Corneal Epithelial Breakdown Research Articles

Neurotrophic keratopathy: An updated understanding

PurposeTo propose an updated definition and staging system for neurotrophic keratopathy (NK) and provide consensus on diagnosis and treatment. MethodsA study group was convened to review the data pertinent to NK using a modified nominal group process. They proposed an updated definition for NK and a new 6-step staging system (Neurotrophic Keratopathy Study Group [NKSG] Classification) that can be used in conjunction with the different treatment options available currently or in the future. ResultsNK is defined as the dysfunction of corneal innervation that results in dysregulation of corneal and/or cellular function. It is characterized by loss of corneal sensation and neuronal homeostasis, leading to eventual corneal epithelial breakdown and ultimately keratolysis if untreated. The NKSG classification emphasizes verifying corneal sensation early and distinguishes different epithelial and stromal aspects of NK with the following stages: stage 1 (altered sensation without keratopathy), stage 2 (epitheliopathy/punctate epithelial keratopathy [PEK] without stromal haze), stage 3 (persistent/recurrent epithelial defects without stromal haze), stage 4 (epitheliopathy/PEK or persistent/recurrent epithelial defects with stromal haze), stage 5 (persistent/recurrent epithelial defect with corneal ulceration), and stage 6 (corneal perforation). Treatment consists of a variety of modalities (both indirect and direct). ConclusionsThis updated definition and staging system will provide clinicians with the necessary information to diagnose and treat NK at an early stage before it becomes a sight-threatening disorder. It also provides a framework for evaluating current and future treatment options at distinct stages of the disease.

The incidence and prevalence of recurrent corneal erosion syndrome in London, UK.

Recurrent corneal erosion syndrome (RCES) is caused by repeated episodes of corneal epithelial breakdown due to improper adherence of the corneal epithelium to the underlying basement membrane. The most common aetiologies are corneal dystrophy or previous superficial ocular trauma. The incidence and prevalence of the condition is currently unknown. This study aimed to determine the incidence and prevalence of RCES within the London population over a 5-year period in order to better inform clinicians and evaluate how this condition affects ophthalmic service provision. A retrospective cohort study over a 5-year period reviewed 487,690 emergency room patient attendances at Moorfields Eye Hospital (MEH) London between 1 January 2015 and 31 December 2019. MEH caters for a local population comprising of around ten regional clinical commissioning groups (CCGs). The data for this study were collected using OpenEyesTM electronic medical records including demographics and comorbidities. The CCGs encompass 41% (3,689,000) of London's total 8,980,000 inhabitants. Using these data the crude incidence and prevalence rates of disease were estimated with results reported per 100,000 population. Out of 330,684 patients, 3623 patients were given a new diagnosis of RCES by the emergency ophthalmology services, and from these, 1056 patients attended outpatient follow-up. The crude annual incidence of RCES was estimated at 25.4 per 100,000, with a crude prevalence rate of 0.96%. There was no statistical difference in annual incidence across the 5-year period. The period prevalence of 0.96% shows that RCES is not uncommon. There was also a stable annual incidence over the 5-year period, showing no changing trend over the study period. However, identifying the true incidence and period prevalence is a challenging task, as minor cases may heal prior to examination by an ophthalmologist. It is highly likely that RCES is underdiagnosed and therefore underreported.

Complicated Neurotrophic Corneal Ulcer in a Patient with Multiple Autoimmune Disorders

Neurotrophic keratitis is a rare degenerative corneal disease caused by impairment of trigeminal nerve innervation. This can lead to profound vision loss from corneal epithelial breakdown, ulceration, and in severe cases, perforation. This case report describes a 60-year-old male patient with multiple autoimmune diseases including Sjogren’s syndrome, Raynaud’s disorder, mixed connective tissue disorder, and Graves’ disease who presented with a complaint of blurred vision in his left eye due to a corneal ulcer. A careful analysis of the patient’s case history was crucial to arriving at the final diagnosis of a neurotrophic corneal ulcer. Although treated aggressively with topical antibiotics, artificial tears, and vitamin C, the corneal ulcer perforated 10 days later. Optometrists who choose to manage neurotrophic keratitis should be familiar with the potential complications and know when referral is needed. CE Notification This article is available as a COPE accredited CE course. You may take this course for 1-hour credit. Read the article and take the qualifying test to earn your credit. Click here to Enroll (https://www.crojournal.com/complicated-neurotrophic-corneal-ulcer-in-a-patient-with-multiple-autoimmune-disorders) Please check COPE course expiry date prior to enrollment. The COPE course test must be taken before the course expiry date.

Use of Autologous Serum Eye Drops with Contact Lenses in the Treatment of Chemical Burn-Induced Bilateral Corneal Persistent Epithelial Defects.

Objective We aim to evaluate the clinical effect of combined topical 20% autologous serum eye drops (ASEs) along with silicone–hydrogel soft contact lenses (SCLs) in the treatment of chemical burn-induced bilateral corneal persistent epithelial defects (PEDs) and to review the literature of related studies. Methods From January 1, 2017, to December 31, 2019, we conducted a retrospective chart review of 8 patients with chemical burn-induced bilateral corneal PEDs who were unsuccessfully treated with conventional medical therapy and were then treated with combined topical 20% (v/v) ASEs and silicone–hydrogel CLs. The clinical effects and effectiveness of the combined treatment were evaluated. Results The bilateral corneal PEDs healed in all sixteen eyes of the eight patients within 2 weeks. The patients did not report any discomfort associated with the combined treatment. Improved ocular comfort/visual acuity and decreased conjunctival injection correlated with healing. No recurrent corneal epithelial breakdown was noted during the 3-month posttreatment follow-up. Conclusions The combined treatment of silicone–hydrogel CLs and ASEs can help to stabilize the ocular surface and successfully treat chemical burn-induced bilateral corneal PEDs. It may be considered as an alternative treatment method for patients with bilateral chemical burn-induced corneal PEDs with potential corneal melting.

QS8: The Roles of the TrkA and p75NTR NGF Receptors in Corneal Wound Healing

Purpose: The cornea is the window through which we see the world and is one of the most densely innervated structures in the body. Besides providing protective sensory input, corneal nerves have been postulated to stimulate limbal stem cells (LSCs), hence governing corneal epithelial maintenance and recovery. Loss of corneal innervation, through injury, diabetes, tumors, infections, and even improper contact lens use, leads to neurotrophic keratopathy (NK), a degenerative corneal disease that is characterized by corneal epithelial breakdown, scarring, and permanent vision loss1. The only non-invasive treatment option for NK is the human recombinant nerve growth factor (rhNGF), but the short half-life of exogenous neurotrophins-based therapies make this therapeutic approach less effective2. Development of the small molecule ligands for neurotrophins receptors that have better pharmacokinetics and plasma stability showed promising results in the treatment of several neurodegenerative conditions in the recent years3. In this study, we were prompted to investigate the molecular mechanism of NK and the role of NGF receptors, TrkA and p75NTR, in corneal healing. We hypothesized that TrkA inhibition would delay corneal wound healing and p75NTR inhibition accelerates corneal healing. This knowledge will lay the basis for a new non-invasive approach for NK.Methods: For this experiment, we took advantage of commercially available Ntrk1 mutant mice, which allow for pharmacological inhibition of TrkA receptor with an inhibitor known as not mammalian kinase inhibitor (1-NM-PP1)4. Ntrk1 mice (n=20) were divided into three groups, which received saline injection as a control. In one experimental group animals were received TrkA inhibitor and the other group received both TrkA and p75 inhibitor for 5 days. On day six we removed the corneal epithelium with a 0.5 mm rotating brush. To measure epithelial healing, we performed digital imaging of fluorescein staining daily for four days after injury. We then harvested the corneas for immunofluorescent and biochemical analyses.Results: Our results show a significant delay in corneal epithelial healing following TrkA inhibition and acceleration in corneal healing after p75NTR inhibition.Conclusion: A selective TrkA agonist or p75NTR inhibitors could be a new therapeutic approach for NK.

Abstract 8: Corneal Neurotization Rescues the Corneal Epithelium from Thinning in a Rat Model of Neurotrophic Keratopathy

PURPOSE: The cornea is one of the most densely innervated tissues in the body, and in the absence of corneal sensory innervation, patients develop Neurotrophic Keratopathy (NK). NK is a disease characterized by corneal epithelial breakdown that can lead to progressive corneal scarring and ultimately, vision loss. Corneal neurotization uses nerve autografts to restore sensory innervation in the NK cornea.1,2 In our rat model of NK, we previously demonstrated that corneal neurotization with common peroneal and sural nerve grafts reduces epithelial breakdown, prevents scarring, and improves the rate of epithelial healing in the cornea3. Central corneal epithelial thinning is present in corneal denervation and NK. In the present study, we evaluate the effect of corneal neurotization on corneal epithelial and stromal thickness in a rat model of NK. METHODS: Previously validated models of NK and corneal neurotization were used in this study. The experimental groups were rats with i) NK (negative control) and ii) NK treated with corneal neurotization (treatment), and the control group consisted of rats with normally innervated corneas. In the experimental groups, NK was achieved with stereotactic ablation of the ophthalmic nerve. Four weeks after ablation, affected corneas (n=5 per group) were harvested. Three 10μm cross-sections from each cornea, sampled from representative areas of the cornea, were stained with Hematoxylin and Eosin for analysis. Each section was imaged with bright-field microscopy at 200X magnification. The epithelial and stromal thicknesses of each section were measured using ImagePro. Mean thicknesses were compared using the Kruksal-Wallis test and unpaired t-tests. RESULTS: The central epithelial thickness of the NK corneas (15.83 ± 1.62) was significantly decreased compared to that of the central epithelium in the treated (25.07 ± 3.89, p < 0.05) and normally innervated corneas (24.75 ± 2.46, p < 0.05), the treated and normally innervated corneas not being significantly different. In contrast, the stromal thicknesses were insignificantly different in all three groups. CONCLUSIONS: Corneal neurotization rescues the NK cornea from central epithelial thinning, suggesting the reinnervating axons of the inserted graft restore corneal epithelial integrity. We are pursuing further research with the same rat models of NK and corneal neurotization to elucidate the underlying mechanisms. REFERENCES: 1. Elbaz U, Bains R, Zuker RM, Borschel GH, Ali A. Restoration of corneal sensation with regional nerve transfers and nerve grafts: A new approach to a difficult problem. JAMA Ophthalmol. 2014;132(11):1289–1295. doi:10.1001/jamaophthalmol.2014.2316 2. Bains RD, Elbaz U, Zuker RM, Ali A, Borschel GH. Corneal neurotization from the supratrochlear nerve with sural nerve grafts: A minimally invasive approach. Plast Reconstr Surg. 2015;135(2):397e-400e. doi:10.1097/PRS.0000000000000994 3. Catapano J, Antonyshyn K, Zhang JJ, Gordon T, Borschel GH. Corneal neurotization improves ocular surface health in a novel rat model of neurotrophic keratopathy and corneal neurotization. Investig Opthalmology Vis Sci. 2018;59(11):4345–4354.

Ocular Surface Morbidity in Eyes with Senile Sunken Upper Eyelids

To report ocular surface findings in eyes manifesting senile sunken upper eyelids. Cross-sectional comparative case series. A study group of 38 eyes of 38 patients with sunken upper eyelids was compared with a control group of 26 age- and gender-matched patients without sunken upper eyelids. Patient records were retrieved and compared between the 2 groups and among different severities of sunken upper lids. Ocular surface deficits were measured by symptoms, eyelid blinking and closure, Bell's phenomenon, apposition of lids and puncta to the globe, conjunctiva inflammation and chalasis, corneal epithelial breakdown by fluorescein and Rose Bengal staining, and the fluorescein clearance test. Ocular irritation or pain was less common, but tearing and mucous buildup were more common in the study group than the control group, and it tended to be worse in the morning. Incomplete blinking, incomplete closure, abnormal Bell's phenomenon, lid/punctum ectropion, and delayed tear clearance were more frequently detected in the study group than the control group and were more evident in severely affected eyes. Incomplete blinking was significantly correlated with incomplete closure, whereas abnormal Bell's phenomenon was significantly correlated with early morning symptoms. Conjunctivochalasis was less common in the study group than the control group. Corneal epithelial breakdown was more common in the study group than the control group, and was more severe in severely affected eyes. Sunken upper eyelids are associated with ocular surface morbidity characterized by corneal epithelial breakdown because of an array of ocular surface deficits leading to exposure and desiccation, not only during the day but also in the night. Recognition of this potential risk factor will help to understand pathogenesis and formulate effective therapies in complex ocular surface diseases. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Breakdown Evaluation of Corneal Epithelial Barrier Caused by Antiallergic Eyedrops Using an Electrophysiologic Method

The aim of this study was to examine the usefulness of an electrophysiologic method for predicting corneal epithelial breakdown by antiallergic eyedrops and comparing the results with those in other appraisal methods. Six kinds of antiallergic eyedrops, including benzalkonium chloride (BK) as an ophthalmic preservative and two kinds of BK-free antiallergic eyedrops, were used in this study. Eyedrops were applied to excise rabbit corneas and monitoring was performed according to an electrophysiologic method, using a commercially available chamber system to mimic human tear turnover. Changes in transepithelial electrical resistance (TEER) in the corneal surface were recorded. The cytotoxicity of each kind of eyedrops in a normal rabbit corneal epithelial (NRCE) cell line and a human endothelial cell line EA.hy926 was also examined. The extent of decrease in the corneal TEER after applying antiallergic eyedrops was dependent on the concentration of the BK included as a preservative, but it was also affected by the different kinds of drugs when the BK concentration was low. Higher cytotoxicity of the eyedrops against the NRCE and EA.hy926 cell lines was observed with a reduction of TEER. Monitoring changes in the corneal TEER, according to the electrophysiologic method with the application of antiallergic eyedrops, is useful for predicting corneal epithelial breakdown caused by their instillation.

Ocular Indigo Dye Injury

To describe the clinical course, management, and final outcome in a case of ocular injury caused by accidental fall of indigo dye in both eyes. Review of patient's record and relevant literature. A 32-year-old man sustained ocular injury caused by inadvertent indigo dye in both eyes. He presented with bluish staining of the entire ocular surface, subtotal corneal epithelial breakdown in both eyes, and entry of dye into the anterior chamber in the left eye. This was treated as acute alkali burns with lubricants and steroids. Over a period of 3 to 4 months, the ocular surface staining resolved completely, and visual acuity improved remarkably. Although the clinical presentation was initially a cause for concern, the condition resolved completely with the same conservative management as applicable for other chemical injuries.

Eye care in ICU

Context: Patients in intensive care units have impaired ocular protective mechanisms, resulting in a high risk of developing eye complications. Various eye care protocols are being used, but none is proven to be absolutely effective. Aims: To compare the efficacy of using a combination of ocular lubricants and securing tape over the eyelids (Open chamber method), with use of swimming goggles and regular moistening of eyelids with gauze soaked in sterile water (Closed chamber method), to prevent corneal epithelial breakdown in the sedated and semiconscious intensive care adult patient. Settings and Design: A randomized clinical study was performed. Patients with Glasgow coma scale score of £ 10/15, admitted into the Medical ICU of a large teaching hospital, over a four month duration, were studied. Materials and Methods: Patients were examined daily by an Ophthalmologist, using a portable slit lamp and the patient's corneas were tested daily using 1% Fluorescein drops. Standard grading scales were used to record eyelid position and corneal and conjunctival changes. Statistical analysis used: Quantitative variables were described in terms of their relative frequencies in proportions. Null hypothesis was applied to derive the statistical significance of the observed variations in both the treatment groups. Chi-square test for relationships was used to assess the effect of specific variables on the development of keratopathy. Results: Sixty one patients (122 eyes) in the open chamber group and 63 (126 eyes) in the closed chamber group, were analyzed. Incomplete lid closure was seen in 74 eyes (30%). Exposure keratopathy was noticed in 39 eyes (32%) in open chamber group and ten (8%) in closed chamber group and was more severe in the former group. There was no difference in the incidence of conjunctival oedema in both groups. Incomplete lid closure and use of muscle relaxants, were significant risk factors for developing keratopathy. Conclusions: Use of swimming goggles and regular moistening of eyelids with gauze soaked in sterile water providing a moisture chamber, is more effective than using a combination of ocular lubricants and securing tape over the eyelids, in preventing corneal epithelial breakdown in sedated and semiconscious intensive care unit patients.

Efficacy of gold weight implants in facial nerve palsy: quantitative alterations in blinking.

Deficient eyelid closure is a major visual threat to patients with unresolved facial nerve palsy. Gold weight implants assisted eyelid closure in patients with paresis of the orbicularis oculi, ameliorating patient complaints of dry eye, excessive tearing, and corneal epithelial breakdown. We used dynamic measures to assess the efficacy of upper eyelid gold weight implantation surgery for facial nerve palsy. The search coil technique was used to record spontaneous blinks bilaterally in six patients, before and after unilateral gold weight implantations into the upper eyelid in severe facial nerve palsy. In uncomplicated facial nerve palsy, the amplitude of blink down-phases for the paretic eyelid was 28.6 +/- 5.7% of the amplitude of the contralateral, normal eyelid. Following corrective surgery, closure of the paretic eyelid improved to 42.6 +/- 7.5% (P < 0.05). There was not a commensurate increase in the peak velocity of blink down-phases, suggesting that gold weight effects are mediated by a passive improvement in blink dynamics.

Moisture chamber versus lubrication for the prevention of corneal epithelial breakdown

Patients who are comatose or semicomatose are at risk of corneal dryness and ulceration. To compare and evaluate the effectiveness of two treatments used for the prevention of corneal epithelial breakdown in critically ill patients. A randomized clinical trial was used. The sample consisted of critically ill patients (age, 15-84 years) with a limited or absent blink reflex in a 14-bed general intensive care unit in a large metropolitan teaching hospital. Ninety-six eligible patients were studied; of these, 36 were excluded and data from the remaining 60 patients were analyzed. Patients were randomized to receive methylcellulose lubricating drops every 2 hours (n = 30) or to have their eyes covered with a polyethylene film to create a moisture chamber (n = 30). The patients' corneas were tested daily for epithelial breakdown using fluorescein drops. Patients were studied for a minimum of 48 hours and a maximum of 1 week. Eight of the 30 patients in the lubricating drop group had positive fluorescein staining, compared with one in the moisture chamber group. Our results suggest that a moisture chamber is more effective than lubricating drops in preventing corneal epithelial breakdown in critically ill patients with limited or absent blink reflex.

5-Fluorouracil-Injektionsbehandlung nach fistulierenden Glaukomoperationen

Since 1984 subconjunctival 5-Fluorouracil injections have been applied with success after filtering surgery. It was the purpose of this retrospective study to find out whether the results justify this treatment in view of all side effects. Between 2/1991 and 1/1993 twenty-nine eyes of 11 female and 16 male patients with high-risk glaucoma (unsuccessful previous filtering surgery and a high risk of scarring) were treated with subconjunctival injections of 5-Fluorouracil after filtering surgery in the University Eye Hospital Düsseldorf. The mean age of the patients was 58 (11-84) years and the mean follow-up period was 16 (4-24) months. The mean amount of injected 5-Fluorouracil was 43 (5-85) mg. Glaucoma was regarded as controlled when intraocular pressure levels were reduced by more than 20% of the preoperative level and stayed consistently below 21 mm Hg. 26 (89.6%) of the eyes had controlled intraocular pressure during the follow-up period. Two eyes were controlled only after additional cyclocrycoagulation, and 1 glaucoma has remained uncontrolled. Postoperatively we observed fistulas of the conjunctiva in 24% of the eyes and 69% of the eyes had corneal epithelial breakdown problems. It is unlikely that subconjunctival injections of 5-Fluorouracil work only by inhibiting scarring of the filtration bleb. Long-lasting e-vacuo-symptoms in single cases with no functioning bleb at all as well as scarred blebs in 9 of 26 eyes with controlled glaucoma must be interpreted as a probable sign of 5-Fluorouracil toxicity on the ciliary epithelium. Subconjunctival injections of 5-Fluorouracil after filtering surgery are helpful to control high-risk glaucoma, but there are several disadvantages of this treatment as fistulas of the conjunctiva, corneal surface problems, discomfort for the patient, difficult follow-up and a potential toxicity on the ciliary epithelium that may be pronounced in some cases. Therefore, subconjunctival injections of 5-Fluorouracil after filtering surgery are a useful means for eyes with a high risk of scarring. However, 5-Fluorouracil should not be applied for primary normal glaucoma surgery.