Medicine › Radiology, Nuclear Medicine and Imaging

Corneal Surgery and Treatments

Works Count: 39119

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Description

This cluster of papers focuses on advances in corneal tissue engineering and regeneration, with a particular emphasis on the use of limbal stem cells, amniotic membrane, and stem cell therapy for corneal reconstruction. The research covers topics such as corneal neovascularization, epithelial cell transplantation, wound healing, and the use of Boston Keratoprosthesis. These studies contribute to the development of innovative approaches for treating ocular surface disorders and promoting corneal regeneration.

Keywords

Corneal Regeneration; Tissue Engineering; Limbal Stem Cells; Amniotic Membrane; Corneal Neovascularization; Stem Cell Therapy; Epithelial Cell Transplantation; Wound Healing; Keratocyte Phenotype; Boston Keratoprosthesis

The X, Y, Z hypothesis of corneal epithelial maintenance.

1983-10-01

R A Thoft , J Friend

Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor.

1991-07-01

Scott W. Cousins , Mead M. McCabe , David Danielpour +1 more

The anterior chamber of the eye is an immunologically privileged site. Over the past 15 years, numerous laboratories documented that the privileged status of this unique site is mediated by … The anterior chamber of the eye is an immunologically privileged site. Over the past 15 years, numerous laboratories documented that the privileged status of this unique site is mediated by multifactorial immunoregulatory processes. Among the participating factors is the aqueous humor that circulates in the anterior chamber and is in contact with most of the tissues in the anterior segment of the eye. Recently, it was found that normal aqueous humor is a powerful inhibitor of antigen-driven T lymphocyte activation, but it spares other important functional properties of T cells. The spectrum of immune inhibitory properties resembles some of the activities of transforming growth factor-beta (TGF-beta), a polypeptide cytokine. Because of this similarity, the authors tried to determine if TGF-beta is present in aqueous humor and whether this cytokine could account for the lymphocyte inhibitory activity of this biologic fluid. They found TGF-beta in aqueous humor by dot-blot analysis. Using the CCL-64 mink lung epithelial cell bioassay for this compound, TGF-beta bioactivity was shown in aqueous humor from several different species, including human. In rabbit and human aqueous humor, most of the biologic activity was due to TGF-beta 2 (80-90%). Dose-response curves generated by using purified porcine TGF-beta showed that aqueous humor contained sufficient concentrations of TGF-beta to account for the observed inhibition in several assays for T cell activation and proliferation. Partial purification of the lymphocyte inhibitor in rabbit aqueous humor by size exclusion in high-performance liquid chromatography demonstrated that several lymphocyte inhibitory fractions contained TGF-beta bioactivity. Finally, neutralizing antisera to TGF-beta 2 were able to reverse most of the lymphocyte inhibitory activity of aqueous humor. It was concluded that TGF-beta was present in high concentration in normal aqueous humor and that this cytokine contributed to the immunosuppressive properties of aqueous humor.

An SV40-immortalized human corneal epithelial cell line and its characterization.

1995-03-01

Kaoru Araki‐Sasaki , Yuichi Ohashi , T Sasabe +4 more

The authors attempted to immortalize human corneal epithelial cells; it is difficult to propagate primary human corneal epithelial cells because of scarcity of available tissue. However, cell immortalization by virus … The authors attempted to immortalize human corneal epithelial cells; it is difficult to propagate primary human corneal epithelial cells because of scarcity of available tissue. However, cell immortalization by virus is always accompanied by shedding of free virus. The current study was performed to establish a cell line that produces no free viral particle.Primary cultured human corneal epithelial cells were infected with a recombinant sv40-adenovirus vector and were cloned three times to obtain a continuously growing cell line. Morphologic, cytologic, and biochemical characteristics of this cell line were analyzed.This cell line continued to grow for more than 400 generations, exhibiting a cobblestone-like appearance similar to normal corneal epithelial cells in culture. Transmission electron microscopy showed the evidence for the characteristic features of epithelial cells, including desmosome formation and development of microvilli. It expressed cornea-specific, 64-kD cytokeratin in addition to five major insoluble proteins. By enzymatic analysis using NADP as a coenzyme and a gas chromatograph mass spectrometer, this cell line was found to possess 8.71 IU/mg protein of aldehydedehydrogenase activity. When this cell line was grown at air-liquid interface on collagen type I gel, it differentiated in a multilayered fashion.The authors have established an SV40-immortalized human corneal epithelial cell line with properties similar to normal corneal epithelial cells.

Cultivated corneal epithelial stem cell transplantation in ocular surface disorders

2001-09-01

Noriko Koizumi , Tsutomu Inatomi , Tomo Suzuki +2 more

Topographical control of cell behaviour: II. multiple grooved substrata

1990-04-01

P. Clark , Patricia Connolly , A. S. G. Curtis +2 more

ABSTRACT Electronics miniaturisation techniques have been used to fabricate substrata to study contact guidance of cells. Topographical guidance of three cell types (BHK, MDCK and chick embryo cerebral neurones) was … ABSTRACT Electronics miniaturisation techniques have been used to fabricate substrata to study contact guidance of cells. Topographical guidance of three cell types (BHK, MDCK and chick embryo cerebral neurones) was examined on grooved substrata of varying dimensions (4-24 μm repeat, 0.2-1.9 μm depth). Alignment to within 10° of groove direction was used as our criterion for guidance. It was found that repeat spacing had a small effect (alignment is inversely proportional to spacing) but that groove depth proved to be much more important in determining cell alignment, which increased with depth. Measurements of cell alignment and examination by scanning electron microscopy showed that BHK cells and MDCK cells interacted differently with grooved substrata, and also that the response of MDCK cells depended on whether or not the cells were isolated or part of an epithelial cell island. Guidance by a multiple topographical cue is greater than could be predicted from cells’ reactions to a single cue (Clark et al. Development 99: 439-448, 1987). Substratum topography is considered to be an important cue in many developmental processes. Cellular properties such as cytoskeletal organisation, cell adhesion and the interaction with other cells are discussed as being factors determining a cells susceptibility to topography.

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Tumor Growth and Neovascularization: An Experimental Model Using the Rabbit Cornea 2

1974-02-01

Michael A. Gimbrone , Ramzi S. Cotran , Stephen B. Leapman +1 more

By intracorneal implantation of tumors in the eyes of rabbits, the early neovascular response to solid tumor growth could be directly observed. Fragments of homologous tumors—Brown-Pearce epithelioma and V2 carcinoma—were … By intracorneal implantation of tumors in the eyes of rabbits, the early neovascular response to solid tumor growth could be directly observed. Fragments of homologous tumors—Brown-Pearce epithelioma and V2 carcinoma—were implanted into the avascular corneal stroma of rabbits at various distances from the limbus. Tumor growth and neovascular response of llmbal vessels were studied by: 1) Slit Lamp Stereomicroscopy, 2) histologic examination, 3) filling of vasculature with colloidal carbon, and 4) autoradiography after exposure to 3Hthymidine. Centrally placed tumors spread as thin plates until they reached within 2.5 ± 0.5 mm of the limbus, when new vessels began to grow from the limbal plexus toward the tumor edge. When tumors became vascularized, they grew rapidly into exophytic masses. Peripherally placed tumors evoked early neovascularization. The prevascular growth of incompatible rabbit homograft and mouse xenograft tumors suggested that the cornea, before its vascularization, was an immunologically privileged site for tumor growth. Intracorneal polyacrylamide gel implants containing tumor extracts elicited a specific pattern of corneal vascularization not observed with nonmalignant cell extracts. These experiments provide a new model for study of tumor growth and neovascularization in a site where there is anatomic separation of tumor cell stimulus from host vascular response; the technique of corneal gel implantation may be useful in the characterization of mediators of neovascularization.

Epithelial Injury Induces Keratocyte Apoptosis: Hypothesized Role for the Interleukin-1 System in the Modulation of Corneal Tissue Organization and Wound Healing

1996-04-01

Steven E. Wilson , Yu-Guang He , Jian Weng +4 more

Cytologlogic Evidence of Corneal Diseases with Limbal Stem Cell Deficiency

1995-10-01

Vilavun Puangsricharern , Scheffer C.G. Tseng

Purpose: To determine which human corneal diseases show similar abnormal corneal surfaces, characterized by conjunctival epithelial ingrowth (conjunctivalization), vascularization, and chronic keratitis (i.e., a constellation of signs termed limbal stem … Purpose: To determine which human corneal diseases show similar abnormal corneal surfaces, characterized by conjunctival epithelial ingrowth (conjunctivalization), vascularization, and chronic keratitis (i.e., a constellation of signs termed limbal stem cell dysfunction [deficiency], which have been noted in experimental rabbit models). Methods: A total of 134 impression cytology specimens of the perilimbal region collected from 1984 to 1994 were reviewed. Limbal deficiency was diagnosed if conjunctival goblet cells were found on the corneal surface. Results: Ninety-four patients were found to have limbal deficiency. Category 1 comprised 53 patients with a clear history showing limbal stem cell destruction by chemical/thermal burns, Stevens-Johnson syndrome, multiple surgeries and cryotherapies, contact lens wear, and severe microbial keratitis. Patients in category 2 (n = 41), did not have such a history, but gradual loss of stem cell functions overtime was disclosed and included diverse causes such as aniridia, multiple endocrine deficiencies, neurotrophic keratopathy, peripheral inflammatory keratopathy or limbitis, and idiopathy. The 40 remaining patients with suspicious findings did not have limbal deficiency. Conclusions: Impression cytology can be used to diagnose and monitor corneal diseases with limbal deficiency, which manifest distinct clinical problems and are generally poor candidates for penetrating keratoplasty. The identification of category 1 diseases allows one to consider limbal (stem cell) transplantation for surface reconstruction. The presence of category 2 diseases indicates that limbal stem cell functions can be modulated by developmental, hormonal, neuronal, vascular, and inflammatory factors in the limbal stroma. Purpose: To determine which human corneal diseases show similar abnormal corneal surfaces, characterized by conjunctival epithelial ingrowth (conjunctivalization), vascularization, and chronic keratitis (i.e., a constellation of signs termed limbal stem cell dysfunction [deficiency], which have been noted in experimental rabbit models). Methods: A total of 134 impression cytology specimens of the perilimbal region collected from 1984 to 1994 were reviewed. Limbal deficiency was diagnosed if conjunctival goblet cells were found on the corneal surface. Results: Ninety-four patients were found to have limbal deficiency. Category 1 comprised 53 patients with a clear history showing limbal stem cell destruction by chemical/thermal burns, Stevens-Johnson syndrome, multiple surgeries and cryotherapies, contact lens wear, and severe microbial keratitis. Patients in category 2 (n = 41), did not have such a history, but gradual loss of stem cell functions overtime was disclosed and included diverse causes such as aniridia, multiple endocrine deficiencies, neurotrophic keratopathy, peripheral inflammatory keratopathy or limbitis, and idiopathy. The 40 remaining patients with suspicious findings did not have limbal deficiency. Conclusions: Impression cytology can be used to diagnose and monitor corneal diseases with limbal deficiency, which manifest distinct clinical problems and are generally poor candidates for penetrating keratoplasty. The identification of category 1 diseases allows one to consider limbal (stem cell) transplantation for surface reconstruction. The presence of category 2 diseases indicates that limbal stem cell functions can be modulated by developmental, hormonal, neuronal, vascular, and inflammatory factors in the limbal stroma.

Limbal Stem Cells of the Corneal Epithelium

2000-03-01

Harminder S. Dua , Augusto Azuara‐Blanco

Ocular surface squamous neoplasia

1995-05-01

Graham Lee , Lawrence W. Hirst

AUTOLOGOUS FIBRIN-CULTURED LIMBAL STEM CELLS PERMANENTLY RESTORE THE CORNEAL SURFACE OF PATIENTS WITH TOTAL LIMBAL STEM CELL DEFICIENCY1

2001-11-01

Paolo Rama , С. Бонини , Alessandro Lambìase +4 more

Background. Ocular burns cause depletion of limbal stem cells, which leads to corneal opacification and visual loss. Autologous cultured epithelial cells can restore damaged corneas, but this technology is still … Background. Ocular burns cause depletion of limbal stem cells, which leads to corneal opacification and visual loss. Autologous cultured epithelial cells can restore damaged corneas, but this technology is still developing. We sought to establish a culture system that allows preservation of limbal stem cells and preparation of manageable epithelial sheets and to investigate whether such cultures can permanently restore total limbal stem cell deficiency. Methods. We selected a homogeneous group of patients whose limbal cell deficiency was evaluated by scoring the gravity of the clinical picture and the keratin expression pattern. Stem cells, obtained from the limbus of the contralateral eye, were cultivated onto a fibrin substrate and their preservation was evaluated by clonal analysis. Fibrin cultures were grafted onto damaged corneas. Results. Fibrin-cultured limbal stem cells were successful in 14 of 18 patients. Re-epithelialization occurred within the first week. Inflammation and vascularization regressed within the first 3–4 weeks. By the first month, the corneal surface was covered by a transparent, normal-looking epithelium. At 12–27 months follow-up, corneal surfaces were clinically and cytologically stable. Three patients had a penetrating keratoplasty approximately 1 year after restoration of their corneal surface. Their visual acuity improved from light perception or counting fingers to 0.8–1.0. Conclusions. Preservation of limbal stem cells in culture gives new perspectives on the treatment of ocular disorders characterized by complete limbal stem cell deficiency. The multicenter nature of this study and the handiness and ease of long-distance transportation of the fibrin-cultured epithelial sheets suggest that this technology can now be widely applied.

Comparison of Conjunctival Autografts, Amniotic Membrane Grafts, and Primary Closure for Pterygium Excision

1997-06-01

Pinnita Prabhasawat , Keith Barton , Gene Burkett +1 more

Objective: The purpose of the study is to determine whether amniotic membrane can be used as an alternative to conjunctival autograft after pterygium excision. Design: A prospective study of amniotic … Objective: The purpose of the study is to determine whether amniotic membrane can be used as an alternative to conjunctival autograft after pterygium excision. Design: A prospective study of amniotic membrane grafts (group A) and primary closure (group B) was compared retrospectively with conjunctival autografts (group C) in patients with pterygia. Participants: Group A included 46 eyes with primary pterygia and 8 eyes with recurrent pterygia, group B had 20 eyes with primary pterygia, and group C consisted of 78 eyes with primary and 44 eyes with recurrent pterygia. Intervention: For the above three different surgeries, the amount of tissue removed was estimated from histopathologic analysis, and the result was evaluated by clinical examination. Main Outcome Measures: Recurrence, survival analysis, and final appearance were compared. Results: In group A, the recurrence rate was 10.9%, 37.5%, and 14.8% for primary, recurrent, and all pterygia, respectively (mean follow-up, 11 months). These three rates were significantly higher than 2.6%, 9.1 %, and 4.9% noted in group C (mean follow-up, 23 months) (P < 0.001, 0.018, and 0.01, respectively). However, the latter recurrence rate was significantly lower than 45% (mean follow-up, 5.2 months) in group B for primary pterygia (P < 0.001). The onset of recurrence was delayed significantly in group C as compared with that of groups A and B. Conclusions: The relatively low recurrence rate for primary pterygia allows one to use amniotic membrane transplantation as an alternative first choice, especially for advanced cases with bilateral heads or those who might need glaucoma surgery later.

Chemical injuries of the eye: Current concepts in pathophysiology and therapy

1997-01-01

Michael D. Wagoner

Limbal Autograft Transplantation for Ocular Surface Disorders

1989-05-01

Kenneth R. Keivyon , Scheffer C.G. Tseng

Conjunctival Autograft Transplantation for Advanced and Recurrent Pterygium

1985-11-01

Kenneth R. Kenyon , Michael D. Wagoner , Michael E. Hettinger

Kerato-epithelin mutations in four 5q31-linked corneal dystrophies

1997-03-01

Francis L. Munier , Elena Korvatska , Assia Djemaï +4 more

Reconstruction of Damaged Corneas by Transplantation of Autologous Limbal Epithelial Cells

2000-07-13

Ray Jui-Fang Tsai , Lien-Min Li , Jan-Kan Chen

The Stevens–Johnson syndrome, ocular pemphigoid, and thermal or chemical burns can cause scarring and opacification of the cornea and loss of vision. Transplantation of epithelial cells from the limbus of … The Stevens–Johnson syndrome, ocular pemphigoid, and thermal or chemical burns can cause scarring and opacification of the cornea and loss of vision. Transplantation of epithelial cells from the limbus of the contralateral cornea can restore useful vision. However, this procedure requires a large limbal graft from the healthy eye and is not possible in patients who have bilateral lesions.

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Serious Complications of Topical Mitomycin-C after Pterygium Surgery

1992-11-01

Roy S. Rubinfeld , Roswell R. Pfister , Raymond Stein +5 more

Background: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. Methods: The authors report on a series of 10 patients who experienced … Background: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. Methods: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. Results: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). Conclusion: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed. Background: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. Methods: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. Results: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). Conclusion: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed.

Proliferative capacity of the corneal endothelium

2003-03-25

Nancy C. Joyce

Treatment of Severe Ocular-Surface Disorders with Corneal Epithelial Stem-Cell Transplantation

1999-06-03

Kazuo Tsubota , Yoshiyuki Satake , Minako Kaido +4 more

Conditions that destroy the limbal area of the peripheral cornea, such as the Stevens–Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium. … Conditions that destroy the limbal area of the peripheral cornea, such as the Stevens–Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium. The result is scarring and opacification of the normally clear cornea. Standard corneal transplantation cannot treat this form of functional blindness.

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Tumor invasion through the human amniotic membrane: Requirement for a proteinase cascade

1986-11-01

Paolo Mignatti , E. Robbins , Daniel B. Rifkin

Transplantation of Preserved Human Amniotic Membrane for Surface Reconstruction in Severely Damaged Rabbit Corneas

1995-09-01

Jae Chan Kim , Scheffer C.G. Tseng

After n-heptanol removal of the total corneal epithelium and a limbal lamellar keratectomy, 23 rabbit eyes developed features of limbal stem cell deficiency including conjunctival epithelial ingrowth, vascularization and chronic … After n-heptanol removal of the total corneal epithelium and a limbal lamellar keratectomy, 23 rabbit eyes developed features of limbal stem cell deficiency including conjunctival epithelial ingrowth, vascularization and chronic inflammation. One month later, 10 control eyes received a total keratectomy, and 13 experimental eyes received additional transplantation of glycerin-preserved human amniotic membrane. In 3 months of follow-up, all control corneas were revascularized to the center with granuloma and retained a conjunctival epithelial phenotype. In contrast, five corneas in the experimental group became clear with either minimal or no vascularization; the rest had either mid peripheral (n = 5) or total (n = 3) vascularization and cloudier stroma. The success of corneal surface reconstruction correlated with the return of a cornea-like epithelial phenotype and the preservation of amniotic membrane, whereas the failure maintained a conjunctival epithelial phenotype and the amniotic membrane was either partially degraded or covered by host fibrovascular stroma. These results suggest that measures taken to facilitate epithelialization without allowing host fibrovascular ingrowth onto the amniotic membrane might prove this procedure clinically useful for ocular surface reconstruction.

An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris

2009-10-20

Magali Saint‐Geniez , Tomoki Kurihara , Eiichi Sekiyama +2 more

Clinical and experimental observations indicate a role for VEGF secreted by the retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris (CC). VEGF in mice is produced as three … Clinical and experimental observations indicate a role for VEGF secreted by the retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris (CC). VEGF in mice is produced as three isoforms, VEGF120, VEGF164, and VEGF188, that differ in their ability to bind heparan sulfate proteoglycan. RPE normally produces the more soluble isoforms, VEGF120 and VEGF164, but virtually no VEGF188, reflecting the fact that molecules secreted by the RPE must diffuse across Bruch's membrane (BrM) to reach the choriocapillaris. To determine the role of RPE-derived soluble VEGF on the choriocapillaris survival, we used mice that produce only VEGF188. VEGF188/188 mice exhibited normal choriocapillaris development. However, beginning at 7 months of age, we observed a progressive degeneration characterized by choriocapillaris atrophy, RPE and BrM abnormalities, culminating in areas of RPE loss and dramatic choroidal remodeling. Increased photoreceptor apoptosis in aged VEGF188/188 mice led to a decline in visual acuity as detected by electroretinogram (ERG). These changes are reminiscent of geographic atrophy (GA) and point to a role for RPE-derived VEGF in the maintenance of the choriocapillaris.

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Staging of Conjunctival Squamous Metaplasia by Impression Cytology

1985-06-01

Scheffer C.G. Tseng

Growth factor mRNA and protein in preserved human amniotic membrane

2000-01-01

Noriko Koizumi , Tsutomu Inatomi , Chie Sotozono +3 more

To investigate the expression of growth factor mRNA and the level of growth factor protein in preserved human amniotic membrane (AM).RT-PCR was used to examine the expression of mRNA for … To investigate the expression of growth factor mRNA and the level of growth factor protein in preserved human amniotic membrane (AM).RT-PCR was used to examine the expression of mRNA for eight growth factors (EGF, TGF-alpha, KGF, HGF, bFGF, TGF-beta1, -beta2, -beta3) and two growth factor receptors (KGFR and HGFR) in human AM preserved at -80 degrees C for one month. In addition, ELISAs were used to measure the protein concentrations of seven growth factors (EGF, TGF-alpha, KGF, HGF, bFGF, TGF-beta1, -beta2) in preserved human corneas and in AM both with and without amniotic epithelium.RT-PCR revealed that human AM expresses mRNA for EGF, TGF-alpha, KGF, HGF, bFGF, TGF-beta1, -beta2, -beta3, KGFR and HGFR, while ELISAs showed that it contains EGF, TGF-alpha, KGF, HGF, bFGF, TGF-beta1, -beta2. AM without amniotic epithelium also contains all seven growth factors examined, however, in this tissue the protein levels of EGF, KGF, HGF and bFGF were found to be significantly lower than in native AM.Preserved human AM expresses mRNAs for a number of growth factors and contains several growth factor proteins that might benefit epithelialization after AM transplantation. High levels of EGF, KGF, HGF and bFGF in AM with amniotic epithelium as compared to AM without amniotic epithelium suggest an epithelial origin for these growth factors. We feel that EGF, KGF and HGF in particular might play important roles in ocular surface wound healing after AM transplantation.

Role of the Pericorneal Papillary Structure in Renewal of Corneal Epithelium

1971-02-01

Martin Davanger , A. Evensen

Amniotic Membrane Transplantation With or Without Limbal Allografts for Corneal Surface Reconstruction in Patients With Limbal Stem Cell Deficiency

1998-04-01

Scheffer C.G. Tseng

<h3>Objective</h3> To examine whether amniotic membrane transplantation (AMT), in preparing the perilimbal stroma, enhances the success of allograft limbal transplantation (ALT). <h3>Methods</h3> Thirty-one eyes of 26 consecutive patients had cytologically … <h3>Objective</h3> To examine whether amniotic membrane transplantation (AMT), in preparing the perilimbal stroma, enhances the success of allograft limbal transplantation (ALT). <h3>Methods</h3> Thirty-one eyes of 26 consecutive patients had cytologically proven limbal deficiency resulting from chemical burns (14 eyes); Stevens-Johnson syndrome, toxic epidermal necrolysis, or pseudopemphigoid (5 eyes); contact lens–induced keratopathy (3 eyes); aniridia (3 eyes); multiple surgical procedures (2 eyes); atopy (2 eyes); or an unknown cause (2 eyes). Based on the severity of limbal deficiency, group A (mild), comprising 10 eyes, received AMT alone; group B (moderate), comprising 7 eyes, received AMT and ALT; and group C (severe), comprising 14 eyes, received AMT, ALT, and penetrating keratoplasty. All patients except those in group A received continuous oral cyclosporine. <h3>Results</h3> Except for the 2 eyes with atopy, all amniotic membrane–covered surfaces showed rapid epithelialization (in 2 to 4 weeks) and reduced inflammation, vascularization, and scarring, and the surfaces became smooth and wettable. For the mean follow-up period of 15.4 months, 25 (83%) of 30 eyes showed visual improvement, consisting of 6 or more lines (13 eyes), 4 to 5 lines (6 eyes), or 1 to 3 lines (6 eyes). Visual improvement decreased with the severity of limbal deficiency from 8 (100%) of 8 eyes in group A to 5 (71%) of 7 eyes in group B and 11 (79%) of 14 eyes in group C. In group C, corneal graft rejection occurred in 9 (64%) of 14 eyes, and reversible early limbal allograft rejection was noted in 3 (14%) of 21 eyes of groups B and C. <h3>Conclusions</h3> For partial limbal deficiency with superficial involvement, AMT alone is sufficient and hence superior to ALT because there is no need to administer cyclosporine. For total limbal deficiency, additional ALT is needed, and AMT helps reconstruct the perilimbal stroma, with reduced inflammation and vascularization, which collectively may enhance the success of ALT.

Suppression of transforming growth factor-beta isoforms, TGF-? receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix

1999-06-01

Scheffer C.G. Tseng , De-Quan Li , Xiang Ma

Down-regulation of the transforming growth factor-beta (TGF-β) signaling system is a strategy for preventing scarring during wound healing. Human corneal and limbal fibroblasts were cultured on the stromal matrix side … Down-regulation of the transforming growth factor-beta (TGF-β) signaling system is a strategy for preventing scarring during wound healing. Human corneal and limbal fibroblasts were cultured on the stromal matrix side of preserved human amniotic membrane. The levels of TGF-β1, β2, and β3 and TGF-β type II receptor transcripts and TGF-β1 and β2 proteins were suppressed as early as 8 hr and more dramatically at 24 hr after contact with an amniotic membrane. This suppressive effect was accompanied by down-regulation of α-smooth muscle actin, EDA spliced form of fibronectin, and integrin α5. It persisted even when challenged by 10 ng/ml TGF-β1. In contrast with their counterparts grown on plastic or in collagen gel, such suppression in amniotic membrane cultures remained complete after 1 week of culturing. Cells cultured on amniotic membrane showed significantly reduced [3H]-thymidine incorporation compared to cells cultured on plastic and displayed no DNA fragmentation. These results reveal a novel mechanism by which the TGF-β signaling system, DNA synthesis, and subsequent myofibroblast differentiation can be suppressed by an amnionic membrane matrix. This action explains in part the antiscarring results of amniotic membrane transplantation used for ocular surface reconstruction, a surgical technique applicable to other subspecialties. It may also explain in part why fetal wound healing is scarless. J. Cell. Physiol. 179:325–335, 1999. © 1999 Wiley–Liss, Inc.

Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration

2010-06-23

Paolo Rama , Stanislav Matuška , Giorgio Paganoni +3 more

Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal … Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal stem-cell deficiency. We investigated the long-term clinical results of cell therapy in patients with burn-related corneal destruction associated with limbal stem-cell deficiency, a highly disabling ocular disease.We used autologous limbal stem cells cultivated on fibrin to treat 112 patients with corneal damage, most of whom had burn-dependent limbal stem-cell deficiency. Clinical results were assessed by means of Kaplan-Meier, Kruskal-Wallis, and univariate and multivariate logistic-regression analyses. We also assessed the clinical outcome according to the percentage of holoclone-forming stem cells, detected as cells that stain intensely (p63-bright cells) in the cultures.Permanent restoration of a transparent, renewing corneal epithelium was attained in 76.6% of eyes. The failures occurred within the first year. Restored eyes remained stable over time, with up to 10 years of follow-up (mean, 2.91+/-1.99; median, 1.93). In post hoc analyses, success--that is, the generation of normal epithelium on donor stroma--was associated with the percentage of p63-bright holoclone-forming stem cells in culture. Cultures in which p63-bright cells constituted more than 3% of the total number of clonogenic cells were associated with successful transplantation in 78% of patients. In contrast, cultures in which such cells made up 3% or less of the total number of cells were associated with successful transplantation in only 11% of patients. Graft failure was also associated with the type of initial ocular damage and postoperative complications.Cultures of limbal stem cells represent a source of cells for transplantation in the treatment of destruction of the human cornea due to burns.

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Effect of Pterygium Morphology on Pterygium Recurrence in a Controlled Trial Comparing Conjunctival Autografting With Bare Sclera Excision

1997-10-01

Donald Tan

<h3>Objectives:</h3> To compare success rates of conjunctival autografting and bare sclera excision for primary and recurrent pterygium in the tropics and to evaluate risk factors for pterygium recurrence. <h3>Methods:</h3> A … <h3>Objectives:</h3> To compare success rates of conjunctival autografting and bare sclera excision for primary and recurrent pterygium in the tropics and to evaluate risk factors for pterygium recurrence. <h3>Methods:</h3> A prospective, controlled clinical trial was performed in which 123 primary and 34 recurrent pterygia, matched for age and pterygium morphology, were randomized in 2 separate studies to receive either bare sclera excision or conjunctival autograft. The surgical procedures were performed by one surgeon and reviewed at 1, 3, 6, and 12 months after surgery by an independent observer. Pterygium morphology was clinically graded as atrophic, intermediate, or fleshy according to an assessment of pterygium translucency. Risk factors were assessed using likelihood ratio tests. Weibull curves were used to estimate recurrence rates allowing for the interval censoring. <h3>Results:</h3> In the group with primary pterygium (mean follow-up, 15.1 months), 38 (61%) of the 62 cases of bare sclera excision (heretofore referred to as the bare sclera group) had pterygium recur in contrast with 1 (2%) of the 61 cases of conjunctival autograft (heretofore referred to as the conjunctival autograph group) (<i>P</i><.001, likelihood ratio χ<sup>2</sup>test). Nontranslucency, or fleshiness of the pterygium, and not age was a significant risk factor for recurrence in the bare sclera group (<i>P</i><.001, likelihood ratio χ<sup>2</sup>test). In the group with recurrent pterygium (mean follow-up, 13.2 months), 14 (82%) of the 17 bare sclera group had pterygium recur, while no recurrences occurred among 17 cases in the conjunctival autograft group. Nontranslucency was again a highly significant factor for recurrence (<i>P</i><.001, likelihood ratio χ<sup>2</sup>test). <h3>Conclusions:</h3> Pterygium recurrence is related to pterygium morphology and fleshiness of the pterygium is a significant risk factor for recurrence if bare sclera excision is performed. Conjunctival autografting for primary and recurrent pterygium is effective in reducing pterygium recurrence compared with bare sclera excision.

Identification of Antiangiogenic and Antiinflammatory Proteins in Human Amniotic Membrane

2000-05-01

Yanxia Hao , David Hui‐Kang , David G. Hwang +2 more

Purpose. To identify the potential antiangiogenic and antiinflammatory proteins expressed in human amniotic membrane tissue. Methods. Human amniotic epithelial and mesenchymal cells were isolated from human amniotic membranes by sequential … Purpose. To identify the potential antiangiogenic and antiinflammatory proteins expressed in human amniotic membrane tissue. Methods. Human amniotic epithelial and mesenchymal cells were isolated from human amniotic membranes by sequential trypsin and collagenase digestion. Total RNAs were harvested from freshly obtained human amniotic epithelial and mesenchymal cells. Antiangiogenic and antiinflammatory proteins were detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique and further confirmed by DNA sequencing of PCR-amplified transcripts. The distribution of tissue inhibitors of metalloproteinase (TIMPs) were studied further by immunohistochemistry performed on paraffin-embedded amniotic membrane tissue. Results. RT-PCR results showed that both human amniotic epithelial and mesenchymal cells express interleukin-1 receptor antagonist, all four TIMPs, collagen XVIII, and interleukin-10. Thrombospondin-1 was expressed in all of the epithelial cell specimens and in one out of five mesenchymal cell specimens. Furthermore, immunohistochemistry studies performed on freshly prepared amniotic membrane confirmed that all members of the TIMP family were present in epithelial and mesenchymal cells as well as in the compact layer of the amniotic stroma. In cryopreserved amniotic membranes, positive staining was seen in residual amniotic cells and stroma. Conclusions. Human amniotic membrane epithelial and mesenchymal cells express various antiangiogenic and antiinflammatory proteins. Some of those proteins also were found in amniotic membrane stroma. These findings may explain in part the antiangiogenic and antiinflammatory effects of amniotic membrane transplantation.

Amniotic Membrane Transplantation for Persistent Epithelial Defects With Ulceration

1997-03-01

Shwu‐Huey Lee , Scheffer C.G. Tseng

Purpose To determine whether preserved human amniotic membrane can be used as an alternative substrate for treating persistent corneal epithelial defects with sterile ulceration. Methods Amniotic membrane transplantation was performed … Purpose To determine whether preserved human amniotic membrane can be used as an alternative substrate for treating persistent corneal epithelial defects with sterile ulceration. Methods Amniotic membrane transplantation was performed in 11 eyes of 11 consecutive patients with corneal ulcers of different causes that had persisted for a mean ± SD of 17.5 ± 13.9 weeks. Results Ten patients healed in 3.9 ± 2.3 weeks (P < .01) without recurrence for 9.0 ±5.9 months. One patient failed to heal because of preexisting corneal perforation pursuant to severe rheumatoid arthritis. Conclusion Amniotic membrane transplantation may be considered an alternative method for treating persistent epithelial defects and sterile ulceration that are refractory to conventional treatment and before considering treatment by conjunctival flaps or tarsorrhaphy. To determine whether preserved human amniotic membrane can be used as an alternative substrate for treating persistent corneal epithelial defects with sterile ulceration. Amniotic membrane transplantation was performed in 11 eyes of 11 consecutive patients with corneal ulcers of different causes that had persisted for a mean ± SD of 17.5 ± 13.9 weeks. Ten patients healed in 3.9 ± 2.3 weeks (P < .01) without recurrence for 9.0 ±5.9 months. One patient failed to heal because of preexisting corneal perforation pursuant to severe rheumatoid arthritis. Amniotic membrane transplantation may be considered an alternative method for treating persistent epithelial defects and sterile ulceration that are refractory to conventional treatment and before considering treatment by conjunctival flaps or tarsorrhaphy.

Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface

2004-02-01

Kohji Nishida , Masayuki Yamato , Yasutaka Hayashida +7 more

Background. Limbal stem-cell deficiency by ocular trauma or diseases causes corneal opacification and visual loss. Recent attempts have been made to fabricate corneal epithelial graft constructs, but the technology is … Background. Limbal stem-cell deficiency by ocular trauma or diseases causes corneal opacification and visual loss. Recent attempts have been made to fabricate corneal epithelial graft constructs, but the technology is still evolving. We have developed a novel cell-sheet manipulation technology using temperature-responsive culture surfaces to generate functional, cultivated corneal epithelial cell sheet grafts. Methods. Human or rabbit limbal stem cells were cocultured with mitomycin C -treated 3T3 feeder layers on temperature-responsive culture dishes at 37°C. Cell sheets were harvested from the dishes after 2 weeks by reducing temperature to 20°C. Histologic analyses, immunoblotting, and colony-forming assay were performed to characterize the cell sheets. Autologous transplantation was undertaken to reconstruct the corneal surfaces of rabbits with experimentally induced limbal stem cell deficiencies. Results. Multilayered corneal epithelial sheets were harvested intact simply by reducing the temperature, without the use of proteases. Cell-cell junctions and extracellular matrix on the basal side of the sheet, critical to sheet integrity and function, remained intact. A viable population of corneal progenitor cells, close in number to that originally seeded, was found in the sheets. Harvested sheets were easily manipulated, transplantable without any carriers, and readily adhesive to corneal stroma so that suturing was not required. Corneal surface reconstruction in rabbits was highly successful. Conclusions. Cell sheet engineering technology allows us to create intact, transplantable corneal epithelial cell sheets that retain stem cells from limbal stem cells expanded ex vivo. Our research indicates highly promising clinical capabilities for our bioengineered corneal epithelial sheet.

Concept and application of limbal stem cells

1989-03-01

Scheffer C.G. Tseng

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Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells.

1986-07-01

Alexander Schermer , Sharon Galvin , Tung‐Tien Sun

In this paper we present keratin expression data that lend strong support to a model of corneal epithelial maturation in which the stem cells are located in the limbus, the … In this paper we present keratin expression data that lend strong support to a model of corneal epithelial maturation in which the stem cells are located in the limbus, the transitional zone between cornea and conjunctiva. Using a new monoclonal antibody, AE5, which is highly specific for a 64,000-mol-wt corneal keratin, designated RK3, we demonstrate that this keratin is localized in all cell layers of rabbit corneal epithelium, but only in the suprabasal layers of the limbal epithelium. Analysis of cultured corneal keratinocytes showed that they express sequentially three major keratin pairs. Early cultures consisting of a monolayer of "basal" cells express mainly the 50/58K keratins, exponentially growing cells synthesize additional 48/56K keratins, and postconfluent, heavily stratified cultures begin to express the 55/64K corneal keratins. Cell separation experiments showed that basal cells isolated from postconfluent cultures contain predominantly the 50/58K pair, whereas suprabasal cells contain additional 55/64K and 48/56K pairs. Basal cells of the older, postconfluent cultures, however, can become AE5 positive, indicating that suprabasal location is not a prerequisite for the expression of the 64K keratin. Taken together, these results suggest that the acidic 55K and basic 64K keratins represent markers for an advanced stage of corneal epithelial differentiation. The fact that epithelial basal cells of central cornea but not those of the limbus possess the 64K keratin therefore indicates that corneal basal cells are in a more differentiated state than limbal basal cells. These findings, coupled with the known centripetal migration of corneal epithelial cells, strongly suggest that corneal epithelial stem cells are located in the limbus, and that corneal basal cells correspond to "transient amplifying cells" in the scheme of "stem cells----transient amplifying cells----terminally differentiated cells."

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Corneal Reconstruction with Tissue-Engineered Cell Sheets Composed of Autologous Oral Mucosal Epithelium

2004-09-15

Kohji Nishida , Masayuki Yamato , Yasutaka Hayashida +7 more

Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous … Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface.We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surface, sheets of cultured autologous cells that had been harvested with a simple reduced-temperature treatment were transplanted directly to the denuded corneal surfaces (one eye of each patient) without sutures.Complete reepithelialization of the corneal surfaces occurred within one week in all four treated eyes. Corneal transparency was restored and postoperative visual acuity improved remarkably in all four eyes. During a mean follow-up period of 14 months, all corneal surfaces remained transparent. There were no complications.Sutureless transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells may be used to reconstruct corneal surfaces and can restore vision in patients with bilateral severe disorders of the ocular surface.

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Location and Clonal Analysis of Stem Cells and Their Differentiated Progeny in the Human Ocular Surface

1999-05-17

Graziella Pellegrini , Osvaldo Golisano , Patrizia Paterna +4 more

We have analyzed the proliferative and differentiation potential of human ocular keratinocytes. Holoclones, meroclones, and paraclones, previously identified in skin, constitute also the proliferative compartment of the ocular epithelium. Ocular … We have analyzed the proliferative and differentiation potential of human ocular keratinocytes. Holoclones, meroclones, and paraclones, previously identified in skin, constitute also the proliferative compartment of the ocular epithelium. Ocular holoclones have the expected properties of stem cells, while transient amplifying cells have variable proliferative potential. Corneal stem cells are segregated in the limbus, while conjunctival stem cells are uniformly distributed in bulbar and forniceal conjunctiva. Conjunctival keratinocytes and goblet cells derive from a common bipotent progenitor. Goblet cells were found in cultures of transient amplifying cells, suggesting that commitment for goblet cell differentiation can occur late in the life of a single conjunctival clone. We found that conjunctival keratinocytes with high proliferative capacity give rise to goblet cells at least twice in their life and, more importantly, at rather precise times of their life history, namely at 45–50 cell doublings and at ∼15 cell doublings before senescence. Thus, the decision of conjunctival keratinocytes to differentiate into goblet cells appears to be dependent upon an intrinsic “cell doubling clock.” These data open new perspectives in the surgical treatment of severe defects of the anterior ocular surface with autologous cultured conjunctival epithelium.

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Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: Implications on epithelial stem cells

1989-04-01

George Cotsarelis , Shih-Zen Cheng , Gang Dong +2 more

Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium

1997-04-01

Graziella Pellegrini , Carlo Enrico Traverso , Adriano T. Franzi +3 more

Growth factors: importance in wound healing and maintenance of transparency of the cornea

2000-01-01

Jirô Imanishi , Kenji Kamiyama , Ikuo Iguchi +3 more

Ocular immune privilege: therapeutic opportunities from an experiment of nature

2003-11-01

J. Wayne Streilein

Corneal avascularity is due to soluble VEGF receptor-1

2006-10-01

Balamurali K. Ambati , Miho Nozaki , Nirbhai Singh +7 more

p63 identifies keratinocyte stem cells

2001-03-13

Graziella Pellegrini , Elena Dellambra , Osvaldo Golisano +6 more

The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but … The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but no polypeptide confined to the stem cells has yet been identified. Here we show that the p63 transcription factor, a p53 homologue essential for regenerative proliferation in epithelial development, distinguishes human keratinocyte stem cells from their TA progeny. Within the cornea, nuclear p63 is expressed by the basal cells of the limbal epithelium, but not by TA cells covering the corneal surface. Human keratinocyte stem and TA cells when isolated in culture give rise to holoclones and paraclones, respectively. We show by clonal analysis that p63 is abundantly expressed by epidermal and limbal holoclones, but is undetectable in paraclones. TA keratinocytes, immediately after their withdrawal from the stem cell compartment (meroclones), have greatly reduced p63, even though they possess very appreciable proliferative capacity. Clonal evolution (i.e., generation of TA cells from precursor stem cells) is promoted by the sigma isoform of the 14-3-3 family of proteins. Keratinocytes whose 14-3-3final sigma has been down-regulated remain in the stem cell compartment and maintain p63 during serial cultivation. The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis.

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Properties of the amniotic membrane for potential use in tissue engineering

2008-04-29

Hassan Niknejad , Habiballah Peirovi , Masoumeh Jorjani +3 more

An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and … An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Most scaffold materials are naturally derived from mammalian tissues. The amniotic membrane (AM) is considered an important potential source for scaffolding material. The AM represents the innermost layer of the placenta and is composed of a single epithelial layer, a thick basement membrane and an avascular stroma. The special structure and biological viability of the AM allows it to be an ideal candidate for creating scaffolds used in TE. Epithelial cells derived from the AM have the advantages of stem cells, yet are a more suitable source of cells for TE than stem cells. The extracellular matrix components of the basement membrane of the AM create an almost native scaffold for cell seeding in TE. In addition, the AM has other biological properties important for TE, including anti-inflammatory, anti-microbial, anti-fibrosis, anti-scarring, as well as reasonable mechanical property and low immunogenicity. In this review, the various properties of the AM are discussed in light of their potential use for TE.

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Anatomy of cornea and ocular surface

2018-01-01

MittanamalliS Sridhar

Important functions of cornea in the eye include protecting the structures inside the eye, contributing to the refractive power of the eye, and focusing light rays on the retina with … Important functions of cornea in the eye include protecting the structures inside the eye, contributing to the refractive power of the eye, and focusing light rays on the retina with minimum scatter and optical degradation. Considerable advances have taken place in understanding the organization of collagen in the corneal stroma and its clinical significance. In this review, the structure and function of various components of cornea and ocular surface are presented.

Amniotic Membrane in Ophthalmology

2020-05-22

Prateeksha Sharma

The amniotic membrane is the inner most layer of the three fetal membranes lying deep to chorion.It is translucent and avascular in nature.It is derived from fetal ectoderm by cavitation … The amniotic membrane is the inner most layer of the three fetal membranes lying deep to chorion.It is translucent and avascular in nature.It is derived from fetal ectoderm by cavitation within the fetal knot.It is composed of three layers: epithelium, basement membrane and stromal [1].The structural integrity, transparency and elasticity makes the amniotic membrane most widely accepted tissue for ocular surface reconstruction.

Corneal transplantation

2012-05-01

Donald Tan , John Dart , Edward J. Holland +1 more

Corneal neovascularization

2001-08-01

Jin‐Hong Chang , Éric Gabison , Takuji Kato +1 more

Corneal neovascularization (NV) is a sight-threatening condition usually associated with inflammatory or infectious disorders of the ocular surface. It has been shown in the field of cancer angiogenesis research that … Corneal neovascularization (NV) is a sight-threatening condition usually associated with inflammatory or infectious disorders of the ocular surface. It has been shown in the field of cancer angiogenesis research that a balance exists between angiogenic factors (such as fibroblast growth factor and vascular endothelial growth factor) and anti-angiogenic molecules (such as angiostatin, endostatin, or pigment epithelium derived factor) in the cornea. Several inflammatory, infectious, degenerative, and traumatic disorders are associated with corneal NV, in which the balance is tilted towards angiogenesis. The pathogenesis of corneal NV may be influenced by matrix metalloproteinases and other proteolytic enzymes. New medical and surgical treatments, including angiostatic steroids, nonsteroidal inflammatory agents, argon laser photocoagulation, and photodynamic therapy have been effective in animal models to inhibit corneal NV and transiently restore corneal "angiogenic privilege."

The Corneal Wound Healing Response:

2001-09-01

Steven E. Wilson , Rahul R. Mohan , Rajiv R. Mohan +3 more

Progress in corneal wound healing

2015-07-18

Alexander V. Ljubimov , Mehrnoosh Saghizadeh

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Clinical Outcomes of Stem Cell Therapy in Dogs With Keratoconjunctivitis Sicca; A Systematic Review and Meta‐Analysis

2025-06-25

Mojtaba Taheri , Masoud Bitaraf , Meysam Behtari +1 more | Veterinary Ophthalmology

ABSTRACT Background Keratoconjunctivitis sicca (KCS) results from a deficiency in the pre‐corneal tear film, causing persistent ocular discomfort and a predisposition to ocular surface diseases. Current treatments, including topical lacrimostimulants … ABSTRACT Background Keratoconjunctivitis sicca (KCS) results from a deficiency in the pre‐corneal tear film, causing persistent ocular discomfort and a predisposition to ocular surface diseases. Current treatments, including topical lacrimostimulants and lacrimomimetics, primarily offer symptomatic relief without restoring lacrimal gland function. Mesenchymal stem cell (MSC) therapy, with its regenerative and immunomodulatory properties, has been investigated in preclinical and veterinary studies but remains critically underexplored for its clinical relevance in treating KCS. Methods A systematic review was conducted on April 24, 2024, using Medline, Embase, Web of Science, and CABI databases. Studies evaluating MSC therapy in dogs and cats with KCS were included. Data collected included demographic information, baseline and post‐treatment Schirmer tear test (STT) values, and ocular symptoms such as discharge, conjunctival hyperemia, and corneal changes. The risk of bias was assessed using validated tools, and the quality of evidence was graded using the Oxford Centre for Evidence‐Based Medicine (OCEBM). Statistical analyses were performed with STATA to compare STT values at baseline and after 1‐ and 6‐month follow‐ups. Results Six studies involving 151 eyes from 98 dogs were included. Studies demonstrated low to moderate risk of bias, and evidence quality was graded as level C. MSC therapy significantly increased tear production and improved ocular comfort, with mean STT increases of 0.68 mm/min at 1 month and 1.51 mm/min at 6 months. Conclusion MSC therapy offers statistically significant improvements in tear production in dogs with KCS and is considered a safe treatment option. However, the modest clinical significance highlights the need for further research to confirm its efficacy.

Ocular argyrosis

2025-06-25

Vincenzo Maurino , Nerea Zubieta-Gonzalo , Gabriele Gallo Afflitto | Eye

The Human Amniotic Membrane and its Applications in Regenerative Dentistry: An Overview

2025-06-25

Esra Güzeldemir , Damla Kan-Karabiyik , Dilek Helvacıoğlu-Yiğit | Current Oral Health Reports

Autologous Transplantation of the Entire Bulbar Ocular Surface

2025-06-25

Enrica Sarnicola , Caterina Sarnicola , Federica Machetta +2 more | New England Journal of Medicine

Collagen-Based Conjunctival Tissue Equivalent: In Vitro Evaluation of Biocompatibility and Biomechanical Properties

2025-06-24

D.A. Krivolapova , A.Y. Andreev , А.М. Суббот +4 more | Genes and Cells

Background. Conjunctival damage leads to the formation of fibrosis and scarring of fornices, which reduces quality of life of patients. Collagen, as a natural component of the conjunctival stroma, has … Background. Conjunctival damage leads to the formation of fibrosis and scarring of fornices, which reduces quality of life of patients. Collagen, as a natural component of the conjunctival stroma, has high biocompatibility and weak antigenicity, which makes it a promising material for clinical practice. Evaluation of the biocompatibility and biomechanical properties of collagen-containing materials contributes to the further development of surgical techniques.Aim. To assess in vitro cytotoxicity of a collagen membrane (CM) for conjunctival epithelial cells (CECs), evaluate their morphology and protein expression after seeding onto CM, characterize the biomechanical properties of CM compared to conjunctival tissue.Materials and methods. The study was conducted at the M.M. Krasnov Research Institute of Eye Diseases. Primary CEC's cultures were established using the explant method. Cell type was verified via CK7, MUC5 staining. CMs with collagen concentrations of 10 and 30 mg/ml were evaluated. Cytotoxicity was assessed by seeding CECs (50,000/cm²) onto 30 mg/ml CM, followed by: 1) metabolic activity analysis via MTS assay; 2) live/dead staining with Calcein-AM and Hoechst. Morphology was analyzed using phase-contrast imaging on 10 and 30 mg/ml CM and after immunocytochemical staining for CK7, MUC5. Biomechanical properties of CM and native conjunctiva were tested via static and dynamic indentation. Results. CEC migration into the inner layers of 10 mg/ml CM within one week, while 30 mg/ml CM supported confluent monolayer growth on its surface. MTS assay showed no significant difference in metabolic activity between control and CM groups. Live/dead staining demonstrated 95% viability in both control and CM groups. Immunocytochemical profiles of CECs remained unchanged, with preserved CK7 and MUC5 expression, consistent with controls. Young’s modulus of CM (0.0008739 ± 0.0004332 GPa) and conjunctiva (0.0009472 ± 0.001323 GPa) were comparable (p=0.0549). CM exhibited higher hardness (p0.0001) and lower viscosity (p0.0001) than native tissue. Conclusion. CECs maintained viability on CM. Migration into the matrix suggests CM provides a favorable microenvironment for epithelialization and post-implantation resorption. Preserved molecular markers indicate high biocompatibility. CM matches conjunctival elasticity, its greater hardness and lower viscosity highlight opportunities for biomechanical optimization to clinical needs.

Human Platelet Lysate Treatment for Exposure Keratopathy: An In Vivo Confocal Microscopy and Anterior Segment OCT Study

2025-06-24

Chia‐Ying Tsai , Wei‐Lun Huang , Shang‐Chih Yang +5 more | Investigative Ophthalmology & Visual Science

To investigate the effects of topical human platelet lysate (HPL) on exposure keratopathy (EK) in a rabbit model, with a focus on its anti-inflammatory and anti-dehydration properties on the cornea. … To investigate the effects of topical human platelet lysate (HPL) on exposure keratopathy (EK) in a rabbit model, with a focus on its anti-inflammatory and anti-dehydration properties on the cornea. Short-term exposure keratopathy was induced in New Zealand albino rabbits by keeping the eyelids open for four hours, followed by eyelid closure for another four hours, during which the treatment was applied. HPL, fetal bovine serum (FBS), or preservative-free artificial tears (PFAT) were administered every 15 minutes, and corticosteroid was applied every one hour during the treatment period. Corneal thickness changes and epithelial defects were assessed using anterior segment optical coherence tomography (AS-OCT) and fluorescein staining. In vivo confocal microscopy (IVCM) was used to evaluate inflammatory cell infiltration, whereas immunohistochemistry (IHC) was performed to confirm the presence of CD8+ T cells, neutrophils, and macrophages and the cell proliferation marker Ki67. After completing the treatment, no significant difference in fluorescein staining was observed among the four groups. However, AS-OCT revealed more effective recovery of corneal thinning in the HPL- and FBS-treated groups, including improvements in epithelial, stromal, and total corneal thickness. IVCM revealed significantly reduced infiltration of inflammatory cells in the HPL-, FBS-, and corticosteroid-treated groups compared to the PFAT-treated group across the central cornea, peripheral cornea, and conjunctiva. IHC for CD8+ T cells, neutrophils, and macrophages showed similar findings. HPL-treated groups showed more Ki-67-positive cells compared to the PFAT- and corticosteroid-treated groups. HPL treatment effectively reduced inflammation, promoted the recovery of corneal thickness, and induced cellular proliferation after dehydration, demonstrating its potential as a treatment for EK.

Polystyrene microplastics impair the function of human retinal microvascular endothelial cells and pericytes and increase vascular permeability in vitro

2025-06-24

Jang‐Hyuk Yun | Frontiers in Medicine

Introduction Polystyrene (PS) microplastics are among the most prevalent types of microplastics responsible for global pollution. Although numerous studies have investigated the effects of PS on various organs, such as … Introduction Polystyrene (PS) microplastics are among the most prevalent types of microplastics responsible for global pollution. Although numerous studies have investigated the effects of PS on various organs, such as the heart, lungs, liver, kidneys, nervous system, and intestines, its impact on the eyes, particularly the retina, remains largely unexplored. Methods To assess the effects of PS on retinal pathology, cultured retinal microvascular endothelial cells, pericytes, astrocytes, and microglial cells were exposed to 2 μm PS particles. Cell viability (MTT assay), apoptosis (Annexin V/PI flow cytometry), protein expression (Western blotting), and angiogenesis-related behaviors (tube formation, migration, and permeability assays) were evaluated. Results PS induced endothelial cell apoptosis by reducing the activity of AKT and ERK1/2, and induced pericyte apoptosis by reducing the activity of AKT. PS also impaired tube formation, migration, and proliferation by reducing AKT and ERK1/2 activity in retinal endothelial cells. In addition, PS induced pericyte apoptosis and increased endothelial permeability. Conclusion PS may worsen retinopathy by inducing endothelial cell and pericyte apoptosis and by increasing vascular leakage, although it does not promote angiogenesis.

Engineering a functionality-integrated artificial cornea stromal Substitute: Janus bio-adhesive implant with a collagen-based multi-scale biomimetic skeleton

2025-06-24

Lei Miao , Yue Ji , Shaohua Zhang +5 more | Bioactive Materials

Correction to: Importin 13 Serves as a Potential Marker for Corneal Epithelial Progenitor Cells.

2025-06-24

| PubMed

Different Expression of Vascularization and Inflammatory Regulators in Cells Derived from Oral Mucosa and Limbus

2025-06-24

Eleni Voukali , João Victor Cabral , Natalia Smorodinova +4 more | Bioengineering

Bilateral limbal stem cell deficiency (LSCD) can be effectively treated with cultivated oral mucosa epithelial cell transplantation (COMET). However, COMET is associated with greater superficial neovascularization than limbal stem cell … Bilateral limbal stem cell deficiency (LSCD) can be effectively treated with cultivated oral mucosa epithelial cell transplantation (COMET). However, COMET is associated with greater superficial neovascularization than limbal stem cell (LESC) transplantation, the gold standard for unilateral LSCD. To investigate the intrinsic molecular features of cells intended for grafting, we assessed the in vitro expression of genes involved in vascularization and inflammation using real-time quantitative PCR and multifactorial linear models. Oral mucosal epithelial cells (OMECs) and limbal epithelial cells (LECs) were cultured in either conventional (COM) or xenobiotic-free (XF) media on fibrin substrates. Gene expression profiling revealed distinct transcriptional signatures. The pro-angiogenic genes AGR2, ANGPTL2, CRYAB, EREG, JAM3, and S100A4 were significantly higher in LECs (adjusted p < 0.01), whereas FGF2 was higher in OMECs (adjusted p < 0.001). The anti-angiogenic genes TIMP3 and SERPINF1 were higher in LECs (adjusted p < 0.01), while COL18A1 was higher in OMECs (adjusted p < 0.01). OMECs also showed significantly greater expression of the immunoregulatory genes IL1B, IL6, TNF, CXCL10, and IL1RN (adjusted p < 0.01). Cultivation induced phenotypic changes in OMECs, with COM and XF media exerting comparable effects. These results highlight the contribution of inflammatory mediators to neovascularization following COMET.

3D bioprinted GelMA/collagen hydrogel for corneal stroma regeneration

2025-06-24

Yingni Xu , Wenfang Liu , Qi Zhao +7 more | Biofabrication

Abstract Blindness caused by corneal stroma disease affects millions worldwide, the regeneration of corneal stroma has always been a challenge due to its sophisticated curvature structure and keratocyte-fibroblast transformation. In … Abstract Blindness caused by corneal stroma disease affects millions worldwide, the regeneration of corneal stroma has always been a challenge due to its sophisticated curvature structure and keratocyte-fibroblast transformation. In this study, we developed and optimized a series of gelatin methacrylate (GelMA)/collagen-based bioinks to fabricate convex corneal implants via 3D printing techniques. A novel method was proposed to enhance collagen solubility in neutral solutions by combining 2,3-epoxypropyltrimethylammonium chloride (EPTAC) with high-molecular-weight type I collagen, with simulations suggesting that the mechanism primarily involved electrostatic interactions. To evaluate whether keratocytes respond to a convex microenvironment and to verify the effectiveness of the proposed printing strategy for corneal stromal regeneration, particularly in mitigating corneal fibrosis, we fabricated topological structures of both flat and convex corneas. These structures were systematically analyzed for their influence on keratocyte-to-fibroblast transformation and keratocyte phenotype maintenance. Morphological observations, along with gene and protein expression analyses, demonstrated that the convex architecture provided an optimal microenvironment for preserving the keratocyte phenotype. Moreover, in vivo transplantation revealed the convex cornea effectively suppressed corneal fibrosis compared to the flat cornea. These findings suggest that convex cornea holds promise as a potential translational approach for treating corneal stroma regeneration.

Lifelong experience of modified osteo-odonto-keratoprosthesis implantation over 50 years

2025-06-23

Andrea Taloni , Paolo Colliardo , Maurizio Taloni +7 more | British Journal of Ophthalmology

The osteo-odonto-keratoprosthesis (OOKP) is a biological implant indicated for the treatment of eyes affected by corneal blindness, not amenable for keratoplasty. The purpose of the study is to report the … The osteo-odonto-keratoprosthesis (OOKP) is a biological implant indicated for the treatment of eyes affected by corneal blindness, not amenable for keratoplasty. The purpose of the study is to report the long-term outcomes of patients undergone Falcinelli's modified OOKP (MOOKP). In this retrospective study, anatomical and functional survival rates were evaluated using Kaplan-Meier analysis, according to eye coverage (buccal mucosa vs skin). Best-corrected visual acuity (BCVA) was recorded before and after surgery along with intraoperative and postoperative complications. 310 eyes of 269 patients affected by corneal blindness underwent MOOKP and were followed up for 15.9±12.0 years (up to 45 years). Anatomical survival rates for eyes covered by buccal mucosa were 85.1% at 20 years (number at risk (n)=81) and 82.3% at 45 years (n=10). Functional survival rates were 70.7% at 20 years (n=74) and 56.5% at 45 years (n=7). Anatomical and functional survival rates for eyes covered by skin were 58.9% (n=3) and 37.0% (n=3) at 20 years, respectively. Survival rates were significantly lower for eyes covered by skin (p<0.001). Postoperative BCVA at the last follow-up visit was significantly higher compared with baseline (0.88±1.08 LogMAR vs 2.49±0.38 LogMAR; p<0.001). The most threatening complications were glaucoma (n=70, 22.6%), endophthalmitis (n=24, 7.7%), retinal detachment (n=20, 6.4%), instability/tilting/expulsion of the optical cylinder and expulsion of the prosthesis (n=24, 7.7%). MOOKP showed excellent long-term anatomical and functional survival rates. Visual acuity significantly improved as soon as 3 months postoperatively and remained unchanged in about two-thirds of patients throughout the entire follow-up.

Uptake Inhibition to Improve Bioavailability of Nanoparticle-Mediated Growth Factor Delivery to the Corneal Epithelium

2025-06-22

Levi N. Kanu , Amit Chatterjee , Mohamed Mahmoud +7 more | ACS Pharmacology & Translational Science

Application and Evaluation of Full-thickness Keratoplasty for the Management of Irreparable Corneal Affections in Dogs

2025-06-19

Rohit Sharma , Shashi Kant Mahajan , N. Umeshwori Devi +1 more | Indian Journal of Animal Research

Background: Corneal transplant or full-thickness keratoplasty (FTKP) is considered as last line of treatment for severely damaged or opaque corneas where other treatment protocol could not be effective. There is … Background: Corneal transplant or full-thickness keratoplasty (FTKP) is considered as last line of treatment for severely damaged or opaque corneas where other treatment protocol could not be effective. There is lack of previous literature based on Indian context for corneal transplant in dogs hence present study was planned, cases of irreparable corneas were selected, operated and technique along with outcomes was evaluated. Methods: Total six clinical cases (n=6) of irreparable corneal diseases in different breeds of dogs were selected after complete necessary preoperative examinations including ophthalmological tests and ocular ultrasound. Healthy corneas were harvested along with sclera rim from dogs euthanized for untreatable conditions like trauma and systemic diseases. After collection, corneal tissue was stored in an air-tight container within ‘MK-medium.All the cases were operated successfully under general anaesthesia. Both fresh and frozen grafts were utilized for cornea transplant. Result: The mean value of donor graft size was 9.58±0.49 mm whereas recipient’s lesions size was 6.87±1.22 mm. The mean value of operative time was recorded as 73.33±14.25 minutes. Sutures used to affix donor graft with recipient’s bed ranged from 6 to 12 in numbers. After cornea transplant, only 2-eyes remained visual (due to surrounding transparent window) with 100% graft rejection in this study. Efficacy of this technique was determined by dividing the number of cases with visual outcomes to the total number of the eyes operated. Severe graft reaction, graft rejection, graft opacity, graft melanosis and development of post-surgical cataract were reported as postoperative complications.

Transparent Sodium Alginate Blended Polyvinyl Alcohol Hybrid Casting Film for Corneal Stromal Regeneration

2025-06-19

Amin Orash Mahmoud Salehi , Carlos Enrique Guerrero-Beltrán , Wendy Ortega-Lara | Materials Today Communications

Corneal Endothelium Regeneration with Decellularized Porcine Corneal Extracellular Matrix Scaffolds

2025-06-19

Cha Yeon Kim , C. Jeong , Hun Lee +1 more | Tissue Engineering and Regenerative Medicine

Effect of retinoic acid treatment on the retinoic acid signaling pathway in a human siRNA-based aniridia limbal epithelial cell model, in vitro

2025-06-18

Shao‐Lun Hsu , Tanja Stachon , Fabian N. Fries +7 more | PLoS ONE

Purpose In the present study, we evaluate gene and protein expression levels in an in vitro siRNA-mediated PAX6 knockdown limbal epithelial cell (LEC) model after RA treatment. This study aims … Purpose In the present study, we evaluate gene and protein expression levels in an in vitro siRNA-mediated PAX6 knockdown limbal epithelial cell (LEC) model after RA treatment. This study aims to investigate the direct effects of active RA products and their association with key regulators of the RA signaling pathway in siRNA PAX6 knockdown LECs, providing further insights into the potential role of RA signaling in AAK pathogenesis. Methods Primary human limbal epithelial cells (LECs) were subjected to siRNA-mediated PAX6 knockdown to mimic PAX6 deletion in congenital aniridia (n = 8). Following knockdown, 0 µM, 1 µM, and 5 µM all-trans retinoic acid (RA) treatments were applied to both the siRNA PAX6 control and knockdown groups. After 48 hours of incubation, the mRNA expression levels of paired box 6 (PAX6), alcohol dehydrogenase 7 (ADH7), retinol dehydrogenase 10 (RDH10), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), cytochrome P450 family 26 subfamily A member 1 (CYP26A1), retinol-binding protein 1 (RBP1), cellular retinoic acid-binding protein 2 (CRABP2), fatty acid-binding protein 5 (FABP5), retinoid X receptor alpha (RXRA), retinoid X receptor beta (RXRB), retinoic acid receptor alpha (RARA), retinoic acid receptor beta (RARB), peroxisome proliferator-activated receptor gamma (PPARG), and vascular endothelial growth factor A (VEGFA) were analyzed using qPCR. Protein expression levels were assessed using ELISA or Western blot, while cell proliferation rates were measured using the BrdU assay. Results PAX6 , ADH7 , ALDH1A1 , FABP5 mRNA levels and PAX6, ADH7, ALDH1A1, FABP5, PPARG2, RARB protein levels were significantly lower in the PAX6 knockdown group, than in controls (p ≤ 0.018). PPARG mRNA level was significantly higher in the PAX6 knockdown group than in controls (p = 0.012). ALDH1A1 mRNA expression was significantly downregulated using 5 µM RA treatment in the control group (p = 0.038). CYP26A1 mRNA expression was upregulated using 1 µM and 5 µM RA treatment in both the PAX6 control (p < 0.001; p < 0.001) and the PAX6 knockdown group (p = 0.001; p = 0.002). CRABP2 mRNA expression in the PAX6 knockdown group (p = 0.02) and CRABP2 protein expression in both groups were downregulated using 5 µM RA concentration (p = 0.003; p = 0.02). Protein expression of RXRA was downregulated to 5 µM RA treatment in the controls (p = 0.007). mRNA expression of RARA in the PAX6 knockdown groups (p = 0.023) and mRNA expression of RARB in both groups (p = 0.007, p < 0.001) were downregulated to 5 µM RA treatment. RARB protein expression was downregulated to 1 µM and 5 µM RA treatment (p = 0.02, p = 0.004) in the controls. VEGFA mRNA expression in PAX6 controls was upregulated using 5 µM RA (p = 0.041). Cell proliferation rate was downregulated in PAX6 knockdown groups compared to the controls and downregulated using 5 µM RA concentration only in the controls (p < 0.001, p = 0.025). Conclusions Our results reveal a reduced proliferation rate in PAX6 knockdown LECs, along with a less pronounced downregulation of proliferation in response to increased RA concentration. Additionally, the study highlights altered expression of key regulators in the RA signaling pathway, influenced by both PAX6 activity and RA treatment. These findings suggest a potential disruption in RA-mediated cellular regulation in PAX6-deficient LECs.

Surgical Pearls for Pterygium Surgery

2025-06-17

Randall Ulate | Canadian Eye Care Today

Pterygium, a common ocular surface disorder, manifests as a wing-shaped degenerative fibrovascular benign growth characterized by the fibrovascular proliferation of conjunctival tissue onto the cornea (Figure 1). This condition often … Pterygium, a common ocular surface disorder, manifests as a wing-shaped degenerative fibrovascular benign growth characterized by the fibrovascular proliferation of conjunctival tissue onto the cornea (Figure 1). This condition often results from prolonged exposure to ultraviolet light, dry eye conditions, or chronic irritation. On histopathology, there is classically elastotic degeneration of the conjunctival stroma with overgrowth of blood vessels and fibrous tissue, i.e., a fibro-proliferative reaction. While small and asymptomatic lesions may be managed conservatively, surgical excision becomes necessary when the lesion threatens vision, causes significant discomfort, or results in cosmetic concerns. A pterygium with documented growth that extends toward the visual axis should be removed before it reaches the central cornea. However, due to its high recurrence rate and variability in presentation, surgical management of pterygium requires attention to detail and a thorough understanding of optimal techniques.

Pseudomonas Keratitis in a Neurotrophic Cornea Ulcer Successfully Treated with Topical Antibiotics, Deep Anterior Lamellar Keratoplasty and Human Amniotic Membrane Transplantation

2025-06-17

Angelo Macrì , M. Tarallo , Laura Landi +1 more | Clinical Case Reports International

An 80-years old man came to our attention with severe infection keratitis in his left eye. The patient presented a history of recurrent herpetic keratopathy, leading to severe corneal hypoesthesia … An 80-years old man came to our attention with severe infection keratitis in his left eye. The patient presented a history of recurrent herpetic keratopathy, leading to severe corneal hypoesthesia and persistent neurotrophic ulceration in affected eye. Slit lamp examination revealed a large paracentral corneal ulcer with stromal melting and hypopyon. Corneal scraping was positive for P. aeruginosa sensitive to ceftazidime. Fortified topical antibiotics led to rapid resolution of the infection. However AS-OCT showed a severe stromal thinning. We performed a no stitch triplelayered human amniotic membrane transplantation (AMT) by using fibrin glue, followed by the application of a scleral contact lens, to reduce inflammation and to prepare the ocular surface for the subsequent deep anterior lamellar keratoplasty (DALK). A few days later, due to persistent corneal thinning, we proceeded with DALK, combined with AMT and with the application of a scleral contact lens. The sequential application of fortified antibiotics, trilaminar AMT, and subsequent DALK and AMT allowed a successful infection control, effective modulation of inflammation, and restoration of corneal structural integrity.

Effectiveness of Amniotic Membrane Transplantation in Corneal Ulcer Healing: A Systematic Review

2025-06-17

Anas Ahmed , Eyad M Albarrati , Abdulaziz Y Muyidi +7 more | Cureus

Management of infection and ocular complications in pediatric SJS/TEN-like acute graft-versus-host disease: a clinical case study and literature review

2025-06-16

Huimin Yan , Yunjun Mo , Yue Li +7 more | Frontiers in Immunology

Acute graft-versus-host disease (aGVHD) with skin manifestations reminiscent of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) is associated with poor outcomes. However, optimal management strategies to enhance quality of … Acute graft-versus-host disease (aGVHD) with skin manifestations reminiscent of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) is associated with poor outcomes. However, optimal management strategies to enhance quality of life in SJS/TEN-like aGVHD remain undefined. This study aims to investigate the management of complex infections and acute ocular injury in patients with SJS/TEN-like aGVHD following allogeneic hematopoietic stem cell transplantation. We conducted a comprehensive analysis of the treatment course for a patient with SJS/TEN-like aGVHD, complemented by a literature review on acute ocular complications and their management in aGVHD patients. A patient diagnosed with grade IV skin aGVHD received effective treatment for multidrug-resistant Stenotrophomonas maltophilia using minocycline, aztreonam, and ceftazidime-avibactam. Combination therapy with liposomal amphotericin B and voriconazole was efficacious against mixed fungal infections. Immunological assessments indicated reduced lymphocyte counts and increased myeloid-derived suppressor cells, with elevated CD4 + PD-1 + exhausted and memory cells, reflecting a complex interplay of immune hyperactivity and suppression. A literature review showed that although age, gender, and transplant circumstances were not associated with ocular symptoms, grade II+ cutaneous aGVHD emerged as a key risk factor for conjunctival involvement, characterized by exudation and pseudomembrane formation. Topical glucocorticoids, tacrolimus and cyclosporine eye drops were effective, necessitating regular pseudomembrane removal. Evaluating drug susceptibility and immune status is vital for formulating precise therapies. Early recognition and management of ocular symptoms in SJS/TEN-like aGVHD are essential to prevent irreversible damage.

Comparing Amniotic Membranes to Other Bioengineered Skin Substitutes in Wound Healing: A Propensity Score-Matched Analysis

2025-06-16

Micaela Tobin , Audrey K. Mustoe , Sasha Nickman +6 more | Journal of Clinical Medicine

Background/Objectives: The amniotic membrane, which is widely available and inexpensive, has received recent attention for its potential applications in wound healing. This is the first study to use a large … Background/Objectives: The amniotic membrane, which is widely available and inexpensive, has received recent attention for its potential applications in wound healing. This is the first study to use a large database to examine the efficacy of amniotic membrane grafting compared to other skin substitutes. Methods: The TriNetX electronic health database was queried in October 2024 for patients with burns or chronic skin ulcers. Patients were stratified by treatment with amniotic membrane grafts or another skin substitute. These patients were then 1:1 propensity score-matched based on age, demographics, and comorbidities. Group differences were assessed with risk ratios and p-values. Results: A total of 557 patients remained in each group after propensity score matching. Patients who were treated with amniotic membrane grafts had significantly decreased hypertrophic scarring (1.7% vs. 6.2%, p < 0.0001), local skin infections (17.4% vs. 29.9%, p < 0.0001), and acute postoperative pain (3.7% vs. 7.8%, p = 0.003). Additionally, subsequent split-thickness skin grafting was utilized significantly less after amniotic membrane grafts. When compared to skin substitutes for large wounds (>100 cm2), the advantages of amniotic membrane were even more pronounced. Conclusions: This multi-institutional study supports amniotic membranes as a viable alternative to conventional bioengineered skin substitutes. Further research should evaluate amniotic membranes in wound beds of different sizes to better characterize their use in preparation for or as an alternative to skin grafting itself.

TLR4 signal inhibition alleviates alkali-burn induced corneal neovascularization

2025-06-15

Chaohua Xia , Yan Deng , Yichen Lu +4 more | Experimental Eye Research

Outcome of amniotic membrane transplantation for corneal diseases in a tertiary referral center

2025-06-14

Michal Klimek , Irene Steiner , Gerald Schmidinger +2 more | Expert Review of Ophthalmology

Modern methods of eliminating conjunctival defects

2025-06-14

Ирина Филатова , С. А. Шеметов , Olesya V. Sokolova | Russian Ophthalmological Journal

The conjunctiva is a thin mucous, richly vascularized tissue lining the inner surface of the eyelids and the eyeball to the limbus and forming the space between the eyelids and … The conjunctiva is a thin mucous, richly vascularized tissue lining the inner surface of the eyelids and the eyeball to the limbus and forming the space between the eyelids and the eyeball — the conjunctival sac. Performing important physiological functions, the conjunctiva is a structure necessary for maintaining the normal anatomy and physiology of the eye. Conjunctival damage due to the impact of various factors can lead to the occurrence of significant functional disorders of the eye, which must be eliminated exclusively by surgery. Surgical treatment of conditions accompanied by conjunctival deficiency is currently considered one of the urgent and difficult tasks of ophthalmic surgery. There are many treatment tactics and modifications of operations to eliminate conjunctival defects, as well as local and total symblepharon, which are united by the need to use various replacement materials after moving the patient's own tissues. At the same time, the requirements for replacement tissues are quite high: they must be clinically compatible with the body's tissues, have the necessary elasticity, and be accessible for surgical transplantation. The ideal approach is to use one's own conjunctiva, but, unfortunately, it is not always feasible. The review presents experimental and clinical results of using modern surgical tactics: transplantation of autologous and allogeneic conjunctiva, oral mucosa, amniotic membrane, Alloplant biomaterial, autologous cultured epithelial cells of the oral mucosa.

Nailfold Video Capillaroscopy in Acute and Chronic Skin Graft Versus Host Disease

2025-06-13

Sehreen Mumtaz , Florentina Berianu , Puneet Bhullar +5 more | Mayo Clinic Proceedings Innovations Quality & Outcomes

Mitogen-Activated Protein Kinase Kinase Kinase 1 Overexpression Disrupts Development of the Ocular Surface Epithelium

2025-06-13

Maureen Mongan , Bo Xiao , Antonius Christianto +2 more | Cells

Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is a key signaling molecule essential for eyelid closure during embryogenesis. In mice, Map3k1 knockout leads to a fully penetrant eye-open at birth … Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is a key signaling molecule essential for eyelid closure during embryogenesis. In mice, Map3k1 knockout leads to a fully penetrant eye-open at birth (EOB) phenotype due to disrupted MAPK signaling, abnormal epithelial differentiation, and morphogenesis. To further explore the roles of MAP3K1 in ocular development, we generated a Cre-inducible gain-of-function transgenic mouse, designated as Map3k1TG, and crossed it with Lens epithelial (Le)-Cre mice to drive MAP3K1 overexpression in developing ocular surface epithelium (OSE). Map3k1TG;Le-Cre embryos exhibited ocular defects including premature eyelid closure, lens degeneration, and corneal edema. While corneal epithelial differentiation remained intact, the lens epithelium degenerated with lens formation compromised. Eyelid epithelium was markedly thickened, containing cells with aberrant keratin (K)14/K10 co-expression. Genetic rescue experiments revealed that Map3k1TG;Le-Cre restored eyelid closure in Map3k1 knockout mice, whereas MAP3K1 deficiency attenuated the epithelial thickening caused by transgene expression. Mechanistically, MAP3K1 overexpression enhanced c-Jun phosphorylation in vivo and activated JNK-c-Jun, WNT, TGFβ, and Notch signaling and promoted keratinocyte proliferation and migration in vitro. These findings highlight a dose-sensitive role for MAP3K1 in regulating epithelial proliferation, differentiation, and morphogenesis during eyelid development.

A Rare Case of Simultaneous Bilateral Corneal Perforations in Chronic Ocular Graft-Versus-Host Disease

2025-06-13

Anna Marmalidou , Leena Surapaneni , Sotiria Palioura | Ocular Immunology and Inflammation

To describe the clinical course and management of a patient with bilateral, simultaneous corneal perforations associated with chronic graft-versus-host disease (GVHD) and subsequent phacolytic glaucoma, highlighting the role of cyanoacrylate … To describe the clinical course and management of a patient with bilateral, simultaneous corneal perforations associated with chronic graft-versus-host disease (GVHD) and subsequent phacolytic glaucoma, highlighting the role of cyanoacrylate glue, amniotic membrane transplantation, and anterior segment optical coherence tomography (AS-OCT) in disease monitoring. Case report and literature review. A 58-year-old male with chronic ocular and skin GVHD presented with bilateral corneal perforations, confirmed via slit-lamp examination and AS-OCT. Initial visual acuity was light perception in both eyes. Immediate surgical management involved cyanoacrylate glue application and amniotic membrane transplantation, followed by medical therapy with systemic corticosteroids, topical antibiotics, autologous serum tears, and bandage contact lenses. Postoperatively, the patient's ocular surface stabilized, with corneal healing confirmed on AS-OCT. The patient later developed phacolytic glaucoma due to intumescent white cataracts, requiring endoillumination-assisted phacoemulsification. At 2.5 years, visual acuity had improved to 20/60 OD and 20/125 OS, with normal intraocular pressures and controlled ocular GVHD. While corneal perforation is a rare but sight-threatening complication of chronic ocular GVHD, simultaneous bilateral corneal perforations are exceptionally uncommon, with only one previously documented case in the literature. Cyanoacrylate glue and amniotic membrane transplantation provided effective stabilization, while AS-OCT facilitated precise monitoring of corneal healing. This case underscores the importance of prompt surgical intervention, interdisciplinary management, and vigilant long-term monitoring. Early identification and management of secondary complications, including phacolytic glaucoma, contributed to visual rehabilitation.

Letter Regarding: Corneal Endothelial Keratoprosthesis EndoArt in Patients With Glaucoma at High Risk of Graft Failure After Keratoplasty

2025-06-13

Sridevi Nair , Manpreet Kaur | Cornea

Polystyrene microplastics induces the injury of human corneal epithelial cells through ROS-mediated p53 pathway

2025-06-12

Jianfeng Long , Limin Deng , Jian Li +2 more | Mutagenesis

Abstract Objective To investigate the effects of polystyrene microplastics (PS-MPs) on human corneal epithelial cells (HCEP). Methods The cytotoxicity of PS-MPs on HCEP cells was evaluated using a CCK-8 assay … Abstract Objective To investigate the effects of polystyrene microplastics (PS-MPs) on human corneal epithelial cells (HCEP). Methods The cytotoxicity of PS-MPs on HCEP cells was evaluated using a CCK-8 assay to measure cell viability, flow cytometry to analyze cell cycle and status, immunofluorescence to detect reactive oxygen species (ROS) and γ-H2AX levels, and western blotting to assess protein expression. Results The effects of PS-MPs on HCEP cell morphology and viability were particle size- and concentration-dependent. Smaller particle sizes and higher concentrations of PS-MPs were associated with greater cytotoxicity. PS-MP exposure induced cell cycle arrest, necrosis, and apoptosis in HCEP cells, along with excessive ROS production and DNA damage. Furthermore, ROS scavengers significantly reduced PS-MP-induced ROS overproduction and DNA damage, thereby alleviating PS-MP-induced cell cycle arrest, necrosis, and apoptosis. At the molecular level, ROS scavengers reversed the PS-MP-induced changes in the expression of γ-H2AX, P53, cell cycle-related proteins (cyclin D1, CDK2, and CDK4), necrosis-related proteins (CypD, PARP-1, and SRX), and apoptosis-related proteins (Cyt C, AIF, and cleaved-caspase 3). Conclusion PS-MP exposure leads to cell cycle arrest, necrosis, and apoptosis in HCEP cells, which is associated with ROS overproduction and activation of the P53 pathway.

Risk factors for ocular graft-versus-host disease: A systematic review and meta-analysis

2025-06-05

Yuanyuan Wang , Min Yuan , Yanfei Sun +2 more | PLoS ONE

AIM Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for blood disease, and ocular graft-versus-host disease (oGVHD) is a common complication that significantly affects the quality of life … AIM Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for blood disease, and ocular graft-versus-host disease (oGVHD) is a common complication that significantly affects the quality of life of patients. Currently, the risk factors for oGVHD are still controversial.Methods To provide a scientific foundation for the prevention of oGVHD in patients undergoing allo-HSCT, studies on the factors influencing the development of oGVHD were searched in PubMed, Embase, Web of Science, Sino Med, the Cochrane Library, CIKI, the Wanfang Database, and the VIP Database from database construction to May 2024.Results Seventeen studies included 4,501 patients who received allo-HSCT, of which 1,526 were diagnosed with oGVHD, involving 22 factors. The overall prevalence of oGVHD was 37.8%.[95% CI (0.294, 0.463)].The prevalence of oGVHD based on the diagnostic criteria recommended by the National Institutes of Health was 46.7% [95% CI (0.390, 0.545)], that of the International Chronic oGVHD Group was 33.7% [95% CI (0.167, 0.506)], and that of self-defined diagnostic criteria was 32.0% [95% CI (0.184, 0.457)]. According to the meta-analysis, elderly patients [OR=1.10, 95% CI (1.00, 1.20)], female donors [OR=1.48, 95% CI (1.20, 1.83)], matched-relative donors (MRD) [OR=1.50, 95% CI (1.22, 1.83)], peripheral hematopoietic stem cells (PBSCs) [OR=1.81, 95% CI (1.38, 2.39)], acute graft-versus-host disease (aGVHD) [OR=1.74, 95% CI (1.29, 2.35)], chronic graft-versus-host disease (cGVHD) [OR=3.04, 95% CI (1.82, 5.08)], oral [OR=13.83, 95% CI (5.09, 37.56)] and skin graft-versus-host disease (GVHD) [OR=5.55, 95% CI (2.41,12.79)] were risk factors for the development of oGVHD (P < 0.0 5).Conclusion According to our systematic review and meta-analysis, the factors listed above are associated with oGVHD and can serve as early warning signs for clinicians in identifying high-risk populations eligible for early intervention and treatment.

Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing

2025-06-03

Masahito Yoshihara , Rei Kamuro , Susumu Hara +6 more | The Ocular Surface

Use of human and animal amniotic membranes in local antibiotic therapy

2025-06-02

Agnieszka Klama‐Baryła , Anna Sitkowska , Ewa Tomanek +5 more | Journal of Wound Care

Objective: The antibacterial properties of amniotic membranes are the reason for their wide clinical use. Amniotic membrane soaked in antibiotics can be used in local antibiotic therapy, creating new options … Objective: The antibacterial properties of amniotic membranes are the reason for their wide clinical use. Amniotic membrane soaked in antibiotics can be used in local antibiotic therapy, creating new options for the treatment of infections. The aim of this study was to analyse the inhibiting effect of both human and porcine amniotic membranes soaked in antibiotics on the growth of microorganisms. Method: Human and porcine placentas were collected during natural births, under aseptic conditions. Each amnion was divided into three parts: intravital; cryopreserved; and radio-sterilised. Discs of 8mm in diameter were cut from the amniotic membrane. The discs were incubated in antibiotics (gentamicin, neomycin sulfate and colistin) for three hours and then subjected to microbiological tests to assess the inhibition of bacterial growth. The inhibiting effect on microorganisms—Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae— were examined. Results: The findings of the study showed that porcine amniotic membrane was as effective in carrying antibiotics as human amnion. The ability of cryopreserved or radio-sterilised amniotic membrane to inhibit the growth of microorganisms was not reduced compared to that of fresh amnion. There was a statistically significant difference in the studied groups. The highest growth inhibition efficacy was noted for Escherichia coli, meticilin-sensitive Staphylococcus aureus, Acinetobacter baumannii-sensitive extended-spectrum beta-lactamase. The highest mean zones of growth inhibition were obtained for gentamicin and neomycin sulfate. Conclusion: This study revealed that both human and porcine amniotic membranes can be used in carrying antibiotics. Differently prepared amniotic membrane can be successfully used in microorganism inhibition.

Adjuvant Use of Topical 0.05% Cyclosporine A in Primary Pterygium Recurrence Rate: A Systematic Review and Meta-Analysis

2025-06-01

Yuri Aleksander-Ivanov , Lídia Cheidde , Davi Veiga +2 more | American Journal of Ophthalmology