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Corneal epithelial defects are one of the most common ocular disorders. Restoring corneal integrity is crucial to reduce pain and regain function, but in cases of neurotrophic or desensitized corneas, healing can be significantly delayed. Treating neurotrophic corneas is challenging for ophthalmologists, and surgical intervention is often indicated to manage refractory cases that are unresponsive to medical therapy. Over the last decade, as more expensive therapeutics reach the market, topical insulin has returned to the forefront as an affordable option to improve corneal wound healing. There is still a paucity of data on the use and the efficacy of topical insulin, with no consensus regarding its indications, preparation, or posology. Here we review the literature on topical insulin for corneal and ocular surface pathologies, with a focus on the current evidence, its mechanisms of action, and its safety profile. Additionally, we share our experience in the field and provide a potential framework for future research. [ABSTRACT FROM AUTHOR]

Purpose: To report the clinical outcomes achieved in refractory cases of neurotrophic keratopathy (NK) through the utilization of insulin eye drops alone or in conjunction with a drug-depository contact lens (DDCL). Observations: This multicentric prospective open-label uncontrolled case series included consecutive patients with NK refractory to conventional treatment. Insulin eye drops (1 unit/mL) were prescribed 4 times/day in all cases, and a Therapeutic Hyper-CL™ soft contact lens (EyeYon Medical, Ness Ziona, Israel), designed to act as a drug reservoir, was applied in selected patients. Data about stage and duration of NK, corneal sensitivity, previous treatments, rate and speed of healing, changes of NK area over time were collected. Nine eyes of 8 patients (mean age 52.50 ± 12.03 years [95 % CI, 44.13–60.87]) affected by NK refractory to conventional medical therapy were included. All patients received topical insulin, while DDCL was also applied in 3 cases. At T0, the mean area of the corneal epithelial defect was 21.84 ± 18.35 mm2 [95 % CI, 9.86–33.84]. Complete corneal re-epithelialization occurred in all cases, after a mean time interval of 25.78 ± 8.39 days [95 % CI, 20.30–31.26]. Mean reduction rate of epithelial defect areas was −0.81 ± 0.44 mm2/day [95 % CI, −1.16 to −0.46] for patients treated with insulin eye drops, and −0.63 ± 0.30 mm2/day [95 % CI, −0.96 to −0.29] for those treated with insulin eye drops plus DDCL (p = 0.71). Neither adverse events nor episodes of NK recurrence were reported. Conclusions and importance: Topical insulin, used alone or in combination with DDCL, is an accessible, inexpensive, and effective treatment for refractory NK.

Abstract The aim was clinical evaluation of the efficacy of topical insulin eye drops in patients with refractory persistent epithelial defects (PEDs). This prospective non-randomized investigation was conducted to examine the efficacy of insulin eye drops in treating patients with PEDs that did not respond to conventional therapy. A total of twenty-three patients were included in the study, and they were administered insulin eye drops formulated as 1 U/mL, four times a day. The rate of epithelial defect resolution and time to complete corneal re-epithelialization were considered primary outcome measures. The relative prognostic impact of initial wound size and other parameters, including age, sex, smoking, diabetes, and hypertension were also analyzed. The results showed that during follow-up (maximum 50 days), a total of 16 patients (69.6%) achieved improvement. Insulin eye drops significantly reduced the corneal wounding area in 75% of patients with small epithelial defects (5.5 mm2 or less) during 20 days. Only 61% of patients with moderate epithelial defects (5.51–16 mm2) showed a significant recovery in 20–30 days. Also, 71% of patients with a defect size greater than 16 mm2, demonstrated a significant improvement in the rate of corneal epithelial wound healing in about 50 days. In conclusion topical insulin reduces the PED area and accelerates the ocular surface epithelium wound healing.

Sundas Ejaz Maqsood,1,2 Samer Hamada,1 Damian Lake,1 Artemis Matsou,1 Mohamed Elalfy1– 3 1Corneao- Plastic Unit, Queen Victoria Hospital, East Grinsted, West Sussex, UK; 2Cornea Service, Ophthalmology, Maidstone and Tunbridge Wells NHS Trust, Kent, UK; 3Cornea Department, Research Institute of Ophthalmology, Giza, EgyptCorrespondence: Mohamed Elalfy, Ophthalmology Department, Maidstone and Tunbridge Wells NHS Trust, Hermitage Lane, Maidstone, Kent, ME16 9QQ, UK, Email Mohamed.elalfy@nhs.netPurpose: To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a digital ocular surface disease assessment tool.Methods: Two UK NHS Trusts — Queen Victoria Hospital Foundation Trust (East Grinstead and Maidstone) and Tunbridge Wells Trust (Kent) — prospectively treated patients with ocular surface disease with sutureless HAMDM. The patient cohort was assessed for resolution of epithelial defects, ocular surface inflammation, and best-corrected visual acuity pre- and posttreatment. Measurements of ocular surface inflammation and epithelial defect size were assessed using AOS digital imaging software, a validated tool for objective grading of bulbar conjunctival redness and measurement of corneal epithelial defects.Results: A total of 47 applications of sutureless HAMDM on 46 eyes of 46 patients (25 male, 21 female, age 9– 94 years) were assessed across various etiologies for an average of 24.0± 14.1 days. Patients with limbal stem-cell deficiency (n=17), persistent epithelial defects (n=16), neurotrophic corneal disease (n=7), filamentary keratitis (n=2), corneal erosion (n=1), corneal thinning (n=1), ocular surface inflammation (n=1), and traumatic corneal laceration (n=1) were included in the study. Across all patents, 63% of eyes showed complete healing of epithelial defects and 32.6% of eyes showed partial resolution. The average rate of healing (wound closure) was 0.36 mm2 per day across the overall patient cohort, and the rate of healing in cases with complete resolution of epithelial defects was 0.41 mm2 per day. Inflammation across all four quadrants of the ocular surface remained stable. Visual acuity across the patient cohort remained stable (61%) and improved in 26% of patients (0.06± 0.51 logMAR).Conclusion: Sutureless HAMDM application can be accomplished in just a few minutes and effectively treat a range of ocular surface disease in a clinical, nonsurgical setting. The AOS imaging software offered a quantitative methodology for measuring epithelial defect size and inflammation state.Keywords: dehydrated human amniotic membrane, sutureless, ocular surface inflammation, persistent epithelial defect, digital imaging

The aim was clinical evaluation of the efficacy of topical insulin eye drops in patients with refractory persistent epithelial defects (PEDs). This prospective non-randomized investigation was conducted to examine the efficacy of insulin eye drops in treating patients with PEDs that did not respond to conventional therapy. A total of twenty-three patients were included in the study, and they were administered insulin eye drops formulated as 1 U/mL, four times a day. The rate of epithelial defect resolution and time to complete corneal re-epithelialization were considered primary outcome measures. The relative prognostic impact of initial wound size and other parameters, including age, sex, smoking, diabetes, and hypertension were also analyzed. The results showed that during follow-up (maximum 50 days), a total of 16 patients (69.6%) achieved improvement. Insulin eye drops significantly reduced the corneal wounding area in 75% of patients with small epithelial defects (5.5 mm2 or less) during 20 days. Only 61% of patients with moderate epithelial defects (5.51–16 mm2) showed a significant recovery in 20–30 days. Also, 71% of patients with a defect size greater than 16 mm2, demonstrated a significant improvement in the rate of corneal epithelial wound healing in about 50 days. In conclusion topical insulin reduces the PED area and accelerates the ocular surface epithelium wound healing. [ABSTRACT FROM AUTHOR]

A persistent epithelial defect (PED) is a corneal epithelial defect that failed to heal after 2 weeks. It is a condition that carries much morbidity, and our understanding of PED remains poor, with current treatment methods often having unsatisfactory outcomes. With PEDs becoming more prevalent, more efforts are required to establish reliable treatment modalities. Our reviews describe the causes of PEDs and the different approaches developed to manage them, as well as their associated limitations. Emphasis is placed on understanding various advances in the development of new treatment modalities. We have also described a case of a woman with a background of graft-versus-host disease on long-term topical corticosteroids who developed complicated PED involving both eyes. The current approach to managing PEDs generally involves exclusion of an active infection, followed by treatment modalities that aim to encourage corneal epithelial healing. Success rates, however, remain far from desirable, as treatment remains challenging due to multiple underlying etiologies. In summary, advances in the development of new therapies may be able to facilitate progress in the understanding and treatment of PED. [ABSTRACT FROM AUTHOR]

Purpose: To describe the long-term outcome of the use of a specialized scleral lens known as a prosthetic replacement of the ocular surface ecosystem (PROSE) device to support the ocular surface in patients with a Boston Keratoprosthesis (KPro) Type I. All patients in this series were unable to pursue continuous wear of a bandage soft contact lens (BSCL) – a critical aspect of post KPro implantation management intended to protect the corneal carrier tissue from desiccation and stromal melting. Observations: Four eyes of four patients with a Boston KPro Type I were included. All four had failed BSCL wear and were instead treated with PROSE device wear. All four patients had underlying diagnoses associated with a diseased ocular surface (Stevens-Johnson Syndrome [one patient], prior failed penetrating keratoplasty associated with herpes zoster-related neurotrophic keratopathy [one patient], and prior failed penetrating keratoplasty associated with severe dry eye disease [two patients]). Causes of failure of BSCL wear included poor retention, discomfort, and poor vision. PROSE device wear was initiated on average seven and a half (range four to 14) months post-KPro implantation. The wear schedule varied and ranged from waking-hour wear only to 24-h wear. The average duration of device wear was 59.3 (range 28–103) months. Two patients exhibited persistent corneal epithelial defect formation with waking-hour wear, which resolved within 10 days with 24-h device wear. All patients exhibited improvement in vision with PROSE compared to baseline, averaging six and a half (range six to eight) lines of improvement in Snellen acuity, and all patients reported increased comfort. There was no incidence of microbial keratitis, KPro device instability, or other complication throughout the duration of device wear. Conclusions and Importance: This report offers a novel alternate approach to long-term support of the ocular surface in patients with a Boston KPro who fail standard continuous BSCL wear.

To study the efficacy of 100% Leptospermum medical grade Manuka honey ointment in persistent corneal epithelial defects (CEDs). Case series. Case 1 was a 25-year-old female patient who presented to the cornea clinic with a persistent CED (3.5 mm), following acanthamoeba keratitis, that had failed to respond to heavy, frequent lubrication drops and ointment. Two weeks later, after starting Leptospermum honey ointment (4 times per day), the CED healed totally. Case 2 was a 48-year diabatic, single-eyed female patient who presented with a persistent CED (1.5 × 1.5 mm) that had failed to respond to heavy, frequent lubrication drops and ointment. The CED healed three weeks after starting Leptospermum honey ointment (4 times per day). Leptospermum honey ointment can be a potential treatment for persistent epithelial defect. [ABSTRACT FROM AUTHOR]

Autologous serum eye drops provide lubrication and promote epithelial healing. They have been successfully used in the management of ocular surface disorders such as dry eye disease, persistent epithelial defects and neurotrophic keratopathy for many decades. A great deal of variation in the methods of preparation of autologous serum eye drops, the end concentration and the duration of use exists in published literature. In this review, simplified recommendations for preparation, transport, storage and use of autologous serum are described. Evidence for the use of this modality in aqueous deficient dry eye disease is summarized, along with expertise-based rationale.

This case report aims to describe a modified continuous suturing technique for firm fixation of a human amniotic membrane graft in a patient with persistent epithelial defect (PED) after a chemical eye injury. As a result of this technique, the amniotic membrane (AM) was firmly fixed to the corneal surface with eight continuous and locked episcleral sutures that resembled an octagon graft. This technique was performed in a 14-year-old patient with PED after a chemical corneal burn. Three weeks after the surgery, the PED was completely healed. This simple continuous suturing technique can allow firm and stable fixation of AM grafts on the ocular surface in cases of PED after chemical burn. It may prevent early loss of the graft and facilitate corneal epithelial wound healing.

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. [ABSTRACT FROM AUTHOR]

Autologous serum eye drops provide lubrication and promote epithelial healing. They have been successfully used in the management of ocular surface disorders such as dry eye disease, persistent epithelial defects and neurotrophic keratopathy for many decades. A great deal of variation in the methods of preparation of autologous serum eye drops, the end concentration and the duration of use exists in published literature. In this review, simplified recommendations for preparation, transport, storage and use of autologous serum are described. Evidence for the use of this modality in aqueous deficient dry eye disease is summarized, along with expertise‑based rationale. [ABSTRACT FROM AUTHOR]

Neurotrophic keratitis (neurotrophic keratopathy) (NTC) is a degenerative disease of the cornea accompanied with neurogenic inflammation. It is caused by a loss of sensitive innervation of the trigeminal nerve. Therapeutic measures are mainly reduced to maintenance therapy (antiseptics, artificial tears, corneal protectors), which does not affect the cause of the disease. The most affordable and updated therapy is the long-term topical use of auto- or heterologous serum. Recently developed specific approaches to the treatment of NTK — local therapy with recombinant nerve growth factor Cenegermin and corneal neurotization are aimed at the pathogenetic links of the disease and can restore the innervation and sensitivity of the cornea.

Objective To report three cases of side effects on ocular surface after receiving erlotinib, a kind of epidermal growth factor receptor (EGFR) inhibitor, and to analyze the reasons of different outcomes in these three cases. Methods Case series report. Results The patient in case 1 has been treated with erlotinib orally for nearly seven years. Ocular examination showed punctate epithelial defects on both eyes. Corneal epithelium recovered after eye drops treatment without discontinuation of erlotinib. The patient in case 2 has been treated with erlotinib for over two years. Sterile corneal ulcer with thinning of corneal stroma was present on one eye. After the patient underwent multilayer amniotic membrane transplantations and discontinued erlotinib for one week, the corneal epithelium gradually healed. In these two cases, besides lung cancer, there was no past medical history of hypertension, diabetes or other autoimmune diseases. However, in case 3, the patient had Sjögren syndrome besides lung cancer. After she was treated with erlotinib for over two years, severe ocular surface complications including persistent epithelial defect, corneal melting and perforation were not avoided and a total of four penetrating keratoplasties have been performed. Stable corneal surface was achieved after the erlotinib treatment was paused. Conclusions It is necessary to have detailed eye examinations before EGFR inhibitors treatment in order to exclude underlying ocular surface diseases, especially autoimmune ocular surface diseases. Meanwhile, regular ophthalmic follow-up should be performed during the use of these drugs to avoid severe side effects on ocular surface. [ABSTRACT FROM AUTHOR]

This case report aims to describe a modified continuous suturing technique for firm fixation of a human amniotic membrane graft in a patient with persistent epithelial defect (PED) after a chemical eye injury. As a result of this technique, the amniotic membrane (AM) was firmly fixed to the corneal surface with eight continuous and locked episcleral sutures that resembled an octagon graft. This technique was performed in a 14-year-old patient with PED after a chemical corneal burn. Three weeks after the surgery, the PED was completely healed. This simple continuous suturing technique can allow firm and stable fixation of AM grafts on the ocular surface in cases of PED after chemical burn. It may prevent early loss of the graft and facilitate corneal epithelial wound healing. [ABSTRACT FROM AUTHOR]

To present a case series of non-healing corneal ulcers treated by solid activated platelet-rich plasma (PRP) combined with silicone-hydrogel soft contact lens. Three eyes from three patients with unresponsive corneal ulcers were included. A clot of PRP was applied directly onto the corneal ulcer and covered with a soft contact lens. The primary outcome was corneal healing. Changes in corneal ulcer area were measured by analyzing slit-lamp photographs taken using ImageJ software. Successful corneal healing was achieved in all patients within two weeks, with no recurrences or signs of infection through the last follow-up. In two of the three cases, treatment was applied twice. This novel procedure was easy to perform, economically advantageous, and a possible alternative to surgical approaches for enhancing epithelial wound healing in patients with non-healing corneal ulcers. Further prospective and comparative studies are needed to assess the efficacy of this treatment. [ABSTRACT FROM AUTHOR]

Impairment in trigeminal nerve function causes a loss of corneal sensation and can lead to neurotrophic keratitis (NK). This gradual deterioration in the surface integrity of the cornea predisposes to the development of ulcers and may even progress to perforation, posing a risk for profound vision loss. Many common ophthalmic and systemic conditions, such as herpetic infections, ocular surgeries, neurosurgical procedures, multiple sclerosis and diabetes, can elicit NK by injuring the trigeminal nerve. Disease progression can occur rapidly and without symptoms, therefore, detecting NK early is critical. Management aims to halt continuing corneal damage and promote epithelial cell healing and nerve fibre regeneration. Novel treatment options show promise in restoring corneal sensitivity by re-establishing innervation, targeting the fundamental source of NK. [ABSTRACT FROM AUTHOR]

Neurotrophic keratitis (NK) is a rare degenerative condition that is caused by damage to the trigeminal nerve, with partial or complete loss of corneal sensory innervation. The loss of innervation leads to impaired healing of corneal epithelium, which subsequently results in punctate epithelial erosions, persistent epithelial defects, corneal ulcers and corneal perforation. Management of NK is often supportive and aims to promote epithelial healing and prevent progression of disease. Multiple novel pharmacological approaches have been proposed to address the underlying pathophysiology of NK, which are discussed in this paper. [ABSTRACT FROM AUTHOR]

Neurotrophic keratitis (NK) is a rare degenerative condition that is caused by damage to the trigeminal nerve, with partial or complete loss of corneal sensory innervation. The loss of innervation leads to impaired healing of corneal epithelium, which subsequently results in punctate epithelial erosions, persistent epithelial defects, corneal ulcers and corneal perforation. Management of NK is often supportive and aims to promote epithelial healing and prevent progression of disease. Multiple novel pharmacological approaches have been proposed to address the underlying pathophysiology of NK, which are discussed in this paper.

Purpose: To report a case of recurrent corneal ulcer caused by an oropharyngeal cavity pathogen. Observations: A patient presented with recurrent corneal ulcers with hypopyon. Leptotrichia species was eventually isolated from the corneal ulcer on bacterial polymerase chain reaction (PCR) after many negative bacterial culture attempts. Due to correct identification of the pathogen, it was discovered that the patient was exposing her eye to saliva. Modification of patient behavior and initiation of the appropriate antibacterial treatment resulted in resolution of recurrent episodes of active infection. Conclusions: Although Leptotrichia species are not typically ocular pathogens, they can become pathogenic in the cornea with direct transmission from the oral cavity to the eye.

Purpose: To study the indications and clinical outcomes, in a real-word setting, of amniotic membrane extract eye drops (AMEED) use for ocular surface disease (OSD). Methods: A retrospective study of patients treated with topical AMEED between January 2018 and January 2020 was conducted. Patients were classified in two groups according to specific OSD—dry eye disease (DED) and wound healing delay (WHD) groups. Demographics, comorbidities, treatment duration and clinical outcomes were analysed. Results: A total of 50 eyes of 36 patients with or without previous treatments were included. Patients in the DED group presented more systemic comorbidities (83 vs 22%; p < 0.001) and spent more mean time under AMEED treatment (10 vs 7.2 months average) than the WHD group (p = 0.0104). In four patients, long-term treatment (more than 24 months) was reported. Global similar symptomatic improvement was reported for both groups (DED 88.9% vs WHD 100%; p = 0.486), with the WHD group especially consisting in general relief (78%) and the DED group reporting more pain improvement (44%) (p = 0.011). Regarding patients with autologous serum as a previous treatment, no statistical differences were found in subjective or objective improvement. An overall success was achieved in 94.4% of the cases and no adverse events were found. Conclusion: AMEED administration is a promising mean to treat OSD such as dry eye, persistent epithelial defect and corneal ulcers. Although AMEED may be effective in the treatment of severe DED and persistent epithelial defect or corneal ulcers, conclusions are limited owing to the absence of controlled clinical trials. [ABSTRACT FROM AUTHOR]

Various etiologies, including diabetic keratopathy (DK), dry eye disease (DED), and neurotrophic keratopathy (NK), can disrupt corneal homeostasis, exacerbating corneal epithelial defects. Topical insulin has emerged as a promising therapy for promoting corneal wound healing and addressing underlying pathologies. This review systematically evaluates the efficacy of topical insulin across different corneal disorders. A literature review was conducted across the PubMed, Google Scholar, and Scopus research databases. The search resulted in a total of 19 articles, consisting of clinical trials, retrospective studies, and case reports. In DK, topical insulin accelerates corneal wound healing post-vitreoretinal surgery with lower concentrations showing higher outcomes when compared to conventional therapy, possibly due to improved epithelial stem cell migration. In comparison, the dry-eye disease results are inconclusive regarding patient-reported outcomes and corneal staining. For NK, topical insulin accelerates corneal wound healing and restores corneal nerve sensation. Other persistent epithelial defect (PED) etiologies that have been treated with topical insulin are infection, immune-mediated, mechanical and chemical trauma, and chronic ocular surface alterations. Although individual mechanisms for the benefits of topical insulin for each of these etiologies have not been studied, the literature demonstrates that topical insulin is efficacious for PEDs regardless of etiology. Future clinical trials need to be conducted to further evaluate optimal dosing, duration, and use of topical insulin for the restoration of the corneal surface., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Moin et al.)

Corneal calcification typically progresses slowly but can occasionally advance rapidly. This report details severe stromal calcification following repeat Descemet's stripping automated endothelial keratoplasty (DSAEK) in a 75-year-old patient with diabetes, hypertension, and prior ocular surgeries, including cataract surgery, intraocular lens extraction with suturing, and trabeculectomy. Persistent epithelial defects after the surgery led to rapid central stromal calcification within four weeks, significantly reducing visual acuity. Management included switching from betamethasone sodium phosphate to fluorometholone, facilitating complete epithelial recovery within two months. However, persistent stromal opacity necessitated a subsequent penetrating keratoplasty. Infrared absorption spectrophotometry identified calcium phosphate as the primary component of the calcification. This case highlights the importance of vigilant monitoring and proactive management of epithelial defects to prevent rapid calcification following endothelial keratoplasty., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Fukuto et al.)

Background: To develop a strategy based on surgical removal of a degenerated corneal epithelial scaffold for treatment of persistent epithelial defects (PEDs) in diabetic keratopathy. Case Presentation: Three diabetic patients with PEDs were initially treated with eyedrops containing the fibronectin-based peptide PHSRN (Pro-His-Ser-Arg-Asn) or both the substance P-derived peptide FGLM-NH2 and the insulin-like growth factor-1-derived peptide SSSR. A degenerated Bowman’s layer or calcified lesion thought to be responsible for incomplete healing was surgically removed after confirmation of reactivity to the peptide eyedrops. All three patients achieved complete epithelial wound closure after surgery. Two cases treated by phototherapeutic keratectomy or lamellar keratoplasty did not show PED recurrence during 6 or 36 months of follow-up, respectively. One case treated by mechanical removal of a degenerated Bowman’s layer manifested recurrence after 1 month, but resurfacing of the defect was again achieved after repeat surgery. Conclusion: We propose a new strategy for treatment of diabetic PEDs based on surgical remodeling of the corneal epithelial scaffold for patients who respond to peptide eyedrops but fail to achieve wound closure.

Rosacea is a dermatologic condition that affects the midfacial region. This chronic inflammatory disease can present with ocular manifestations distinguished by meibomian gland dysfunction, dry eye, and in severe cases, corneal ulceration and perforation. Neurotrophic keratopathy is an ocular condition with a reduced or absent corneal sensation associated with a corneal epitheliopathy. We present a 68-year-old man with both ocular rosacea and neurotrophic keratopathy who developed a corneal perforation. It was managed successfully with a tectonic keratoplasty in addition to topical steroids, lubrication, and oral tetracyclines. The perforation is explained by the superposition of both pathologies which lead to dry eye syndrome, along with chronic inflammation of the ocular surface. The effective follow-up and treatment of any epithelial defect in these patients is a major factor for corneal melting and perforation prevention. [ABSTRACT FROM AUTHOR]

Neurotrophic keratitis is an underdiagnosed degenerative condition induced by impairment to the corneal nerves which may lead to persistent epithelial defects and corneal blindness. Current medical and surgical treatments are only supportive and poorly tackle the underlying problem of corneal anesthesia; hence, fail to provide a permanent cure. Cenegermin is a newly introduced recombinant human nerve growth factor (rhNGF) that may address this issue. Preliminary clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis; however, the clinical experience with this drug is still limited. This review summarizes the pathogenesis and management of neurotrophic keratitis as well as the mechanism of action, uses, and limitations of cenegermin eye drops in the treatment of neurotrophic keratitis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the efficacy of allogeneic cultured limbal epithelial transplantation (ACLET) and cultivated oral mucosal epithelial transplantation (COMET) in treating total limbal stem cell deficiency (LSCD). Methods: In this retrospective cohort study, 73 patients (76 eyes) with total LSCD, including 41 patients (42 eyes) treated with ACLET and 32 patients (34 eyes) receiving COMET, were evaluated. The age, gender and injury cause of all patients were recorded. Results: The mean follow-up was 23.3 ± 9.9 months in the ACLET group and 16.1 ± 5.8 months in the COMET group. A higher incidence of persistent epithelial defect was observed after COMET (P = 0.023). The overall ocular surface grading scores were all lower in the ACLET group than in the COMET group at 3, 6, and 12 months after surgery and the last follow-up. Kaplan-Meier survival curve analysis demonstrated a significantly higher success rate of ACLET (71.4%), compared with that of COMET (52.9%; P = 0.043). The risk of graft failure was higher in patients with entropion and trichiasis, incomplete eyelid closure and treated with COMET. The graft failure risk rate after COMET was 3.5 times higher than that of ACLET. Conclusions: For total LSCD patients, ACLET should be prioritized, since limbal epithelial cells have better ability to maintain corneal epithelial integrity and ocular surface stability and benefit the ocular surface when compared with oral mucosal epithelial cells. Preoperative and postoperative eyelid abnormalities should be corrected as early as possible. [ABSTRACT FROM AUTHOR]

Joanna von Hofsten,1,2 Maria Egardt,2 Madeleine Zetterberg2–41Department of Ophthalmology, Halland Hospital Halmstad, Halmstad, 2Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, 3Department of Clinical Neuroscience and Rehabilitation, 4Department of Ophthalmology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenPurpose: The study aims to describe an intact cohort with mixed ocular surface disease (OSD) treated with autologous serum (AS) eye drops in a tertiary eye center.Patients and methods: All cases (n=32 eyes, 24 patients) treated with AS for OSD at the Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, between 2002 and 2013 were included and medical records were reviewed retrospectively.Results: Mean duration of treatment with 20% AS was 28.3±56.1 (median: 12, range: 3–217) days. The most common indication for AS treatment was a persistent epithelial defect (PED), which was seen in 16 eyes of 14 patients. Mean duration of PED prior to treatment was 19.3±18.9 (median: 10, range: 5–68) days. Complete or partial epithelial healing occurred in nine eyes (56.2%). The remaining seven eyes (44%) did not respond to treatment or data were missing. The second group consisted of nine eyes of five patients with superficial punctate keratitis (SPK) secondary to dry eye syndrome. Complete or partial healing of the epithelium occurred in five eyes (56%), and the remaining four eyes (44%) were lost to follow-up. A third group included five eyes with AS as an adjuvant treatment after corneal perforation, whereas a fourth group consisted of one patient with dry eye after laser-assisted in situ keratomileusis (LASIK).Conclusion: In this cohort, patients with PED or SPK responded well to treatment with AS. Standardized preparation protocols, defined optimal serum concentrations for various indications, and large randomized clinical trials are needed to fully comprehend the role of AS in the treatment of OSD.Keywords: dry eye syndrome, persistent epithelial defect, superficial punctate keratitis

Rosacea is a dermatologic condition that affects the midfacial region. This chronic inflammatory disease can present with ocular manifestations distinguished by meibomian gland dysfunction, dry eye, and in severe cases, corneal ulceration and perforation. Neurotrophic keratopathy is an ocular condition with a reduced or absent corneal sensation associated with a corneal epitheliopathy. We present a 68-year-old man with both ocular rosacea and neurotrophic keratopathy who developed a corneal perforation. It was managed successfully with a tectonic keratoplasty in addition to topical steroids, lubrication, and oral tetracyclines. The perforation is explained by the superposition of both pathologies which lead to dry eye syndrome, along with chronic inflammation of the ocular surface. The effective follow-up and treatment of any epithelial defect in these patients is a major factor for corneal melting and perforation prevention.

Purpose: The aim of the study was to assess the efficacy of a topical regenerating agent (RGTA) for management of persistent epithelial defects (PEDs) resistant to conventional therapy.Methods: Twenty-one patients (23 eyes) with PEDs despite the use of conventional therapy for lagophthalmos (n = 4), neurotrophic ulcer (n = 9), chemical burn (n = 3), Stevens-Johnson syndrome (n = 1), atopic keratoconjunctivitis (n = 1), severe dry eye (n = 2), peripheral ulcerative keratitis (n = 1), fungal keratitis (n = 1), and bacterial keratitis (n = 1) were enrolled in the study. Patients were treated with RGTA (Cacicol; Thea, Paris, France) instilled at a dosage of one drop on alternate days. Patients were evaluated by slit-lamp examination, anterior segment photography, and fluorescein-dye testing. Ulcer areas were noted on alternate days starting from the first day of instillation.Results: Twenty of 23 eyes (86.9%) displayed complete corneal healing after a mean period of ∼7.2 days (range, 2-20 days). Mean decrease ratio of ulcer area observed was 61.2% (range, 8.8%-100%, n = 19) on the 2nd day, 74.4% (range, 36%-100%, n = 16) on the 4th day, 80.2% (range, 43.7%-100%, n = 12) on the 6th day, 88.5% (range, 55.9%-100%, n = 9) on the 8th day, and 85.5% (range, 58.3%-100%, n = 7) on the 10th day. No significant differences were found in the epithelialization speed between eyes with and without bandage contact lenses in any postoperative day (P > 0.05). There were no treatment-related local or systemic side effects during the study.Conclusions: RGTA seems to be an effective therapeutic alternative in the treatment of persistent corneal epithelial defects. [ABSTRACT FROM AUTHOR]

Background: To develop a strategy based on surgical removal of a degenerated corneal epithelial scaffold for treatment of persistent epithelial defects (PEDs) in diabetic keratopathy. Case Presentation: Three diabetic patients with PEDs were initially treated with eyedrops containing the fibronectin-based peptide PHSRN (Pro-His-Ser-Arg-Asn) or both the substance P-derived peptide FGLM-NH2 and the insulin-like growth factor-1-derived peptide SSSR. A degenerated Bowman's layer or calcified lesion thought to be responsible for incomplete healing was surgically removed after confirmation of reactivity to the peptide eyedrops. All three patients achieved complete epithelial wound closure after surgery. Two cases treated by phototherapeutic keratectomy or lamellar keratoplasty did not show PED recurrence during 6 or 36 months of follow-up, respectively. One case treated by mechanical removal of a degenerated Bowman's layer manifested recurrence after 1 month, but resurfacing of the defect was again achieved after repeat surgery. Conclusion: We propose a new strategy for treatment of diabetic PEDs based on surgical remodeling of the corneal epithelial scaffold for patients who respond to peptide eyedrops but fail to achieve wound closure. [ABSTRACT FROM AUTHOR]

In order to maintain a smooth optical surface the corneal epithelium has to continuously renew itself so as to maintain its function as a barrier to fluctuating external surroundings and various environmental insults. After trauma, the cornea typically re-epithelializes promptly thereby minimizing the risk of infection, opacification or perforation. A persistent epithelial defect (PED) is usually referred to as a non-healing epithelial lesion after approximately two weeks of treatment with standard therapies to no avail. They occur following exposure to toxic agents, mechanical injury, and ocular surface infections and are associated with significant clinical morbidity in patients, resulting in discomfort or visual loss. In the case of deeper corneal injury and corneal pathology the wound healing cascade can also extend to the corneal stroma, the layer below the epithelium. Although significant progress has been made in recent years, pharmaco-therapeutic agents that promote corneal healing remain limited. This article serves as a review of current standard therapies, recently introduced alternative therapies gaining in popularity, and a look into the newest developments into ocular wound healing. [ABSTRACT FROM AUTHOR]

Pur po se: To evaluate the effect of autologous serum application on epithelization in the treatment of ocular surface disorders in hard cases and its safety. Ma te ri al and Met hod: Patients with serious ocular surface disorders, unresponsive to conventional treatment were recruited. Clinical features of retrospective cohort of patients who were prescribed serum drops are presented. From July 2007 to January 2010, 31 eyes of 21 patients, who were given autologous serum eye drops, were included into the study. Clinical examination included epithelial changes, rose bengal/lissamine green staining, fluorescein staining, and tear film break-up time. A history of systemic disease was recorded together with systemic medications used. A complete ocular history was also obtained. Re sults: Autologous serum was used in 7 patients with delayed epithelization after penetrating keratoplasty, in 4 patients with epithelial disturbances secondary to keratitis, in 2 patients with alkali burns, in 3 patients with Stevens-Johnson syndrome, in 1 patient with ligneous conjunctivitis, in 1 patient with epidermolysis bullosa, in 1 patient with corneal burn with hot water, and in 2 patients with Sjogren syndrome. The female:male ratio was 13:8. The mean age was 36.23±24.80 standard deviation (range: 7 months-87 years). No significant sight-threatening complication has been observed with the use of serum drops. Dis cus si on: Autologous serum application is safe and efficient additional therapy in the treatment of serious ocular surface problems in difficult cases. (Turk J Ophthalmol 2012; 42: 336-41)

Purpose: To evaluate continuous wear of a fluid-ventilated, gas-permeable scleral PROSE device using a standardized protocol as treatment for refractory persistent corneal epithelial defects in patients with severe ocular surface disease. Methods: Retrospective review of eight eyes of seven consecutive patients with persistent epithelial defects refractory to traditional therapies. The standardized treatment regimen consisted of: (1) 24-hour-a-day PROSE wear until re-epithelialization was achieved, (2) brief daily device removal, cleaning, disinfection, and reservoir fluid replacement, (3) addition of a benzalkonium chloride (BAK)-free fourth-generation fluoroquinolone antibiotic drop to the reservoir, and (4) transition to long-term, daytime PROSE wear upon re-epithelialization . Results: All eight eyes exhibited resolution of the persistent epithelial defect. No eyes developed microbial keratitis. Four eyes exhibited recurrences; all recurrences promptly responded to reinstitution of continuous wear. Conclusions: Continuous wear of a PROSE device, using a strictly standardized regimen, constitutes an effective, safe treatment option for refractory persistent epithelial defects. [ABSTRACT FROM AUTHOR]