Persistent Epithelial Defects Research Articles

BMSC-derived exosomes attenuate persistent corneal epithelial injury by affecting retinal neural-like cells

Persistent corneal epithelial defect (PED) is a challenge to human which is difficultly cured, normally requiring long-term follow-up. Herein, this study explored the potential role of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) in persistent corneal epithelial injury and the underlying mechanism. After characterization of BMSC-exos, RGC-5 cell viability was determined and surface markers of BMSCs were analyzed. Additionally, RT-qPCR and Western blot measured miR-150-5p, Brn3, Islet-1, and PCNA expression. Dual luciferase assays were conducted to evaluate the targeting relationship between long non-coding Ribonucleic Acid (lncRNA) MIAT and miR-150-5p. Presented in ellipsoidal or cup shape, BMSC-exos were positive to BMSC-specific markers CD29 and CD90, and cell surface markers CD9 and CD63 were detected on exosomes. Importantly, treatment with BMSC-exos significantly promoted proliferation of retinal ganglion cells (RGCs) and hindered cell differentiation. Interestingly, down-regulating lncRNA MIAT exerted the same effect as BMSC-exos, increasing cell viability and decreasing the expression of differentiation-related proteins Brn3 and ISL1. Bioinformatics software predicted miR-150-5P as target of lncRNA MIAT, and the relative luciferase activity of miR-150-5P+MIAT-WT co-transfection group was lower. Conclusively, BMSC-exos can improve PED by targeting and regulating miR-150-5p expression through lncRNA MIAT, which can up-regulate PCNA in RGC-5 cells and down-regulate Brn3 and ISL1.

Decellularized Descemet Membrane Anterior Keratoplasty With Allogeneic Simple Limbal Epithelial Transplantation for Partial Limbal Stem Cell Deficiency Following Partial Keratolimbal Allograft Failure.

The purpose of this study was to describe the use of Descemet membrane anterior keratoplasty (DMAK) with modified allogeneic simple limbal epithelial transplantation to treat a case of partial limbal stem cell deficiency (LSCD) following keratolimbal allograft failure. Case report. A 21-year-old woman with autoimmune polyglandular syndrome-related LSCD presented with pain and decreased vision. There was partial failure and recurrence of LSCD after a severe/acute keratolimbal allograft rejection that led to persistent epithelial defects refractory to conservative therapy. This was treated with a superficial keratectomy and placement of a DMAK. A modified allogeneic simple limbal epithelial transplantation was performed with an overlying amniotic membrane and temporary tarsorrhaphy. There was epithelialization of the corneal surface by 3 to 4 weeks with an improved ocular surface. Despite partial recurrence of late staining, the cornea has remained epithelized, vision has improved, and the patient has remained pain-free more than 1.5 years following the procedure. DMAK may be a long-term substrate to help improve and maintain epithelization of the cornea up to 1.5 years. DMAK may be a viable alternative to using amniotic membrane as a scaffold in allogeneic simple limbal epithelial transplantation for treatment of partial LSCD. While late epithelial staining recurred in our patient, DMAK appears to prevent recurrent epithelial defects and reduce ocular surface pain, conveying an improvement in quality of life in patients at high risk of rejection/failure.

Management of Ocular Surface Inflammation with Persistent Epithelial Defects Using a Sutureless Human Amniotic Membrane Dehydrated Matrix: A Prospective Study Utilizing a Digital Ocular Surface Assessment Tool

Management of Ocular Surface Inflammation with Persistent Epithelial Defects Using a Sutureless Human Amniotic Membrane Dehydrated Matrix: A Prospective Study Utilizing a Digital Ocular Surface Assessment Tool

Topical Insulin Eye Drops: Stability and Safety of Two Compounded Formulations for Treating Persistent Corneal Epithelial Defects.

Compounded insulin eye drops were prepared at 1 IU/mL from commercially available subcutaneous insulin by dilution in saline solution or artificial tears. Physicochemical characterization and in vitro tolerance testing in human and conjunctival cells were followed by a 28-day short-term stability study under various conditions. The formulations were isotonic (280-300 mOsm/L), had a pH close to neutral (7-8), medium surface-tension values (<56 MN/m-1), and low (≈1 mPa·s) and medium (≈5 mPa·s) viscosities (compounded normal saline solution and artificial tear-based preparation, respectively). These values remained stable for 28 days under refrigeration. Microbiological stability was also excellent. Insulin potency remained in the 90-110% range in the compounded formulations containing normal saline solution when stored at 2-8 °C for 28 days, while it decreased in those based on artificial tears. Although both formulations were well tolerated in vitro, the compounded insulin diluted in a normal saline solution exhibited better cell tolerance. Preliminary data in humans showed that insulin in saline solution was an effective and safe treatment for persistent corneal epithelial defects. Compounded insulin eye drops diluted in normal saline solution could, therefore, constitute an emergent therapy for the treatment of persistent corneal epithelial defects.

Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology

To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. Proprietary or commercial disclosure may be found after the references.

Corneal Epithelial Changes in Diabetic Patients: A Review.

The relationship between diabetes mellitus and ocular complications has been extensively studied by many authors. Diabetic keratopathy has already been well characterized and defined as a clinical entity. This review focuses on exploring corneal epithelial changes in diabetic patients, aiming to provide a pragmatic overview of the existing knowledge on this topic. The paper systematically examines alterations in corneal epithelial structure and their impact on diabetic patients. Advanced imaging techniques are also discussed for their role in precise characterization and improved diagnostics. Additionally, the paper explores the mechanisms behind corneal epithelial changes in diabetes, looking at factors such as hyperglycemia, oxidative stress, and Advanced Glycation End-Products. The impact of altered corneal epithelial integrity on barrier function and susceptibility to external issues is considered, addressing potential links to heightened proteolytic enzyme activities and delayed wound healing observed in diabetic individuals. The review also covers the practical implications of corneal epithelial changes, including the association with corneal erosions, persistent epithelial defects, and an increased risk of dry eye syndrome in diabetic patients.

EFFECTIVENESS AND SAFETY OF AMNIOTIC MEMBRANE GRAFTING FOR CORNEAL SURFACE DISORDER: A RANDOMIZED CLINICAL STUDY

Objective: The aim of the study was to evaluate the effectiveness and safety of freeze-dried amniotic membrane grafting (AMG) and compare it against traditional medical therapy for the management of corneal surface disorders. Methods: A randomized clinical trial was conducted on 60 patients with corneal surface disorders who were randomized equally either into the AMG group (n=30) or medical management group (n=30). Patients in both groups were followed up for 8 weeks after receiving group-specified intervention or till complete resolution (whichever was earlier). Treatment outcome, healing time, improved vision, decreased pain, recurrence rate, and corneal clarity were the main outcome metrics. Results: The most common corneal disorder was persistent epithelial defect (38.33%), closely followed by impending perforated corneal ulcer (31.66%). Majority of the patients (36.66%) had corneal involvement of &gt;75%, while 31.66% had involvement ranging from 50 to 75%. The success rate of AMG (96.7%) was significantly higher than that of medical management (76.7%) in the treatment of corneal surface disorders (p=0.022). During the follow-up period, the incidence of allergic reactions was slightly lower in the AMG group (6.7%) compared to the medical management group (10.0%). Overall, the incidence of side effects and other complications was low in both the AMG group and the medical management group. The severity of side effects was comparable in both the study groups (p=0.886). The recurrence rate of corneal surface disorders in the in the AMG group (6.7%) was statistically lower than that in the medical management group (26.7%) (p=0.037). Conclusion: The findings of the present study supported the use of AMG as an effective and safe alternative to medical management for the treatment of conditions affecting the corneal surface.

Topical Insulin Treatment for Neurotrophic Corneal Ulcer with Persistent Epithelial Defect

Background: Neurotrophic keratitis (NK) is a degenerative corneal disease caused by impairment of corneal sensory innervation. It is characterized by decreased or absent corneal sensation, leading to epithelial breakdown, impairment of healing, and ultimately to the development of corneal ulceration, melting, and perforation. We described a case of neurotrophic ulcer with persistent epithelial defect and its remarkable healing response to insulin eye drop treatment. Case Presentation: A 62-year-old male patient was referred to our hospital for the management of stage III NK in the left eye. The condition started 6 months ago; the patient developed a sudden onset of left eye diminution of vision, red eye, and tearing. The patient sought an ophthalmic consultation and was diagnosed with herpes simplex keratitis. On examination, visual acuity OS was hand motion (HM), severe conjunctival injection, deep corneal vascularization, corneal opacity with stromal infiltration, epithelial defect about 3.5 x 6 mm, stromal thinning, Descemet membrane folds and loss of corneal sensation by cotton wisp test. The patient was treated with topical insulin eye drops for 6 weeks and showed substantial ulcer healing and reepithelization of the epithelial defect. Conclusion: Insulin drops have been shown to substantially promote persistent epithelial defect healing in the case of neurotrophic ulcers. Therefore, topical insulin use can potentially help in the treatment of refractory neurotrophic keratitis. Further studies with large case numbers and long follow-ups should be the main focus of future research.

Clinical Outcomes and Indications of In-Office Sutureless Dried Gamma Ray-Sterilized Human Amniotic Membrane Transplantation With Bandage Contact Lenses in Various Ocular Surface Disorders.

The purpose of this study was to investigate the efficacy and indications of using dried gamma ray-sterilized amniotic membrane (AM) transplantation with bandage contact lenses for the in-office sutureless treatment of various ocular surface diseases. This study retrospectively included 56 eyes of 52 patients with various ocular surface diseases treated with sutureless dehydrated AM-assisted therapeutic contact lenses. The patients were followed up and assessed 1, 2, and 4 weeks after the treatment, and the therapeutic contact lenses were removed after 1 or 2 weeks. The size of the corneal lesion and the degree of pain experienced by each patient before and after the procedure were measured. Corneal re-epithelization rate and clinical aspects related to re-epithelialization were evaluated. Complete corneal re-epithelialization of the epithelial defect was observed in 40 eyes. The complete re-epithelialization rates of persistent epithelial defect caused by infectious ulcers, neurotrophic ulcers, ulcers due to burn, toxic keratopathy, previous penetrating keratoplasty or other corneal surgeries, and severe dry eye disease were 69.2%, 80.0%, 77.8%, 100%, 75.0%, and 100%, respectively. Five patients with uncontrolled infectious ulcers, neurotrophic ulcer, bullous keratopathy, and ulcers associated with rheumatic disease did not show significant improvement. Patient pain scores significantly decreased after the procedure. Dehydrated AM transplantation with a bandage contact lens is minimally invasive and easily applicable through in-office procedures. This approach is expected to be more actively applied in various ocular surface disorders, not only in severe corneal diseases but also in relatively mild corneal surface diseases.

Amnion Membrane Transplantation: A Therapy for Persistent Epithelial Defect as A Result of Neurotrophic Keratitis

Introduction : A persistent epithelial defect (PED) is a failure of re-epithelialization and complete healing of the cornea. The primary goal of PED treatment is to create a favorable environment for corneal wound healing. Amniotic membrane transplants (AMT) become one of the refractory cases treated for PED. This study aims to report AMT as therapy for a PED.&#x0D; Case Illustration : A fifty-six-year-old male presents with a chief complaint of redness and pain in the left eye in the last2 weeks. The patient complained of blurred vision, tearing, and foreign body sensations. An ophthalmology examination of the left eye revealed that it was close to face finger counting in visual acuity and had a persistent epithelial defect, corneal edema, descemet fold, and a decrease in corneal sensation. The patient was diagnosed with PED and received autologous serum eye drops, levofloxacin eye drops, vitamin A palmitate eye gel, and acyclovir 400mg twice a day, but did not respond adequately. AMT was planned for the patient. The patient's pain level improved one week after surgery.&#x0D; Discussion : The most common symptom of PED is pain. There are various etiological factors for PED. Neurotropic keratitis has emerged as one of the causes of PED. Management for PED is carried out sequentially according to the protocol.&#x0D; Conclusion : Amniotic membrane transplantation has become an alternative therapy for PED. The amniotic membrane provides re-epithelialization of the cornea and anti-inflammatory properties. The prognosis for AMT as a therapy for PED is quite good.

Management Strategies of Ocular Alkaline Chemical Injury

Introduction : Ocular chemical burns are true ophthalmic emergencies that can cause permanent corneal and intraocular damage leading to visual impairment or even blindness. When a case of chemical trauma occurs, immediate and appropriate management should be done.&#x0D; Case Illustration : A 24-year-old man came to Cicendo Eye Hospital with complaints of blurry eyes accompanied by burning and watery eyes after being doused with a bucket of cement mortar two weeks earlier. Ophthalmologic examination obtained visual acuity for the right eye 1/300 and left eye was 1/60. The anterior segment of both eyes showed corneal edema, conjunctivalization, persistent epithelial defects, limbal ischemia, and punctate epithelial erosion. There was an ulcer and thinning of the corneal layer in left eye. He was diagnosed with alkaline chemical injury Dua's classification grade VI on the right eye and grade V on the left eye (Figure 1). The patient then underwent a keratectomy, conjunctival resection, and amniotic membrane transplantation procedure. On the seventh day postoperatively, symptoms and clinical features improved with the visual acuity of both eyes improved to 1/60 (Figure 2).&#x0D; Discussion : Amniotic membrane graft was performed in late reparative phase which aims to preserve the surface of the corneal epithelium and prevent corneal perforation and inflammation. Conjunctival resection was performed to prevent neovascularization of the amniotic membrane.&#x0D; Conclusion : Management of ocular burn injury requires an immediate and comprehensive treatment to achieve good result. In this case successful treatment was achieved by improvement of visual acuity and no complication occured.

Management Strategies of Ocular Alkaline Chemical Injury

Introduction : Ocular chemical burns are true ophthalmic emergencies that can cause permanent corneal and intraocular damage leading to visual impairment or even blindness. When a case of chemical trauma occurs, immediate and appropriate management should be done.&#x0D; Case Illustration : A 24-year-old man came to Cicendo Eye Hospital with complaints of blurry eyes accompanied by burning and watery eyes after being doused with a bucket of cement mortar two weeks earlier. Ophthalmologic examination obtained visual acuity for the right eye 1/300 and left eye was 1/60. The anterior segment of both eyes showed corneal edema, conjunctivalization, persistent epithelial defects, limbal ischemia, and punctate epithelial erosion. There was an ulcer and thinning of the corneal layer in left eye. He was diagnosed with alkaline chemical injury Dua's classification grade VI on the right eye and grade V on the left eye (Figure 1). The patient then underwent a keratectomy, conjunctival resection, and amniotic membrane transplantation procedure. On the seventh day postoperatively, symptoms and clinical features improved with the visual acuity of both eyes improved to 1/60 (Figure 2).&#x0D; Discussion : Amniotic membrane graft was performed in late reparative phase which aims to preserve the surface of the corneal epithelium and prevent corneal perforation and inflammation. Conjunctival resection was performed to prevent neovascularization of the amniotic membrane.&#x0D; Conclusion : Management of ocular burn injury requires an immediate and comprehensive treatment to achieve good result. In this case successful treatment was achieved by improvement of visual acuity and no complication occured.

Pseudopterygium After Limbal Dermoid Cyst Excision in a Child with Goldenhar Syndrome

Introduction : Goldenhar syndrome is a rare congenital disorder also known as oculoauricularvertebral dysplasia. Limbal dermoid associated with this syndrome. This case report aims to present an reccurent pseudopterygium after three times limbal dermoid cyst excision in patient with Goldenhar syndrome.&#x0D; Case Illustration : Patient 13 years old male with pseudopterygium in right eye. Visual acuity both eyes 6/6 snellen chart. Fibrovascular tissue from tarsal conjunctival inferotemporal to 2 mm limbal cornea in right eye. Patient had limbal dermoid cyst in right eye since birth and underwent limbal dermoid cyst excision for three times. First time surgery used amniotic membrane transplantation, then second and third surgery used conjunctival limbal graft. Goldenhar syndrome have been diagnosed since the age of 2 years old. External examination noticed asymmetrical hemifacial microsmia, grade III microtia right ear, conduction deafness, and laryngomalacia.&#x0D; Discussion : Limbal dermoid cyst is one of characteristic of Goldenhar syndrome. In this case pseudopterygium grade II in right eye developed after limbal dermoid cyst excision for three times. Limbal dermoid simple excision may lead to corneal vascularization persistent epithelial defect, scar, and pseudopterygium. Various surgical include superficial keratectomy, amniotic membrane transplantation and lamellar or penetrating keratoplasty. Pseudopterygium still occurs in this case, even though recurrence has been prevented by administration of amniotic membrane transplantation and conjunctival limbal graft.&#x0D; Conclusion : We should be concerned about management of limbal dermoid cyst with Goldenhar syndrome to prevent recurrent pseudopterygium.

Prevention and Treatment of Persistent Epithelial Defects After Common Refractive Surgery Procedures.

To discuss the prevention and treatment of persistent epithelial defects after the most common refractive surgeries-photorefractive keratectomy, laser in situ keratomileusis, or small incision lenticule extraction. PubMed was used to search the medical literature. Persistent epithelial defects are infrequent after photorefractive keratectomy, laser in situ keratomileusis, or small incision lenticule extraction. In the authors' opinion, any persistent epithelial defect present at 1 week or beyond after surgery should be treated aggressively with a properly fit bandage contact lens, lubrication with non-preserved artificial tears, and treatment of any eyelid abnormalities, including nocturnal lagophthalmos. Consideration should be given for presumptive treatment for herpes simplex virus or varicella zoster virus infection. If the persistent epithelial defect does not close within 2 weeks, then other measures should be considered, such as autologous serum drops, topical losartan, amniotic membranes, and topical human recombinant nerve growth factor to limit corneal scarring fibrosis and microbial infection. Persistent epithelial defects are among the most feared complications of refractive surgery. Timely and aggressive treatment should be instituted to close the epithelium prior to the development of scarring fibrosis and/or microbial corneal infection. [J Refract Surg. 2024;40(2):e117-e124.].

Persistent epithelial defects in neurotrophic keratopathy

One of the complications of neurotrophic keratopathy is the breakdown of the corneal epithelium. This can progress to non‐healing persistent epithelial defects (PED) which are challenging to manage and can lead to corneal ulceration, scarring and perforation.The causes of epithelial breakdown, prevention and contemporary medical and surgical management will be discussed during this talk. The use of conservative methods available to all clinical settings all they way to more sophisticated surgical methods available in tertiary referral centres, will be presented and discussed.

Contact lens‐related complications

The use of contact lens is very popular and its global market is growing. They have numerous applications, some well‐established and others still not consensual but which have been gaining more and more approval, namely refractive errors, dry eye management, post refractive surgery rehabilitation, persistent epithelial defects, cosmetic approaches and drug delivery systems. Unfortunately, there are some complications caused by their use, some of them sight threatening. The purpose of this presentation is to review these problems and to provide a better understanding of them.The major mechanisms implicated are numerous: trauma, decreased corneal oxygenation, reduced corneal and conjunctival lubrication, allergic and inflammatory responses and infection. However, depending on the complication we are talking about, there are other factors involved, such as contact lens‐related factors (material, design, fit and wearing schedule) and environmental factors (ocular surface condition, external environment, occupational factors, medications and compliance).The symptomatology experienced by patients ranges from hypoesthesia and mild conjunctival hyperemia to photophobia, contact lens intolerance and even decreased visual acuity.Many complications have been described. The most important (most common or most serious) are contact lens discomfort (CLD), dry eye, corneal deepithelialization (CD), sterile infiltrates (SI), corneal neovascularization (CNV), infectious keratitis (IK) and giant papillary conjunctivitis (GPC). Superior epithelial arcuate lesion, contact lens‐related peripheral ulcer, corneal distortion, hypoesthesia, ptosis, pinguecula, corneal edema, allergy aggravation, herpes reactivation and endothelial changes have also been described.CLD is an episodic or persistent adverse ocular sensation related to lens wear with a variable incidence in the literature, ranging from 23% to 94% in different series, being less common with soft lenses. Dry eye plays its role acting as a risk factor for CLD and/or as a consequence of contact lens use. CD manifests as punctate epithelial keratopathy, epithelial abrasions, foreign body tracks, corneal dellen, microcysts, vacuoles, mucin balls and dimple veiling. GPC is one of the most common adverse effects of contact lenses and the papillary reaction of the upper tarsal conjunctiva is the main feature of this entity. CNV is the formation of new vessels basically found in capillaries and venules of the pericorneal plexus, which may progress to the corneal stroma. They are much more associated with soft contact lenses, especially in extended wearers. Of note, contact lens use is one of the most common causes of CNV usually highlighted. SI are the result of an immunological reaction, often do not contain overlying epithelial defect or anterior chamber reaction and may manifest as stromal deep opacities. IK may be caused by bacteria, viruses, fungus or parasites and prompt immediate care and close revaluations to anticipate disastrous outcomes.Conservative measures play a role in almost all complications and their prevention, such as patient education, lubrication, contact lens exchange when applicable and modification of environmental factors. Addressing and learning how to prevent or quickly diagnose all these complications is crucial to prevent serious consequences.

Modern techniques and features of selective keratoplasty

Selective keratoplasty involves replacing the affected layers of the cornea with similar donor tissue. In case of pathological changes in the middle and posterior stroma, deep anterior lamellar keratoplasty (DALK) is performed. Chronic corneal edema caused by endothelial dysfunction is an indication for endothelial keratoplasty - Descemet membrane endothelial keratoplasty (DMEK) or Descemet Stripping Endothelial Keratoplasty (DSAEK). Compared to penetrating keratoplasty (PK), these operations are characterized by a low risk of damage to intraocular structures and a relatively short rehabilitation period. Complications of selective keratoplasty include the formation of a false chamber between the lamellar graft and the recipient's cornea, ocular hypertension during anterior chamber air tamponade. Persistent epithelial defect can be a sign of primary graft failure in DALK, DSAEK and DMEK. Selective keratoplasty is characterized by a lower incidence of immune rejection than PK. In some cases, DALK can be complicated by corneal changes related to suture fixation of the graft. Long-term postoperative use of topical glucocorticoids can cause ocular hypertension and cataracts.

Blood‐derived trophic factors for the treatment of ocular surface diseases

The use of blood‐derived products (Eye Drop of Human Origin—EDHO; in Italian: Emocomponents for Not Transfusional Use, EUNT) for the treatment of various ocular surface diseases has become increasingly utilized in ophthalmic practice over the years. In particular, they are recommended as a third line option, when conventional tear substitutes, or active drugs, such as corticosteroids or Cyclosporine A, result unsuccessful in controlling either signs and, perhaps most importantly, subjective symptoms of discomfort and pain. The rationale for their use is based on the stimulation of cell proliferation and migration through the supply of metabolically active substances, in particular growth factors, and definitely mimicking the function of natural tears.EDHO have been used for the treatment of various ocular surface diseases, including dry eye, persistent corneal epithelial defect, corneal ulcer, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion and limbal stem cell deficiency. However, the therapeutic potential of these products is still to be fully explored, as randomized clinical trials and internationally recognized harmonized guidelines are still needed to provide better evidence, improve quality of the final products and lead to a more widespread use of these therapies in daily clinical practice. The autologous source is still quite popular, although allogeneic sources appear to be a promising innovation. These might offer the solution of obtaining in advance products tailored for each patient and ocular surface disease, at scalable concentrations based on the severity of the disease and clinical parameters. There remain many unanswered questions regarding what might be considered optimal treatment, sketched as “The 5 Ws (and 2 H) for blood based eye drops”, to quote a review from our group (doi: 10.3390/jcm8091478). This presentation will discuss: 1. who is the patient to be treated, in terms of disease type, severity, and stage?; 2. Why is an EDHO needed, in terms of a target indication?; 3. When is it appropriate to prescribe an EDHO therapy?; 4. Where are EDHO be dispensed, and is a national/regional program a feasible solution to optimize resources?; 5. What is the EDHO of choice, which source and preparation are targeted for a given patient? And further: 1. how is EDHO standardized in terms of processing to ensure an optimal dilution, solvent, dispenser, storage time?; 2. How is EDHO delivered to the ocular surface, in terms of form, dose‐size modulation, length of treatment?An interdisciplinary work with transfusional medicine specialists is imperative to share information and competences, to achieve a better clinical management.

A New Treatment for Recalcitrant Neurotrophic Keratopathy of Ocular Graft-Versus-Host Disease with Virus Infection.

Neurotrophic keratopathy (NK) is a rare degenerative ocular disease that can be difficult to treat. There were no effective resolutive treatments for severe NK caused by ocular graft-versus-host disease (oGVHD) along with virus infection. To address this question, we designed a prospective cohort study to evaluate the efficacy and safety of topical recombinant human nerve growth factor (rhNGF) in patients with recalcitrant NK of oGVHD and viral infection. This prospective cohort study enrolled patients with recalcitrant NK diagnosed with oGVHD and treated with rhNGF. Clinical evaluations included the range of epithelial defects, best corrected visual acuity, intraocular pressure, slit-lamp examination, and corneal fluorescein staining. Examinations of the central corneal thickness, corneal sensitivity, and nerve fiber regeneration were performed at each visit at 4, 8, 12, 20weeks and 6months, respectively, after initiating rhNGF treatment. All enrolled patients were diagnosed with NK at stage2 (7 eyes, 63.6%) or stage3 (4 eyes, 36.4%) and responded to rhNGF treatment. Five of 11 (45.5%) and 9 of 11 eyes (81.8%) achieved complete corneal epithelial healing after 4 and 8weeks, respectively. All 11 eyes (100%) achieved complete corneal healing after 12weeks. There was also a significant reduction in the corneal ulcer area during each visit (P < 0.001), as well as in the corneal fluorescein staining score (P < 0.010). There was a significant improvement in corneal sensation when compared to the baseline (P < 0.050). Topical treatment with rhNGF effectively promoted the complete corneal healing of persistent epithelial defects and corneal ulcers in patients with recalcitrant NK in oGVHD and viral infection.

Corneal Superficial Plaque Formation After Recombinant Human Nerve Growth Factor Use in a Patient With Neurotrophic Keratopathy and Limbal Stem Cell Deficiency From Mucous Membrane Pemphigoid.

The aim of this study was to report a rare observation of corneal superficial plaque formation after topical recombinant human nerve growth factor (rhNGF) treatment for a nonhealing epithelial defect in a patient with advanced mucous membrane pemphigoid, limbal stem cell deficiency, and neurotrophic keratopathy. This study was a case report. A 72-year-old man with a complex course of mucous membrane pemphigoid, leading to cicatrizing keratoconjunctivits, limbal stem cell deficiency, and neurotrophic keratopathy presented with a recurrent persistent epithelial defect in the right eye. After a long course of unsuccessful epithelial healing, despite various treatment modalities, he was administered topical rhNGF (cenegermin 0.002%; Oxervate, Dompé US Inc., Boston, MA) which successfully resolved the epithelial defect. However, on day 22 posttreatment, an unusual white, thick, adherent corneal superficial plaque formed. rhNGF was stopped and the plaque was carefully removed. Subsequently, there was no recurrence, and the patient's epithelial healing remained stable. Although the successful resolution of the persistent epithelial defect with rhNGF administration was notable, the development of the unusual epithelial overgrowth emphasizes the importance of vigilant monitoring and evaluation when using rhNGF in complex ocular conditions. Making informed decisions on the timing of discontinuing rhNGF can lead to desirable effects of the drug while mitigating additional side effects when managing such challenging cases.