Persistent Epithelial Defects Research Articles

Scleral Contact Lens for Steven-Johnson Syndrome

Background: Steven-Johnson syndrome is one of life-threatening skin abnormality. SJS complication involve multiorgan disfunction such as mucosa, ocular, respiration, and digestive tract. Around 30- 50% of SJS patient experience chronic ocular sequel, which concludes progressive symblepharon, margo palpebral keratinization, trichiasis, entropion, corneal pannus, dry eye syndrome, and persistent epithelial cornea defect. Scleral contact lenses has beneficial in managing SJS patient, on both acute and chronic phases. Methods: A 36-year-old female patient with SJS, presented for eye examination due to unpleasant sensation on both of their eyes and unsatisfactory quality of her vision. She presented high myopia, margo palpebral keratinization with trichiasis and distichiasis, symblepharon and hyperemic conjunctiva, wide corneal scar, and ocular neovascularization. A diagnostic trial set was used in the fitting process, and she was assessed according to standardized fitting methodology. Visual acuity, corneal topography, biometry, and ocular aberrations were evaluated. The follow-up period was 12 months. Results: The best corrected visual acuity was 20/60 with correction lens S – 1.00 D for the left eye (LE) and 20/25 cannot be corrected with correction lens for the right eye (RE). After corneal contact lens fitting, visual acuity was improved to 20/20 and 20/25 for the RE and LE, respectively. The patient wore these contact lenses an average 8 hours a day. The patient’s dry eye complaint was significantly decrease with more comfortable ocular sensation Conclusion: The present case report describes how the patient had scleral contact lens fitted successfully for management of SJS ocular complication. They provided optimal visual quality and restore the patient’s comfort.

Topical Losartan: Practical Guidance for Clinical Trials in the Prevention and Treatment of Corneal Scarring Fibrosis and Other Eye Diseases and Disorders.

Losartan is an angiotensin II receptor blocker (ARB) that impedes transforming growth factor (TGF) beta signaling by inhibiting activation of signal transduction molecule extracellular signal-regulated kinase (ERK). Studies supported the efficacy of topical losartan in decreasing scarring fibrosis after rabbit Descemetorhexis, alkali burn, and photorefractive keratectomy injuries, and in case reports of humans with scarring fibrosis after surgical complications. Clinical studies are needed to explore the efficacy and safety of topical losartan in the prevention and treatment of corneal scarring fibrosis, and other eye diseases and disorders where TGF beta has a role in pathophysiology. These include scarring fibrosis associated with corneal trauma, chemical burns, infections, surgical complications, and persistent epithelial defects, as well as conjunctival fibrotic diseases, such as ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Research is also needed to explore the efficacy and safety of topical losartan for hypothesized treatment of transforming growth factor beta-induced (TGFBI)-related corneal dystrophies (Reis-Bu¨cklers corneal dystrophy, lattice corneal dystrophy type 1, and granular corneal dystrophies type 1 and type 2) where deposited mutant protein expression is modulated by TGF beta. Investigations could also explore the efficacy and safety of topical losartan treatments to reduce conjunctival bleb scarring and shunt encapsulation following glaucoma surgical procedures. Losartan and sustained release drug delivery devices could be efficacious in treating intraocular fibrotic diseases. Dosing suggestions and precautions that should be considered in trials of losartan are detailed. Losartan, as an adjuvant to current treatments, has the potential to augment pharmacological therapeutics for many ocular diseases and disorders where TGF beta plays a central role in pathophysiology.

An electrospun scaffold functionalized with a ROS-scavenging hydrogel stimulates ocular wound healing.

Ocular alkali burn is a serious ophthalmic emergency. Highly penetrative alkalis cause strong inflammatory responses leading to persistent epithelial defects, acute corneal perforation and severe scarring, and thereby persistent pain, loss of vision and cicatricial sequelae. Early and effective anti-inflammation management is vital in reducing the severity of injury. In this study, a double network biomaterial was prepared by compounding electrospinning nanofibres of thioketal-containing polyurethane (PUTK) with a reactive oxygen species (ROS)-scavenging hydrogel (RH) fabricated by crosslinking poly(poly(ethylene glycol) methyl ether methacrylate-co-glycidyl methacrylate) with thioketal diamine and 3,3'-dithiobis(propionohydrazide). The developed PUTK/RH patch exhibited good transparency, high tensile strength and increased hydrophilicity. Most importantly, it demonstrated strong antioxidant activity against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH). Next, a rat corneal alkali burn model was established, and the PUTK/RH patch was transplanted on the injured cornea. Reduced inflammatory cell infiltration was revealed by confocal microscopy, and lower expression levels of genes relative to inflammation, vascularization and scarring were identified by qRT-PCR and western blot. Fluorescein sodium dyeing, hematoxylin and eosin (H&E) staining and immunohistochemicalstaining confirmed that the PUTK/RH patch could accelerate corneal wound healing by inhibiting inflammation, promoting epithelial regeneration and decreasing scar formation. STATEMENT OF SIGNIFICANCE: Ocular alkali burn is a serious ophthalmic emergency, characterized with persistent inflammation and irreversible vision loss. Oxidative stress is the main pathological process at the acute inflammatory stage, during which combined use of glucocorticoids and amniotic membrane transplantation is the most widely accepted treatment. In this study, we fabricated a polyurethane electrospun nanofiber membrane functionalized with a ROS-scavenging hydrogel. This composite patch could be a promising amniotic membrane substitute, possessing with a transparent appearance, elasticity and anti-inflammation effect. It could be easily transplanted onto the alkali-burned corneas, resulting in a significant inhibition of stromal inflammation and accelerating the recovery of corneal transparency. The conception of ROS-scavenging wound patch may offer a new way for ocular alkali burn.

Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED).

Purpose: Failure of rapid re-epithelialization within 10-14 days after corneal injury, even with standard supportive treatment, is referred to as persistent corneal epithelial (CE) defect (PED). Though an array of genes regulates reepithelization, their mechanisms are poorly understood. We sought to understand the network of genes driving the re-epithelialization in PED. Method: After obtaining informed consent, patients underwent an ophthalmic examination. Epithelial scrapes and tears samples of six PED patients and six individuals (control) undergoing photorefractive keratectomy (PRK) were collected. RNA isolation and quantification were performed using either the epithelial scrape taken from PED patients or from HCLE cells treated with control tears or tears of PED patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of a few important genes in CE homeostasis, inflammation, and cell-cell communication, viz., Kruppel-like factor 4 (KLF4), GPX4, IL6, TNFα, STING, IL8, desmoglein, and E-cadherin, among others. Their expressions were normalized with their respective housekeeping genes and fold changes were recorded. KLF4 localization and MMPs activity was carried out via immunofluorescence and zymography, respectively. Results: KLF4, a transcription factor important for CE homeostasis, was upregulated in tears-treated HCLE cells and downregulated in PED patients compared to the healthy PRK group. Cell-cell communication genes were also upregulated in tears-treated cells, whereas they were downregulated in the PED tissue group. Genes involved in proinflammation (IL6, 282-fold; TNFα, 43-fold; IL8, 4.2-fold) were highly upregulated in both conditions. MMP9 activity increased upon tears treatment. Conclusions: This study suggests that tears create an acute proinflammatory milieu driving the PED disease pathology, whereas the PED patients scrapes are an indicator of the chronic stage of the disease. Interferons, pro-inflammatory genes, and their pathways are involved in PED, which can be a potential target for inducing epithelialization of the cornea.

Etiology-Specific Comparison of the Long-Term Clinical Outcome of Repeat Deep Anterior Lamellar Keratoplasty for Optical Indications.

The aim of this study was to evaluate the etiology-specific clinical outcomes and complications of repeat deep anterior lamellar keratoplasty (DALK) after failed DALK. This retrospective case study included 32 eyes of 27 patients who underwent repeat DALK of 450 cases of DALK performed for optical indications between 1997 and 2013. The patients were divided into 4 etiology-specific subgroups (the corneal dystrophy, ocular surface disease, stromal scar, and others) or those with or without limbal stem cell deficiency (LSCD). The clinical outcomes evaluated were graft survival, best-corrected visual acuity, endothelial cell density, and complications. The mean postoperative follow-up duration was 69.6 ± 54.8 months. The 1-, 3-, and 5-year overall graft survival rate were 76.7%, 57.5%, and 38.8% respectively. The graft survival rate was the highest in the corneal dystrophy group ( P = 0.0014) and was significantly ( P = 0.0010) higher in eyes without LSCD than in eyes with LSCD. There were no significant differences in the graft survival rates between the previous and current DALK groups. The postoperative best-corrected visual acuity of all subjects improved significantly. The postoperative endothelial cell density did not decrease after repeat DALK. There were no significant differences in the incidence of complications between patients with and without LSCD, except the incidence of persistent epithelial defects. Repeat DALK had favorable outcomes in all etiology-specific groups, whereas eyes with LSCD required careful assessment of the ocular surface to avoid graft failure due to persistent epithelial defects.

Clinical observation of recombinant human nerve growth factor in the treatment of neurotrophic keratitis.

To characterize changes of corneal nerve morphology and tear indices in patients with neurotrophic keratitis (NK) treated with recombinant human nerve growth factor (rhNGF). In a prospective observational study, six patients (nine eyes) were locally treated with rhNGF. Visual acuity, corneal fluorescein staining score, the heights of the tear river, lipid layer thickness (LLT), tear ferning (TF) test, conjunctival impression cytology (CIC) examination, the densities of cornea subbasal nerve fibers were determined before and after treatment. Compared with baseline, there was a significant difference in corneal fluorescence staining scores (P<0.01); all patient corneal epithelial defects recovered completely within 8wk, but there was no significant improvement in the height of the tear river (P=0.202). LLT was significantly increased when compared with baseline (P=0.042); however, the function of conjunctival goblet cells and mucin content did not significantly improve using the TF test and CIC examination (P=0.557, P=0.539). After 8wk of treatment, the average corneal subbasal nerve fiber density increased significantly (P<0.01), as did the number of corneal nerve fiber branches (P=0.001). RhNGF can increase the density of corneal subbasal nerve fibers, promote the healing of persistent corneal epithelial defects and corneal ulcers in patients with NK, also improving tear function partially.

Refractory Keratolimbal Allograft Rejection in Autoimmune Polyglandular Syndrome-Associated Keratopathy Treated With Intravenous Immunoglobulin.

The aim of this study was to describe the use of intravenous immunoglobulin (IVIG) in the management of a 20-year-old woman with autoimmune polyglandular syndrome-associated keratopathy who developed acute transplant rejection after keratolimbal allograft (KLAL) surgery. Nine weeks after KLAL surgery, a 20-year-old woman with autoimmune polyglandular syndrome-related limbal stem cell deficiency presented with graft injection, hemorrhage, and an epithelial rejection line. This was concerning for acute rejection in the setting of triple-agent systemic immunosuppression (albeit nonadherence at times). There was initial reversal of the rejection process with a sub-Tenon's injection of triamcinolone, frequent topical corticosteroids, increase in oral prednisone, and optimization of systemic immunosuppression medications; however, recurrence of the epithelial rejection line and symptoms were noted whenever the prednisone dose was tapered. This was accompanied by ocular surface decompensation (late staining, neovascularization, and persistent epithelial defects). She was found to have weakly positive HLA Class 1 antibodies. The patient was treated with a pulsed corticosteroid infusion and 2 monthly IVIG infusions. This led to resolution of the acute rejection. However, there was a subsequent rejection episode 4 months later after tapering the prednisone. Monthly IVIG for 6 more months led to final resolution with successful prednisone tapering and no further rejection. Treatment with prolonged IVIG showed better improvement in a case of acute rejection refractory to traditional treatments, especially in the setting of HLA antibodies. The case demonstrates that close follow-up with a corneal specialist and collaboration with a transplant specialist is important to monitor for postoperative KLAL rejection.

Corneal stem cells niche and homeostasis impacts in regenerative medicine; concise review.

The limbal stem cells niche (LSCN) is an optimal microenvironment that provides the limbal epithelial stem cells (LESCs) and strictly regulates their proliferation and differentiation. Disturbing the LSCN homeostasis can lead to limbal stem cell dysfunction (LSCD) and subsequent ocular surface aberrations, such as corneal stromal inflammation, persistent epithelial defects, corneal neovascularisation, lymphangiogenesis, corneal opacification, and conjunctivalization. As ocular surface disorders are considered the second main cause of blindness, it becomes crucial to explore different therapeutic strategies for restoring the functions of the LSCN. A major limitation of corneal transplantation is the current shortage of donor tissue to meet the requirements worldwide. In this context, it becomes mandatory to find an alternative regenerative medicine, such as using cultured limbal epithelial/stromal stem cells, inducing the production of corneal like cells by using other sources of stem cells, and using tissue engineering methods aiming to produce the three-dimensional (3D) printed cornea. Limbal epithelial stem cells have been considered the magic potion for eye treatment. Epithelial and stromal stem cells in the limbal niche hold the responsibility of replenishing the corneal epithelium. These stem cells are being used for transplantation to maintain corneal epithelial integrity and ultimately sustain optimal vision. In this review, we summarised the characteristics of the LSCN and their current and future roles in restoring corneal homeostasis in eyes with LSCD.

DRY EYE SYNDROME ASSOCIATED WITH DIABETES MELLITUS: AYURVEDIC AND MODERN VIEW

Dry eye syndrome (DES) also known as Keratoconjunctivitis sicca. Diabetes is more prone to dry eye disease and tear film dysfunctions. DM is a disease which affects both the anterior and posterior segment of the eye. DM patients more prone to Cataract, Glaucoma, Dry eye, Superficial Punctuated keratitis, recurrent corneal erosion syndrome, Persistent epithelial defects &amp; also cause microvascular complications like Neuropathy, Retinopathy. Dry eye is the disorders of the tear film due to tear deficiency or excessive evaporation which causes damage to the interpalpebral ocular surface and it is associated with symptoms of ocular discomfort. In diabetes due to poor control of DM damage to any component of lacrimal function unit leads to DES, Diabetic patients have classical symptoms of dry eye including irritation, foreign body sensation, redness, itching, burning sensation etc. In modern sciences it is treated with artificial tears drops. Frequent use of drops again leads to dryness hence alternative treatment is necessary. Ayurvedic classical text Acharya Sushruta describes Shukshkakshipaka under Sarvagata Netra Roga can be correlated with Dry eye. According to Acharya Sushruta it is Vatta vitiated disease, Acharya Vagbhata has quoted it as Vatta-pitta vitiated disease and Sharangadhara considered as Vataraktaja Vitiated disease. By analyzing different opinion of acharaya may cause dry eye by decreasing tear secretion. In Ayurveda many more treatment modalities are available for treating Shukshkakshipaka such as Snehapana, Netra Tarapana, Putapaka, Nasya, Anjana etc. This study enlightens the ayurvedic and modern review on dye eye syndrome in diabetes patient.

Autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution: a clinical comparative study

Purpose: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated. Methods: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for >6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer’s test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days. Results: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer’s test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed. Conclusions: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

Factors affecting the epithelial integrity of human donor corneas.

To evaluate various factors affecting the integrity of human donor corneal epithelium. Donor corneal buttons were evaluated for epithelial defect (ED) and exposure. The slit-lamp photographs were taken on day 01, and the data such as age and gender of the donor, cause of death, refrigeration of cadavers, death-to-preservation time (DPT), experience of technician, and distance from site of collection to eye bank were collected. A total of 100 consecutive corneal buttons belonging to 56 donors were evaluated. The median age of donors was 50 years. Males constituted 45 (80.4%). The mean DPT was 9.7 ± 5.3 hours. After death, 34 donors (60.7%) were refrigerated before the collection/retrieval. Most of the corneas (80%) were recovered by technicians having an experience of 0-5 years. Thirty-one donors (55.3%) were located at 1-50 km from the eye bank. The mean area of exposure was 15 ± 4.3 mm2. The mean area of ED was 28.7 ± 5.9 mm2. ED was significantly associated with refrigeration of cadavers and longer DPT. On multivariate analysis, only DPT was found to be significantly associated (P = 0.006; odds ratio [OR] = 1.54 ± 0.24) with the presence of ED. After transplantation, only two corneas had persistent epithelial defects and were treated successfully using various interventions. Integrity of donor corneal epithelium is mainly influenced by the refrigeration of cadavers and DPT.

Keratin films for ocular surface reconstruction: Wound healing in an in-vivo model

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.

Healing of Chemical Injury-Related Persistent Corneal Epithelial Defects With Topical Insulin.

The purpose of this study was to evaluate the effectiveness of insulin eye drops for treating refractory persistent epithelial defects (PEDs). A prospective, single-center, case series was performed from March 2020 to September 2021. All patients were prescribed insulin eye drops for refractory PEDs that failed on maximum standard medical treatment (including serum eye drops). The drops were used 4 times/day. Patients were followed up at 2 weekly intervals with full slitlamp examination and serial anterior segment photography. The primary end point was resolution of the epithelial defect. Eleven eyes of 10 patients were treated with insulin eye drops. The mean age of the cohort was 45.4 + 25 years with a mean follow-up of 195.7 + 114.3 days after re-epithelization. The most common causative condition was chemical injury (n = 5, 60%). Mean baseline PED defect was 41.3 + 55.2 mm 2 . Nine of 11 eyes (82%) fully re-epithelized within a mean time of 62.3 + 34.6 days (range 14-112). In 2 patients who did not achieve re-epithelization, one had a reduction in size from 12.25 mm 2 to 4.5 mm 2 and the other had no response. No recurrence in defect was observed in the group that had fully re-epithelized. This study showed that the use of topical insulin eye drops led to a successful resolution of PED in 9 of 11 cases. We demonstrate the use of insulin for closure of PEDs in chemical eye injury. Larger controlled studies are required to further evaluate this novel therapy.

Allogeneic Solid Platelet-Rich Plasma for Persistent Epithelial Neurotrophic Defects: A Protocol and Pilot Study

Here, we present the procedure to obtain allogeneic solid platelet-rich plasma (PRP) and its use in a pilot study of patients with persistent neurotrophic epithelial defects. We included 4 eyes of 4 patients with persistent neurotrophic epithelial defects unresponsive to other therapies from a single institution. PRP and thrombin were produced by the Department of Transfusion Medicine from healthy blood donors. PRP was activated in its solid form in the operating room with addition of thrombin and calcium gluconate 10% and applied on the cornea with fibrin glue and soft contact lens. Corneal healing time, corneal esthesiometry, visual acuity, Oxford staining score, Ocular Surface Disease Index questionnaire, and Schirmer I test were recorded. Anterior segment optical coherence tomography and in vivo confocal microscopy were also evaluated over the 4-month follow-up period. The persistent epithelial defect healed in all patients in the first 10 days. During the follow-up, there was an absence of recurrences. For all patients, there was a reduction in Ocular Surface Disease Index questionnaire score (case 1: -55 points, -73.3%; case 2: -26.3 points, -58.4%; case 3: -56 points, -69.1%; case 4: -20 points, -26.6%; mean reduction: 39.3 points, 56.85%) and Oxford staining score (case 1, 2, and 3: 3 points decrease; case 4: 2 points decrease; mean reduction: -2.75 points). Allogeneic solid PRP in combination with fibrin glue may facilitate wound healing in neurotrophic persistent epithelial defects. Further prospective studies are needed to quantify its efficacy.

Research progress on the pathogenesis of diabetes-related dry eye

In recent years, with the further understanding of medical circles on diabetic ocular complications, the ocular surface abnormalities of diabetes has drawn increasing concerns. Nearly 50% of diabetic patients suffer from dry eye symptoms. The main manifestations of diabetes related dry eye were abnormal lacrimal secretion, poor lacrimal stability, decreased corneal sensitivity, persistent corneal epithelial defect and even corneal ulcer, which were mainly related to the changes of structure and function of lacrimal gland, the decrease of goblet cells in conjunctiva, the abnormality of meibomian gland function and the degeneration of corneal nerve caused by diabetes. In this paper, we summarized and analyzed the recent research progress on the effect of diabetes on lacrimal film, corneal innervation and lacrimal gland innervation, and the correlation between oxidative stress, advanced glycation end products and diabetes-related dry eye, to explore the pathogenesis of diabetes-related dry eye and to provide reference for clinical diagnosis, treatment and research.

Comparison of Persistent Epithelial Defect Treatment With Sutureless Cryopreserved and Dehydrated Amniotic Membrane

To compare cryopreserved sutureless amniotic membrane (C-SAM) and dehydrated SAM (D-SAM) outpatient treatment outcomes for persistent epithelial defects (PEDs), analyze risk factors for treatment failure, and identify adverse events. Retrospective, interventional comparative clinical study. This study was a multicenter retrospective interventional cohort from 2 tertiary corneal referral practices from 2016 to 2020. The inclusion criteria were as follows: (1) PEDs treated (2) outpatient with (3) either C-SAM or D-SAM. PEDs were defined as epithelial defects present for ≥7 days after failing prior conservative therapy. The primary outcome measure was the resolution or improvement of a PED. The secondary outcomes included analysis of treatment failures and identification of adverse events. A total of 220 PEDs from 204 eyes (197 patients) treated with either C-SAM or D-SAM met the inclusion criteria. A total of 100 PEDs (45.5%) resolved after single amniotic membrane administration, 46.5% (59 of 127) in the C-SAM group and 44.1% (41 of 93) in the D-SAM group (P=.727). Forty-nine PEDs neither improved nor resolved without a significant difference between the C-SAM (21.3%) and D-SAM groups (23.7%, P=.673).There was no statistically significant difference for PED resolution, PED improvement, PEDs that did not resolve/improve, or those requiring surgery between the 2 groups for initial SAM. C-SAM and D-SAM were both effective for treating PEDs with comparable outcomes for resolution, improvement, and need for additional surgical intervention. Specific differences in adverse events may help dictate clinical use. Inflammatory disease was a risk factor for nonresolution of all PEDs.

Amniotic membrane (AM) for ocular surface pathology: The old and the new

AbstractThe first amniotic membrane use was dated in 1910 as a skin graft substitute material. In the ophthalmological field, it was first used in the 1940 s as a conjunctival substitute after removal of fibrotic tissue, with good results when it was contracted with rabbit peritoneum. The procedure lost interest because the tissue could only be used fresh. Clinicians regained interest in the early 1990 s when new preservation, storage and distribution methods were already available.Application methods: The way to use the amniotic membrane depends on the pathological situation for which it is indicated. The depth, shape and size of the recipient area also play a role in the therapeutic decision.In general, there are three possible situations:An inlay transplantation as a graft: The AM works as a replacement of the lost tissue because it is remodelled into the host corneal matrix over time. The amnion is placed epithelial side up, as the membrane is able to act as a substrate for epithelial regeneration.An onlay transplantation as a patch: The transplant acts as a temporary biological bandage. The AM and the molecules that produces, protect the cornea from environmental aggressions, and it also has antifibrotic effect. The amnion is placed epithelial side down. Usually the product can be removed, although it is usually self‐degraded.Combinatorial transplantation as a sandwich: Two layers are transplanted, the deepest is placed epithelial side up and the other epithelial side down, obtaining the benefits of the two techniques.The graft provides structural integrity and the patch gives protection to de the graft, while the epithelium is expected to grow between the two layers.From our point of view this is the best option.Main indications as a graft:‐Corneal ulcerations and persistent epithelial defects.‐Limbal Stem Cells Deficiency (LSCD). It can be used in Simple Limbal Epithelial Transplantation (SLET), in Amnion‐Assisted Epithelial Redirection (ACER), and as a matrix for Cultivated Stem Cell Transplantation.‐In Glaucoma, to treat leaks from blebs.‐In Neoplasias, AM is used to act as a substrate for conjunctival migration and reconstruction following excision of both malignant and benign tumours.‐In Oculoplastic surgery, AM has been suggested as a potential alternative to mucosal membrane transplantation in lid revision, orbital linings or symblepharolysis.‐In Pterygium surgery, mainly in relapsing cases in which a very large resection of the conjunctiva is made.‐In Strabismus surgery, either to cover defects or to reduce muscle fibrosis and adhesion.Main indications as a patch, for Ocular Surface Wound Healing:‐In the acute stage of Chemical/Thermal injuries.‐In the acute stage of Cicatrising Conjunctivitis (Erythema Multiforme Diseases, Pemphigoid, Graft versus Hosts Disease).‐In recurrent corneal erosions.The potential risks of amniotic transplantation will be discussed.

Adverse Reactions from Topical Ophthalmic Anesthetic Abuse.

To assess the adverse drug reactions (ADR) of tetracaine among patients referred to an eye emergency department in the southeast of Iran. In this case series study, we assessed 31 eyes of 24 patients who were referred due to adverse effects of ocular anesthetics during2017-2020. We collected the data, including age, sex, job, how the medicine was obtained, symptoms, examination results, and ADR. Of 24 patients, 22 (91.7%) were male. The mean (standard deviation) age of the patients was 32.6 (1.9) years. Twenty-two patients obtained the medicines without a prescription and a general practitioner prescribed the medicine to two patients. In the first interview, the most common symptoms were: photophobia, reduced vision, ocular pain, and redness. The main signs of persistent epithelial defect, patchy or diffuse corneal stromal infiltration, ring infiltration, and Descemet's folds were noticed in the examinations. Finally, 51.6% (n =16) of the eyes had decreased vision, 45.2% (n =14) had corneal opacity, 16.1% (n = 5) had elevated intraocular pressure that needed long-term anti-glaucoma therapy, and 6.5% (n = 2) had corneal pannus. Corneal perforation and phthisis bulbi were the final results in one eye. ADR related to the use of ophthalmic topical anesthetics could cause sight-threatening severe morbidities. It seems that some general practitioners are not careful regarding the prescription of these kinds of medicine. Moreover, the over-the-counter availability of tetracaine eye drops should be managed.

The progress in techniques for culturing human limbal epithelial stem cells.

In vitro culture of human limbal epithelial stem cells (hLESCs) is crucial to cell therapy in the treatment of limbal stem cell deficiency, a potentially vision-threatening disease that is characterized by persistent corneal epithelial defects and corneal epithelium conjunctivalization. Traditionally, hLESCs are cultivated based on either limbal tissue explants or single-cell suspensions in culture media containing xenogenous components, such as fetal bovine serum and murine 3T3 feeder cells. Plastic culture dishes and human amniotic membranes are classical growth substrates used in conventional hLESC culture systems. The past few decades have witnessed considerable progress and innovations in hLESC culture techniques to ensure a higher level of biosafety and lower immunogenicity for further cell treatment, including complete removal of xenogenous components from culture media, the application of human-derived feeder cells, and the development of novel scaffolds. Three-dimensional artificial niches and three-dimensional culture techniques have also been established to simulate the real microenvironment of limbal crypts for better cell outgrowth and proliferation. All these progresses ensure that in vitro cultured hLESCs are more adaptable to translational stem cell therapy for limbal stem cell deficiency.

Magic Bullets: The Coming Age of Meaningful Pharmacological Control of the Corneal Responses to Injury and Disease.

Corneal injuries from chemical burns, mechanical trauma, infections, immunological rejections, surgical complications, and some diseases are commonly associated with persistent epithelial defects (PED), neurotrophic epitheliopathy, scarring fibrosis, corneal neovascularization (CNV), and/or corneal endothelial damage that lead to vision loss. Several Food and Drug Administration (FDA) approved medications have recently become available, are currently in clinical trials, or are likely to enter clinical trials in the near future. For example, a 2-week course of topical human recombinant nerve growth factor is frequently an effective treatment for corneal neurotrophic epitheliopathy associated with PEDs. Topical losartan, an angiotensin converting enzyme II receptor antagonist that also inhibits TGF beta signaling, has been shown to effectively decrease myofibroblast generation and scarring fibrosis in alkali burn injury and Descemetorhexis rabbit models. Small molecule topical tyrosine kinase inhibitors, such as sunitinib and axitinib, FDA approved as chemotherapeutic agents to treat specific cancers, have also been found to be effective topical inhibitors of CNV in animal and human trials. Rho-kinase inhibitors, such as ripasudil and netarsudil, that are currently approved agents for the treatment of glaucoma in some countries, have been shown to stimulate corneal endothelial proliferation in animal studies and human trials, and may accelerate the regeneration of Descemet's membrane. These agents, as well as other drugs in development, will be used in targeted combinations to treat corneal pathophysiology associated with epithelial healing disorders, stromal scarring fibrosis, CNV, and corneal endothelial injury during the next decade.