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Introduction: Conjunctival and limbal stem cell deficiency (LSCD) cause decompensation of the ocular surface. Besides causing poor vision and chronic pain, these conditions remain a challenge to rehabilitate. Areas covered: The goal of this review was to describe surgical techniques to aid in reconstructing the ocular surface. Acute treatments (i.e. amniotic membrane transplantation, tenonplasty) are intended to minimize inflammatory damage and prevent sequelae. Partial LSCD may be initially treated with a sectorial conjunctival epitheliectomy or ipsilateral limbal translocation. Total/near-total LSCD often requires an ocular surface stem cell transplantation (OSST) to restore the ocular surface. A mucous membrane graft or other tissue graft can help reconstruct the fornix and address dense symblephara/ankyloblephara prior to OSST. Expert opinion: There has been a burgeoning of different variations on the main OSST types with a trend toward combined procedures, harvesting smaller amounts of either limbal or mucosal tissue, and utilizing autologous non-limbal stem cell (i.e. oral mucosal conjunctival) tissue on the corneal surface. We are cautiously optimistic as we await intermediate-term and long-term results to be published. While we note resistance among corneal specialists to perform these treatments, we hope that increased exposure in training and knowledge of these procedures' success will increase adoption. [ABSTRACT FROM AUTHOR]

Background: Human amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues. Methods and results: In this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs' tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro. Conclusions: In conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications. [ABSTRACT FROM AUTHOR]

Abstract Background Human amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues. Methods and results In this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs’ tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro. Conclusions In conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications.

Introduction: Oral epithelial cells were recently shown to be able to differentiate into corneal epithelium, and the efficacy of cultured autologous oral mucosal epithelial cells (CAOMEC) has been suggested by the presence of epithelium replacement. Therefore, the aim of this study was to evaluate the treatment outcome in limbal stem cell deficiency (LSCD) by adding CAOMEC to regular amniotic membrane (AM) treatment. Material and methods: Eyes with LSCD were randomized to two groups to undergo either autologous oral mucosal epithelial cell sheet (CAOMECS) combined with AM transplantation (A group) or AM transplantation alone (B group). Clinical outcome measures were corneal epithelium healing, best corrected visual acuity, symblepharon, corneal transparency, corneal neovascularization and ocular surface inflammation. Results: The normal corneal epithelialization rate in group A (73.33%) was higher than that in group B (35.48%), and the average healing time was shorter (3.45 ±2.12 weeks vs. 4.64 ±1.63 weeks). The symblepharon in the above two groups was improved in the first 3 months after surgery, but after 6 months, part of the B group had recurrence. In improving corneal transparency, group A has obvious advantages. Corneal neovascularization (CNV) was improved to some extent in the first 3 months after surgery, but group A (1.47 ±0.64) was better than group B (1.94 ±0.85) after 6 months. Both groups can improve the inflammatory state to some extent. Conclusions: The transplantation of CAOMECS offers a viable and safe alternative in the reconstruction of a stable ocular surface. The effect is better than that of traditional AM transplantation, mainly in promoting corneal epithelialization, improving ocular surface structure, and reducing fiber and vascular infiltration. [ABSTRACT FROM AUTHOR]

Background: Limbal stem cell deficiency (LCSD) presents several challenges. Currently, there is no clearly defined systematic approach to LSCD diagnosis that may guide surgical tactics. Methods: The medical records of 34 patients with LSCD were analyzed. Diagnostic modalities included standard (visometry, tonometry, visual field testing, slit-lamp biomicroscopy with corneal fluorescein staining, Schirmer test 1, ultrasonography) and advanced ophthalmic examination methods such as anterior segment optical coherence tomography, in vivo confocal microscopy, impression cytology, and enzyme-linked immunoassay. Results: Standard ophthalmological examination was sufficient to establish the diagnosis of LSCD in 20 (58.8%) cases, whereas advanced evaluation was needed in 14 (41.2%) cases. Depending on the results, patients with unilateral LSCD were scheduled to undergo glueless simple limbal epithelial transplantation (G-SLET) or simultaneous G-SLET and lamellar keratoplasty. Patients with bilateral LSCD with normal or increased corneal thickness were enrolled in the paralimbal oral mucosa epithelium transplantation (pLOMET) clinical trial. Conclusions: Based on the diagnostic and surgical data analyzed, the key points in LSCD diagnosis were identified, helping to guide the surgeon in selecting the appropriate surgical procedure. Finally, we proposed a novel step-by-step diagnostic algorithm and original surgical guidelines for the treatment of patients with LSCD. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects on adhesive and structural properties of newer preservation conditions to those obtained with an established, standardized protocol (dimethyl sulfoxide at −180 °C). In attempt to simplify and enhance the safety of the procedure, we tested dextran-based freezing medium and a dry condition (no medium) at temperatures of −80 °C. Methods: Five patches of human amniotic membrane were obtained from three different donors. For each donor, five preservation condition were tested: dimethyl sulfoxide at −180 °C, dimethyl sulfoxide at −80 °C, dextran-based medium at −180 °C, dextran-based medium at −80 °C and dry freezing at −80 °C (no medium). At the end of four months storage period, adhesive properties and structure were analyzed. Results: None of the newer preservation protocols showed differences in adhesive and structural properties of the tissues. The stromal layer always kept its adhesiveness, while both structure and basement membrane were not altered by any the preservation protocol. Conclusions: Switching from liquid nitrogen cryopreservation to −80 °C would reduce manipulation, simplify the procedure, making it also cheaper. The use of dextran-based freezing medium or no medium at all (dry condition) would avoid the potential toxicity of the dimethyl sulfoxide-based freezing media. [ABSTRACT FROM AUTHOR]

Conjunctival defects severely impair ocular surface homeostasis and vision. However, the existing conjunctival reconstruction methods are still unable to achieve satisfactory functional replacement of conjunctiva. Scaffold materials that provide a more stem-cell-friendly microenvironment are in urgent need of improvement. Herein we reported a functional conjunctival reconstruction scaffold constructed from decellularized matrix derived from rabbit subconjunctival fibroblasts (DM-SCF) loaded with conjunctival epithelial stem cells (CjESCs) for ocular surface repair. The DM-SCF had a thickness and mechanical strength close to that of normal conjunctiva and showed excellent biocompatibility. CjESCs inoculated on DM-SCF maintained good stem cell properties, which showed long-term maintenance of low differentiation and good proliferation activity. DM-SCF transplantation with CjESCs showed satisfactory results in rabbit models of a large conjunctival defect. The conjunctiva was reconstructed with abundant goblet cell expression and regular fiber arrangement. Protein mass spectrometry revealed the active extracellular matrix components of DM-SCF, regulating the activation of Wnt/β-catenin and Notch pathways for stem cell maintenance. Overall, our study developed a promising new strategy for ocular surface reconstruction by optimizing bioactive scaffold and providing functional stem cell niche, so as to achieve long-standing and superior functional repair.

The conjunctiva covers the largest area of ocular surface and is responsible for tear balance and clear vision. After trauma or surgery, the conjunctiva is prone to scarring and contracture. Transplantation with suture often implies numerous complications, such as inflammation, suture erosion, granuloma. And the suture needs to be removed, which means a secondary trauma. In this study, a bioadhesive hydrogel (GMO) for sutureless conjunctival transplantation was developed based on a semi-interpenetrating polymer network (sIPN) consisting of gelatin methacrylate (GelMA) and oxidized hyaluronic acid (OHA). The maximum adhesion strength was 157 ± 17 kPa, and the burst pressure was 357 ± 29 kPa, which was 15 times higher than the human intraocular pressure (IOP). GMO bioadhesive hydrogel significantly improved surgical efficiency and secured the collagen scaffold firmly to a rabbit conjunctival defect. The sutureless transplantation approach revealed the promoted tissue repair without scar. In conclusion, GMO bioadhesive may be an attractive alternative to suture for ocular surface reconstruction by avoiding suture-related complications and improving clinical outcome. Conjunctival tissue is prone to scarring and contracture after trauma, and surgery with sutures often implies numerous complications. In this study, the ocular surface reconstruction was achieved by sutureless transplantation of conjunctival scaffold using bioadhesive hydrogel. The prepared GMO bioadhesive based on the semi-interpenetrating network of gelatin methacrylate (GelMA) and oxidized hyaluronic acid (OHA) had favorable adhesion and mechanical properties. The sutureless transplantation approach significantly improved the operation efficiency, avoided suture-related complications, and promoted the regeneration of conjunctiva. This study highlights the great potential of the sutureless repair strategy for clinical application in ocular surface reconstruction. [Display omitted] [ABSTRACT FROM AUTHOR]

Amniotic membrane transplantation is commonly employed in ophthalmology to mend corneal epithelial and stromal defects. Its effectiveness in restoring the ocular surface has been widely acknowledged in clinical practice. Nevertheless, there is ongoing debate regarding the comparative effectiveness of using fresh amniotic membranes versus preserved ones. The objective of this meta-analysis was to ascertain whether there is a disparity in the effectiveness of fresh versus preserved amniotic membrane in the restoration of the ocular surface in clinical practice. The study utilized the following keywords: "fresh amniotic membrane," "preserved amniotic membrane," "amniotic membrane transplantation," and "ocular surface reconstruction." The study conducted a comprehensive search for relevant studies published until April 18, 2024. Seven different databases, namely PubMed, Web of Science, Embase, Cochrane, China Knowledge, China Science and Technology Journal VIP database, and Wanfang database, were utilized. The search was performed using the keywords "fresh amniotic membrane," "preserved amniotic membrane," "amniotic membrane transplantation," and "ocular surface reconstruction." The process of literature review and data extraction was carried out separately by two researchers, and all statistical analyses were conducted using Review Manager 5.4.1. The final analysis comprised nine cohort studies, encompassing a total of 408 participants. The statistics included six outcome indicators: visual acuity (relative risk [RR] = 1.07, 95% confidence interval [CI] = 0.93-1.24, I 2 = 0); amniotic membrane viability (RR = 1.00, 95% CI = 0.93-1.08, I 2 = 0); ocular congestion resolution (RR = 1.11, 95% CI = 0.97-1.26, I 2 = 0); fluorescent staining of amniotic membranes on the second day after the operation (RR = 1.31, 95% CI = 0.80-2.14, I 2 = 11); postoperative recurrence rate (RR = 1.01, 95% CI = 0.50-2.03, I 2 = 0); and premature lysis of amniotic membrane implants (RR = 0.96, 95% CI = 0.49-1.88, I 2 = 0). The findings indicated that there was no statistically significant disparity between fresh and preserved amniotic membranes across any of the measured variables. There is no substantial disparity in the effectiveness of fresh and preserved amniotic membrane transplants in restoring the ocular surface, and both yield favorable and consistent outcomes.

Introduction Oral epithelial cells were recently shown to be able to differentiate into corneal epithelium, and the efficacy of cultured autologous oral mucosal epithelial cells (CAOMEC) has been suggested by the presence of epithelium replacement. Therefore, the aim of this study was to evaluate the treatment outcome in limbal stem cell deficiency (LSCD) by adding CAOMEC to regular amniotic membrane (AM) treatment. Material and methods Eyes with LSCD were randomized to two groups to undergo either autologous oral mucosal epithelial cell sheet (CAOMECS) combined with AM transplantation (A group) or AM transplantation alone (B group). Clinical outcome measures were corneal epithelium healing, best corrected visual acuity, symblepharon, corneal transparency, corneal neovascularization and ocular surface inflammation. Results The normal corneal epithelialization rate in group A (73.33%) was higher than that in group B (35.48%), and the average healing time was shorter (3.45 ±2.12 weeks vs. 4.64 ±1.63 weeks). The symblepharon in the above two groups was improved in the first 3 months after surgery, but after 6 months, part of the B group had recurrence. In improving corneal transparency, group A has obvious advantages. Corneal neovascularization (CNV) was improved to some extent in the first 3 months after surgery, but group A (1.47 ±0.64) was better than group B (1.94 ±0.85) after 6 months. Both groups can improve the inflammatory state to some extent. Conclusions The transplantation of CAOMECS offers a viable and safe alternative in the reconstruction of a stable ocular surface. The effect is better than that of traditional AM transplantation, mainly in promoting corneal epithelialization, improving ocular surface structure, and reducing fiber and vascular infiltration.

The review presents an analysis of clinical trials results for autologous cultured oral mucosal epithelium transplantation (COMET) in patients with bilateral corneal limbal stem cell deficiency (LSCD) over the past 15 years. Detailed characteristics and evaluation are given for anatomical outcomes, visual acuity changes, and complication rates. The results obtained during the analysis confirm the consistency of the concept of corneal re-epithelization by means of COMET. COMET promoted persistent corneal re-epithelization in 81.5% of cases, and visual acuity improvement in 78.8% of patients with LSCD. COMET does not require systemic immunosuppression, and it is accompanied by much smaller numbers and significantly lower grades of complications compared with keratoprosthesis. About 15% of patients experienced developing superficial peripheral corneal neovascularization regressed spontaneously by 12 months of observation. Based on the COMET clinical trials results, the management of patients with bilateral LSCD is under optimization by reference to the pathogenesis of the underlying disease. Thus, autologous cultured oral mucosal epithelium transplantation seems promising for further studies and introduction into routine clinical practice.

Background: Limbal stem cell deficiency (LCSD) presents several challenges. Currently, there is no clearly defined systematic approach to LSCD diagnosis that may guide surgical tactics. Methods: The medical records of 34 patients with LSCD were analyzed. Diagnostic modalities included standard (visometry, tonometry, visual field testing, slit-lamp biomicroscopy with corneal fluorescein staining, Schirmer test 1, ultrasonography) and advanced ophthalmic examination methods such as anterior segment optical coherence tomography, in vivo confocal microscopy, impression cytology, and enzyme-linked immunoassay. Results: Standard ophthalmological examination was sufficient to establish the diagnosis of LSCD in 20 (58.8%) cases, whereas advanced evaluation was needed in 14 (41.2%) cases. Depending on the results, patients with unilateral LSCD were scheduled to undergo glueless simple limbal epithelial transplantation (G-SLET) or simultaneous G-SLET and lamellar keratoplasty. Patients with bilateral LSCD with normal or increased corneal thickness were enrolled in the paralimbal oral mucosa epithelium transplantation (pLOMET) clinical trial. Conclusions: Based on the diagnostic and surgical data analyzed, the key points in LSCD diagnosis were identified, helping to guide the surgeon in selecting the appropriate surgical procedure. Finally, we proposed a novel step-by-step diagnostic algorithm and original surgical guidelines for the treatment of patients with LSCD.

Limbal stem cell deficiency (LSCD) is a very challenging situation and difficult to manage. A great works and ideas were conducted over the past 50 years. Numerous surgical techniques were proposed. We are reporting more than a 20-year follow-up of a case of limbal autograft stem cell transplantation due to LSCD secondary to chemical injury. [ABSTRACT FROM AUTHOR]

The in vitro reconstruction of stromal tissue by long‐term cultivation of corneal fibroblasts is a smart approach for regenerative therapies of ocular surface diseases. However, systematic investigations evaluating optimized cultivation protocols for the realization of a biomaterial are lacking. This study investigated the influence of supplements to the culture media of human corneal fibroblasts on the formation of a cell sheet consisting of cells and extracellular matrix. Among the supplements studied are vitamin C, fetal bovine serum, L‐glutamine, components of collagen such as L‐proline, L‐4‐hydroxyproline and glycine, and TGF‐β1, bFGF, IGF‐2, PDGF‐BB and insulin. After long‐term cultivation, the proliferation, collagen and glycosaminoglycan content and light transmission of the cell sheets were examined. Biomechanical properties were investigated by tensile tests and the ultrastructure was characterized by electron microscopy, small‐angle X‐ray scattering, antibody staining and ELISA. The synthesis of extracellular matrix was significantly increased by cultivation with insulin or TGF‐β1, each with vitamin C. The sheets exhibited a high transparency and suitable material properties. The production of a transparent, scaffold‐free, potentially autologous, in vitro‐generated construct by culturing fibroblasts with extracellular matrix synthesis‐stimulating supplements represents a promising approach for a biomaterial that can be used for ocular surface reconstruction in slowly progressing diseases. [ABSTRACT FROM AUTHOR]

Purpose: Presentation of a rare case of a congenital tumor: a case of a giant extended epibulbar dermoid. Observation: 19-month-old girl with a history of consanguinity of the parents and an unattended pregnancy, the patient presents a bourgeoning tumor, bilobed, fixed to the left eyeball extended to the inferomedial conjunctiva and limbus. The patient underwent a tumor removal with reconstruction of the ocular surface by grafting her oral mucosa. The anatomopathological study revealed an epibulbar dermoid. Conclusions and importance: We present a rare case of extensive epubulbar dermoid isolated in a young pediatric patient. The management of this type of anomaly must be early, and includes the search for any anomalies in favor of a specific syndrome which, if neglected, may engage the functional and/or vital prognosis.

Abstract The conjunctiva is a clear tissue covering the white part of the eye and lines the back of the eyelids. Conjunctival diseases, such as symblepharon, cause inflammation, discharges, and photophobia. The treatment often requires excision of large parts of conjunctiva. Tissue engineering of conjunctival cells using human amniotic membrane (HAM) denuded of its epithelium as a basement membrane scaffold has been shown to be effective for covering conjunctival defects. However, most epithelial denudation protocols are time‐consuming and expensive or compromise HAM's basement membrane structure and matrix components. We have previously described a method to de‐epithelialize HAM using ice‐cold urea (uHAM). In this report, we used this method to provide tissue‐engineered constructs with cultivated conjunctival epithelial cells on uHAM in two patients, one with a giant conjunctival nevus and the other with a large symblepharon. Autologous conjunctival epithelial cells harvested from incisional biopsies of these two patients were cultured on the uHAM scaffold. The transplantation of tissue‐engineered constructs to patients' ocular surface immediately after the removal of lesions showed successful reconstruction of the ocular surface. Postoperatively, there were neither recurrence of lesions nor epithelial defects throughout the follow‐up (up to 7 and 19 months, respectively). This report highlights the translational potential of an efficient and inexpensive method to prepare de‐epithelialized HAM as a basement membrane scaffold for cell‐based tissue‐engineered treatments of ocular surface disorders. Stem Cells Translational Medicine 2019;8:620&626

The review presents a new surgical approach and its clinical results for corneal epithelial reconstruction in patients with unilateral limbal stem cell deficiency (LSCD) of burn etiology. Simple limbal epithelial transplantation (SLET) is a novel surgical technique of limbal transplantation.SLET uses the healthy eye as a donor source for dissection of a 2×2 mm strip of limbal tissue, gluing an amniotic membrane after preparation the recipient contralateral ocular surface, distributing and gluing eight to ten small pieces of limbal tissue over an amniotic membrane. The new type of grafting utilizes tissue-preserving approach and as effective as transplantation of cultivated autologous limbal epithelial stem cells. Clinical finding demonstrated its efficiency, safety, and reproducibility. SLET provides a long-term reconstruction of the corneal epithelium for patients with unilateral LSCD in approximately 72-80% and a visual acuity improvement 72-75% of appropriately selected patients depending on age and eye co-morbidity.

Purpose: To report the surgical management of extensive epibulbar dermoids with autologous oral mucous membrane transplantation. Observations: While rare, extensive dermoids that encroach upon the visual axis carry a poor prognosis. We report the case of a 7-week old premature male infant who presented with large bilateral epibulbar dermoids obscuring the visual axis. He was treated first with sequential bilateral optical iridectomies under the clearest corneal areas, followed several months later by sequential dermoid excision and amniotic membrane transplantation in each eye. He subsequently underwent autologous “simple” oral mucosal epithelial transplantation (SOMET) as well as strabismus surgery. Conclusions and Importance: Here we present the first case, to the best of our knowledge, of the use of SOMET in managing post-operative pseudopterygium following dermoid excision. To our knowledge it is the also the first application of this technique in a young pediatric patient. A good clinical outcome may be achieved with SOMET, which may offer a minimally invasive alternative to other traditional modalities.

Tobias Röck,1 Hans-Christian Bösmüller,2 Karl Ulrich Bartz-Schmidt,1 Daniel Röck1 1Centre for Ophthalmology, University of Tübingen, Tübingen, Germany; 2Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany Purpose: Nevi of the conjunctiva are usually benign pigmented tumorous lesions located in the bulbar conjunctiva. In most conjunctival nevus cases, the patient wants the lesion to be removed for cosmetic reasons, but excisional biopsies are best for lesions suspicious for malignancy. This case report illustrates the intraoperative surgical management, histological findings, and the course of healing in a conjunctival nevus patient. Case report: A 26-year-old man was referred to our eye hospital with a large bulbar conjunctival nevus of the right eye. Upon examination, there was a large pigmented lesion with numerous small cysts present on the superior bulbar conjunctiva. The conjunctival tumor was resected, and an amniotic membrane transplantation was performed for the bulbar conjunctival reconstruction. The histopathological diagnosis suggested a conjunctival nevus. After the resection, a reduction in the inflammation and healing of the conjunctival lesion could be seen. The epithelialization of the bulbar conjunctiva over the amniotic membrane was complete 4 weeks after the resection. At the 6-month follow-up, there was no sign of recurrence or any postoperative complications. Conclusion: A surgical excision combined with reconstruction via amniotic membrane transplantation is effective and economical for the treatment of large conjunctival lesions. Keywords: conjunctival nevus, reconstructive surgical procedures, amniotic membrane transplantation, ocular surface reconstruction

The purpose of this paper is to illustrate a case of large conjunctival nevus in a 10-yearold boy which was successfully treated with surgical excision and amniotic membrane transplant (AMT) reconstruction. The conjunctival nevus was initially noticed by the parents 1 year prior to presentation; they reported it had increased in size over the past 3 months. Slit-lamp examination revealed a pigmented conjunctival nevus measuring 5.5 mm vertically and 6.5 mm horizontally, with well-demarcated margins and presence of an intralesional cyst at the temporal bulbar conjunctiva, involving the limbus and encroaching onto the cornea. Complete resection of the conjunctival lesion and bulbar conjunctival reconstruction were performed. The histopathological examination showed conjunctival nevus. The wound healed well with vision of 6/6 and no recurrence. Surgical resection combined with AMT is a successful and an effective way to treat conjunctival nevus. [ABSTRACT FROM AUTHOR]

Purpose: A hyper-dry amniotic membrane (HDAM) has been used clinically for ocular surface reconstruction, but sufficient evidence of the histological dynamics and long-term safety have not been obtained. We examined the histological changes in an HDAM after its subconjunctival implantation in rabbit eyes, and we compared these changes to those in the Ambio2TM Amniotic Membrane Graft (IOP Ophthalmics, Costa Mesa, CA, USA) after the same surgery. Design: A prospective controlled animal study. Methods: We used 27 rabbits in two groups: the HDAM group (36 eyes of 18 rabbits) and the Ambio2 group (18 eyes of 9 rabbits). The HDAM or Ambio2 was transplanted on the bare sclera and covered with a conjunctival autograft. The histological changes were determined by evaluating the amniotic membrane graft, inflammatory cells, and foreign body granulomas in hematoxylin/eosin-stained sections at 30 days, 93 days, and 184 days postoperatively. Results: In all cases, the amniotic membrane graft was completely absorbed without scarring at 184 days postoperatively. The positive rate of inflammatory cells was significantly higher in the HDAM group compared to the Ambio2 group at 30 days postoperatively. The positive rate of foreign body granulomas decreased with time, with no significant difference between the two groups. Conclusions: Both the HDAM and Ambio2 were completely absorbed without scarring within 6 months after surgery. The two types of membranes showed histologically equivalent responses. Translational Relevance: Since the HDAM was completely absorbed without scarring within 6 months after surgery, we could confirm its long-term safety. [ABSTRACT FROM AUTHOR]

Various ocular surface disorders like alkali burns and corneal ulcers can all cause damage to the cornea and conjunctiva, and often induce corneal neovascularization(CNV)that affects the visual function. However, amniotic membranes(AM)can promote the rapid epithelization of acute injured corneas and conjunctiva defects, diminish scarring, and perform anti-inflammatory effect. Therefore, AM has been widely used in ocular surface reconstructions and treatment of CNV. But the key problem is how to fix the AM. Only ensuring the adhesive time and cover area with convenient operation and little stimulation can achieve the best curative effect. This article reviews the methods of AM fixation in AM patch technique.

Limbal stem cells (SCs) represent a key component of the corneal-conjunctival barrier and play a vital role in the regeneration and replacement of the corneal epithelium. These SCs are located in the basal region of the limbus, in the palisades of Vogt.Limbal SCs may be lost in a wide variety of conditions, the most common being chemical injury, thermal burns, Stevens-Johnson syndrome (SJS), and vernal keratoconjunctivitis. Limbal SC deficiency (LSCD) may result in a painful and blinding ocular surface disorder leading to epithelial defects and conjunctivilization of the cornea. The management of LSCD depends primarily on the laterality, extent of involvement of the eye, and the condition of the other eye. Amniotic membrane transplantation is an established technique used in acute stage to minimize the primary insult and prevent the development of LSCD. In cases of established LSCD, transplanted tissue may be derived from autologous or allogenic sources. Long-term results of cultured limbal epithelial stem cell transplant have demonstrated greater therapeutic success when compared to previous forms of treatment. Moreover, with the help of advances in microsurgical techniques and immunosuppressant drugs, clinical assessment of the outcome of ocular surface rehabilitative procedures grows increasingly optimistic. This article describes the role of SCs in corneal epithelial regeneration, as well as the etiology and clinical features of LSCD.

A 26-year-old male was referred with sequel of Stevens-Johnson Syndrome (SJS) in form of bilateral severe keratinisation of lid margin and Symbhlepharon involving in particular forniceal region. At the time of presentation his visual acuity was 20/120. Indirect ophthalmoscopic examination revealed normal optic nerve head with attached retina. Superficial dissection was done between palpebral and bulbar conjunctiva so as to release symblepharon and further ocular surface reconstruction was carried out with labial Mucous Membrane Graft [MMG]. His best corrected final visual acuity was 20/40 with well accepted graft indicating that this technique definitely improves visual acuity and alleviates patient discomfort by improving ocular surface milieu and hence, possibly further avoids deterioration of ocular surface in SJS.

AIM: To evaluate the clinical effect of vitamin A palmitate eye gel on early ocular surface reconstruction after thermal or chemical injuries. METHODS: Seventy-eight cases with thermal or chemical injuries to eyes were selected and divided into two groups by randomized, double-blind, positive drug parallel controlled method: group A(40 cases were treated with vitamin A palmitate eye gel)and group B \〖38 cases were treated with basic fibroblast growth factor(bFGF)\〗. The bFGF and vitamin A palmitate eye gel were used 4 times a day. The treatment course was 14d. Restoration of epithelial defect, Schirmer's test values, tear break-up time(BUT), and subjective assessment of symptoms and signs were observed on D1, D3, D5, D7, D10 and D14.RESULTS: In group A, 31 cases were cured, 5 cases were effective, with the cure rate of 76% and efficiency 90%. In group B, 32 cases were cured, 3 cases were effective, with the cure rate of 84% and efficiency 92%. There were no significant differences between the two groups(P>0.05). However, there were significant differences on the results of Schirmer's test and BUT(PPCONCLUSION: Vitamin A palmitate eye gel is valuable and safe on early ocular surface reconstruction of the eyes suffered from thermal or chemical injuries.

Limbal stem cell deficiency is commonly encountered entity in routine practice. Most of the cases go unidentified at the first visit and progress to the severe disease when the problem is actually realized. In limbal stem cell deficiency, corneal limbal stem cells fail to maintain and renew corneal epithelial surface and the corneal surface is encroached by conjunctival epithelium, compromising the transparency and visual acuity. First step in the management of limbal stem cell deficiency is early control of the ocular surface inflammation and elimination of the causative factor. Surgical intervention in terms of limbal stem cell transplantation is the definitive treatment for most of the cases. Successful limbal stem cell transplantation can achieve rapid surface healing, stable ocular surface without recurrent erosions or persistent epithelial defects, regression of corneal vascularization, and restoration of a smooth and optically improved ocular surface, resulting in improved visual acuity and probably increased success for subsequent keratoplasty. Here is a brief review covering etiology, clinical presentation, and management options for the cases of limbal stem cell deficiency.

Amniotic membrane is a unique biological product that has been in use for a myriad of bodily conditions, both ophthalmic and non-ophthalmic. However, the ophthalmic use are still increasing day by day. Its unique properties like anti-inflammatory, antimicrobial, antifibrotic, antiangiogenic and source of growth factors make it into a biological bandage which can be life-saving to the eye. Harvested from the human placenta, it has found extensive use in ocular surface reconstruction, chemical injury to the eye, corneal perforation, persistent epithelial defects, ocular surface neoplasia, pterygium surgery, trabeculectomy, glaucoma bleb repair and lid surgeries, to name a few. This article outlines in detail the properties and utility of amniotic membrane.

The aim of the study is to evaluate the long-term clinical results of amniotic membrane transplantation (AMT) combined with mitomycin C (MMC) for reconstruction of conjunctival defects created during the excision of ocular surface squamous neoplasia (OSSN). Eight consecutive eyes of seven patients (five males and two females; mean age, 64 ± 19 years) treated by one surgeon (KH) were included in this study. AMT was performed after excision of a mass region, along with 0.04 % MMC treatment for the exposed sclera. The tumor size, histopathological retrieval, AM graft size after tumor excision, recurrence, and postoperative complications were recorded. During a mean postoperative follow-up period of 60.9 ± 14.6 months (range 36-78 months), the ocular surfaces completely re-epithelialized in all cases. The median size of the tumor was 44.4 ± 21.2 mm (range 13-67 mm). The histopathological diagnoses were five cases of squamous cell carcinoma in situ (SCC in situ) and three cases of dysplasia. The median size of the AM graft after tumor excision was 100.8 ± 32.7 mm (range 49-151 mm). A case of recurrent SCC in situ with a preoperative history of using MMC eye drops developed further corneal limbal deficiency and was treated with therapeutic soft contact lenses. A case of dysplasia with a history of large pterygial excision developed symblepharon postoperatively was treated with AMT 6 months after tumor excision. The tumors recurred in two eyes with SCC in situ and were successfully treated with continuous AMT and MMC. No severe complications, such as infections, corneal or scleral thinning, or ulceration developed in all cases. The combination of AMT and MMC is effective for safe reconstruction over the long-term after the excision of OSSN with postoperative careful observation and treatment. In recurrent tumor excision cases, AMT is a suitable technique for repeated ocular surface reconstruction. [ABSTRACT FROM AUTHOR]

Circumscribed choroidal hemangiomas are rare ophthalmic entities that cause diminution in vision due to accumulation of subretinal and/or intraretinal fluid in the macular area. Various treatment options ranging from conventional laser to photodynamic therapy have been employed to destroy the tumor and reduce the exudation; however, either the inability to penetrate through the exudative fluid or the collateral retinal damage induced by these treatment modalities make them unsuitable for lesions within the macula. We evaluated the role of intravitreal bevacizumab, a pan-vascular endothelial growth factor (VEGF) inhibitor, in reducing the sub- and intraretinal fluid in three patients with circumscribed choroidal hemangiomas. All the patients had complete resolution of the serous retinal detachment that was maintained till at least 12 months after the first injection. Intravitreal bevacizumab may be used in combination with thermal laser or photodynamic therapy in treating circumscribed choroidal hemangiomas with subretinal fluid.

Pre-existing scleral pathology is an important risk factor for globe rupture during scleral buckling procedures. We report here, the surgical management of an unexpected scleral pathology found at the scleral buckling procedure in a retinal detachment patient. A 77-year-old white female with retinal detachment underwent a scleral buckling procedure. The surgery was converted into a scleral graft procedure, as extreme scleral thinning was found intraoperatively. An alcohol-preserved donor sclera graft was used. The second surgery for definitive retinal alignment was performed two weeks later. The presented case of an unexpected scleral pathology in a retinal detachment patient was managed with a combination of scleral grafting and pars plana vitrectomy, without any major complications. The anatomical outcome was excellent and the scleral rupture was prevented; the visual outcome was satisfactory. A conversion of the scleral buckling procedure into a scleral graft procedure has proved to be safe and effective for unexpected scleral pathology.

This retrospective, interventional case series analyses treatment outcomes in eyes with choroidal neovascularization (CNV) secondary to pathological myopia, managed with photodynamic therapy, (PDT), (Group 1, N = 11), PDT and intravitreal triamcinolone acetonide (4 mg/0.1ml) (Group 2, N = 3), PDT and intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab 1.25 mg/0.05 ml, ranibizumab 0.5 mg/0.05 ml and reduced-fluence PDT and intravitreal ranibizumab 0.5 mg/0.05 ml (Group 3, N=12). All the patients underwent PDT. Intravitreal injections were repeated as required. SPSS 14 software was used to evaluate the data. Wilcoxon signed ranks test was used to evaluate pre- and post-treatment vision. The Kruskal-Wallis test was used for comparison between the groups. All the groups were statistically comparable. All the eyes showed complete regression of CNV, with a minimum follow-up of six months. All groups had visual improvement; significantly in Group 3 ( p = 0.003). Combination PDT with anti-VEGF agents appeared to be efficacious in eyes with myopic CNV. However, a larger study with a longer follow-up is required to validate these results.

The most commonly used tissue substitute for ocular surface reconstruction is human amniotic membrane (AM). Because of its low biomechanical strength and intransparency there is a need to search for alternatives of consistent quality. This study, further explored the biocompatibility of Keratin Film (KF) and its ability to sustain corneal epithelial wound healing. In three equal groups of 5 New Zeeland white rabbits a 4 mm superficial keratectomy was created in the right eye. Five eyes received a KF, five a human AM graft and the remaining five no implant. All eyes were treated with ofloxacin and dexamethasone eye drops and followed up for 10 days. Corneal fluorescein staining, vascularization, and transparency were assessed using slit lamp biomicroscopy according to a standardized grading score during and at the end of follow-up. The corneal-scleral-button was excised and processed for histology. After 10 days all eyes which had received a KF showed complete epithelial healing and no signs of neovascularization. In the AM group 1 eye showed a persistent epithelial defect at day 10 and 2 eyes showed neovascularization at day 7 resolving at day 10. Transparency improved progressively both in the KF group as well as in the AM group towards the end of the follow. Histology showed a multilayer epithelium firmly adherent to the KF with no evidence of keratocyte migration or inflammatory reaction in the corneal stroma. In this study on rabbit eyes KF better supported corneal epithelial wound healing than amniotic membrane. [ABSTRACT FROM AUTHOR]

[Display omitted] • Decellularized matrix derived from subconjunctival fibroblasts (DM-SCF) obtained in situ from conjunctiva was prepared as a stem-cell-friendly scaffold. • The functional niche provided by DM-SCF facilitates stem cell maintenance through Wnt/β-catenin and Notch pathways. • DM-SCF can achieve long-term and superior functional repair of the ocular surface. Conjunctival defects severely impair ocular surface homeostasis and vision. However, the existing conjunctival reconstruction methods are still unable to achieve satisfactory functional replacement of conjunctiva. Scaffold materials that provide a more stem-cell-friendly microenvironment are in urgent need of improvement. Herein we reported a functional conjunctival reconstruction scaffold constructed from decellularized matrix derived from rabbit subconjunctival fibroblasts (DM-SCF) loaded with conjunctival epithelial stem cells (CjESCs) for ocular surface repair. The DM-SCF had a thickness and mechanical strength close to that of normal conjunctiva and showed excellent biocompatibility. CjESCs inoculated on DM-SCF maintained good stem cell properties, which showed long-term maintenance of low differentiation and good proliferation activity. DM-SCF transplantation with CjESCs showed satisfactory results in rabbit models of a large conjunctival defect. The conjunctiva was reconstructed with abundant goblet cell expression and regular fiber arrangement. Protein mass spectrometry revealed the active extracellular matrix components of DM-SCF, regulating the activation of Wnt/β-catenin and Notch pathways for stem cell maintenance. Overall, our study developed a promising new strategy for ocular surface reconstruction by optimizing bioactive scaffold and providing functional stem cell niche, so as to achieve long-standing and superior functional repair. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of amniotic membrane for treatment of partial limbal stem cell deficiency (LSCD). Methods: Medical records of four patients with partial LSCD who underwent pannus resection and amniotic membrane transplantation (AMT) were reviewed for ocular surface stability and improvement in visual acuity. Clinico-histopathological correlation was done with the resected pannus tissue. Results: All the eyes exhibited stable corneal epithelial surface by an average of 7 weeks postoperatively with improvement in subjective symptoms. Best corrected visual acuity improved from preoperative (range: 6/9p-6/120) to postoperative (range: 6/6p-6/15) by an average of 4.5 lines on Snellen visual acuity charts. Histopathological examination of excised tissue showed features of conjunctivalisation. Conclusion: Amniotic membrane transplantation appears to be an effective means of reconstructing the corneal epithelial surface and for visual rehabilitation of patients with partial limbal stem cell deficiency. It may be considered as an alternative primary procedure to limbal transplantation in these cases.

A 26-year-old male was referred with sequel of Stevens-Johnson Syndrome (SJS) in form of bilateral severe keratinisation of lid margin and Symbhlepharon involving in particular forniceal region. At the time of presentation his visual acuity was 20/120. Indirect ophthalmoscopic examination revealed normal optic nerve head with attached retina. Superficial dissection was done between palpebral and bulbar conjunctiva so as to release symblepharon and further ocular surface reconstruction was carried out with labial Mucous Membrane Graft [MMG]. His best corrected final visual acuity was 20/40 with well accepted graft indicating that this technique definitely improves visual acuity and alleviates patient discomfort by improving ocular surface milieu and hence, possibly further avoids deterioration of ocular surface in SJS. [ABSTRACT FROM AUTHOR]