestation of limbal stem cell deficiency, which is the major cause of corneal blindness, and presents as a threat to the success of transplanted limbal epithelial stem cell...

Purpose: To evaluate the effect of sutureless cryopreserved amniotic membrane (Prokera) on corneal wound healing after photorefractive keratectomy (PRK). Setting: Center for Refractive Surgery, Walter Reed Army Medical Center, Washington, DC, USA. Design: Prospective nonrandomized control trial. Methods: Patients had PRK for myopia with or w...

Purpose: To determine whether conjunctivochalasis (CCh) obliterates the fornix tear reservoir and to discern whether there is concomitant aqueous tear deficiency (ATD) dry eye. Methods: Retrospective review of 18 eyes of 12 patients with CCh and ATD (CCh + ATD) and 18 eyes of 13 patients with CCh without ATD (CCh - ATD). Changes were compared be...

Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a...

Human limbal palisades of Vogt are the ideal site for studying and practicing regenerative medicine due to their accessibility. Nonresolving inflammation in limbal stroma is common manifestation of limbal stem cell (SC) deficiency and presents as a threat to the success of transplanted limbal epithelial SCs. This pathologic process can be overcome...

The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized i...

Objective: To identify a patch system to repair surgically created spina bifida in a sheep model for its efficacy in healing the skin defect, protecting the underlying spinal cord and reducing the Chiari II malformation. Methods: Spina bifida was created surgically in 16 fetuses from eight timed-pregnant sheep at gestational age of 75 days. Two...

Purpose: To evaluate the clinical efficacy of self-retained cryopreserved amniotic membrane in treating dry eye disease. Methods: Retrospective review of 10 patients treated with self-retained cryopreserved amniotic membrane (PROKERA® Slim [PKS], Bio-Tissue, Miami, FL) for moderate-to-severe dry eye refractory to conventional maximal medical tre...

To explore how limbal niche cells (LNCs) may control quiescence, self-renewal and corneal epithelial lineage commitment/differentiation of limbal epithelial progenitor/stem cells (LEPCs), we have established an in vitro sphere assay by reunion between the two cell types in 3D Matrigel. The resultant sphere exhibits inhibition of corneal epithelial...

To summarize recent advances on ocular Demodex infestation. Demodex infestation is a potential cause of ocular surface inflammation. The pathogenesis of Demodex in eliciting ocular surface inflammation has been further clarified. Cliradex is currently the treatment of choice, it comprises the most active ingredient of tea tree oil, that is terpinen...

Human corneal endothelial cells (HCEC) play a pivotal role in maintaining corneal transparency. Unlike in other species, HCEC are notorious for their limited proliferative capacity in vivo after diseases, injury, aging, and surgery. Persistent HCEC dysfunction leads to sight-threatening bullous keratopathy with either an insufficient cell density o...

To report the surgical outcome of "Sealing the Gap" in treating symblepharon caused by various etiologies other than recurrent pterygium. Retrospective, interventional case series. Sixteen eyes of 14 patients with pathogenic symblepharon were consecutively operated by conjunctival recession, sealing the gap between recessed conjunctiva and Tenon's...

Described herein are methods and compositions for stimulating proliferation of cells that express adherent junctions and cease proliferation, for example, human corneal endothelial cells, by downregulation of certain cell-cell junctions. In one embodiment, downregulation is achieved using RNA interference, and contacting the cells with mitogenic gr...

Cryopreserved amniotic membrane (AM) is known to have potent anti-inflammatory mediators, a myriad of growth factors and an active matrix that are important to promote regenerative healing of the ocular surface. Hence, amniotic membrane transplantation (AMT) has successfully been used to treat a number of non-healing corneal epithelial defects caus...

Human corneal endothelial cells (HCECs) responsible for corneal transparency have limited proliferative capacity in vivo because of "contact-inhibition". This feature has hampered the ability to engineer HCECs for transplantation. Previously we have reported an in vitro model of HCECs in which contact inhibition was re-established at Day 21, even t...

The present invention relates to a method for treating a disorder chosen from ocular Demodex, Demodex-induced blepharitis, rosacea, acne, and meibomian gland dysfunction in a patient in need thereof, comprising administering to the patient a compositions comprising a therapeutically effective amount of a substance chosen from at least one of an iso...

Compositions containing about 0.6% to about 20% of tea tree oil are described. Some compositions are in the form of solutions, suspensions, spray, lotions, gels, pastes, medicated sticks, balms, cleansers (including shampoos and soaps), creams, or ointments. Also described are compositions and methods for use in treating ocular Demodex infestations...

Objective: To evaluate how the different processing methods cryopreservation and dehydration affect the structural integrity and biological composition of key signalling molecules within amniotic membrane and umbilical cord tissues. Method: We directly compared cryopreserved amniotic membrane (AM) and umbilical cord (UC) tissues with dehydrated...

Currently there are limited treatment options for corneal blindness caused by dysfunctional corneal endothelial cells. The primary treatment involves transplantation of healthy donor human corneal endothelial cells, but a global shortage of donor corneas necessitates other options. Conventional tissue approaches for corneal endothelial cells are ba...

Purpose: Adipose-derived stem cells (ASCs) have gained importance due to their myriad potential clinical applications. We hypothesize that progenitor cells also exist besides those conventionally isolated from the stromal vascular fraction (SVF). Method: Central and medial orbital adipose tissues obtained from patients during eyelid surgery were...