Search Results (24)

Lamellar ichthyosis is a rare congenital disorder of keratinization frequently associated with ocular complications, most commonly cicatricial ectropion and exposure keratopathy. We present a case of severe mixed exposure-related and neurotrophic keratopathy with marked corneal thinning in a 61-year-old man with genetically confirmed lamellar ichthyosis. At presentation, the best-corrected visual acuity (BCVA) in the right eye was limited to hand motion (logMAR 2.3). Slit-lamp examination revealed a large central to inferocentral corneal ulcer measuring approximately 3 × 4 mm with severe stromal thinning in the setting of marked lower eyelid ectropion, incomplete eyelid closure, and chronic ocular surface exposure, while anterior segment optical coherence tomography (AS-OCT) demonstrated a minimal corneal thickness of approximately 165 µm. Microbiological swabs obtained from the conjunctival sac were negative, and no purulent discharge, hypopyon, or anterior chamber inflammatory reaction was present, making active infectious keratitis unlikely. Corneal sensitivity measured with Cochet–Bonnet esthesiometry at presentation, centrally and in all four peripheral quadrants of both eyes, was markedly reduced, more severely in the affected right eye, supporting the presence of a severe neurotrophic component contributing to impaired corneal healing. Intensive conservative therapy including preservative-free lubricants, dexpanthenol gel, autologous serum eye drops, topical insulin, prophylactic antibiotics, and systemic doxycycline was initiated. Serial AS-OCT imaging demonstrated progressive structural recovery, with corneal thickness increasing to 438 µm after one month of treatment and complete corneal epithelialization. The BCVA improved to 0.2 Snellen (0.7 logMAR). This case highlights the diagnostic value of multimodal anterior segment imaging in monitoring severe mixed keratopathy with advanced corneal thinning and demonstrates that intensive conservative therapy may stabilize the ocular surface and prevent corneal perforation in patients with lamellar ichthyosis. Full article

The ocular surface is a neuro–epithelial–immune unit in which corneal innervation is essential for maintaining tissue integrity and visual function. Sensory nerves regulate reflex tearing and blinking, provide trophic support, and modulate local immune responses. Nerve injury resulting from trauma, surgery, infection, systemic disease, or chronic inflammation disrupts epithelial homeostasis and may lead to neurotrophic keratopathy, neuropathic pain, and pathological remodeling. Beyond classical neurotrophic disease, nerve dysfunction contributes to severe dry eye and immune-mediated cicatricial disorders. Depending on the neuro-inflammatory context, remodeling may evolve toward stromal thinning, as in keratoconus, or progressive fibrosis, as in ocular cicatricial pemphigoid. Blood-derived eye drops, including serum- and platelet-based formulations, represent biologically active therapies that support epithelial repair and nerve regeneration, although greater standardization is needed. Full article

Eye drops derived from human blood components (Eye Drops of Human Origin—EDHO) have proven effective in reducing ocular pain associated with severe keratopathies. Among these, Cord Blood Serum (CBS) is particularly promising for its high content of growth and neurotrophic factors. This study evaluated the ability of CBS to modulate inflammatory and nociceptive activation in the human conjunctival epithelial cell (HCEC) line exposed to hyperosmotic stress. CBS batches were characterized for brain-derived neurotrophic factor (BDNF) content and classified as CBS_high (levels > 18.0 ng/mL) or CBS_low (levels < 10.0 ng/mL). HCECs were exposed to NaCl (450 mOsm/L) with or without 5% CBS. Cell viability was evaluated, and the expression of Major Histocompatibility Complex Class II (HLA-DR) (a marker of immune activation) and Transient Receptor Potential Vanilloid 1 (TRPV1) (a nociceptive ion channel responsive to osmotic stress) was assessed via Real Time PCR (RT-PCR). CBS significantly improved HCEC viability under hyperosmotic stress. Exposure to NaCl alone upregulated HLA-DR and TRPV-1 expression. Both CBS preparations attenuated these responses, producing comparable reductions in HLA-DR mRNA and decreasing TRPV-1 expression. Partial reversal of CBS effects by the pan-neurotrophin receptor inhibitor K252a supported neurotrophin involvement. CBS reduces hyperosmolarity-driven inflammation and nociception via HLA-DR and TRPV1 downregulation, supporting its role as a bioactive tear substitute in neuroinflammatory ocular surface disease. Full article

Corneal nerves play a crucial role in maintaining ocular surface homeostasis by supporting the functional integrity of corneal epithelial, stromal, and endothelial cells; modulating tear secretion; and facilitating sensory responses essential for overall ocular health. With advancing age, these highly specialized peripheral sensory fibers undergo progressive attrition and morphologic distortion driven by the canonical hallmarks of aging including genomic instability, impaired proteostasis, mitochondrial dysfunction, and chronic low-grade inflammation. The resulting neuro-immune dysregulation reduces trophic support, delays wound healing, and predisposes older adults to dry-eye disease, neurotrophic keratopathy, and postsurgical hypoesthesia. Age-exacerbating cofactors including diabetes, dyslipidemia, neurodegenerative disorders, topical preservatives, chronic contact-lens wear, herpes zoster ophthalmicus, and ocular-surface hypoxia further accelerate sub-basal nerve rarefaction and functional decline. This review provides an overview of age-related physiological alterations in ocular surface nerves, with a particular emphasis on corneal innervation. It also discusses risk factors that speed up these changes. Given the inherently limited regenerative capacity of corneal nerves and their inability to fully restore to baseline conditions following injury or degeneration, it is critical to identify and develop effective strategies aimed at mitigating or delaying physiological nerve degeneration and promoting nerve regeneration. This review also brings up emerging therapeutic strategies, including regenerative medicine, neuroprotective agents, and lifestyle interventions aimed at mitigating age-related corneal nerve degeneration. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Corneal sensitivity is an important indicator of corneal health and innervation. Corneal hypoesthesia may be an early indicator of corneal diseases such as neurotrophic keratopathy. Various instruments have been used to measure corneal sensitivity, the first being the Cochet–Bonnet aesthesiometer. Over the years, new devices employing different stimuli have been developed, such as the gas-based Belmonte aesthesiometer, the Swiss liquid-jet aesthesiometer, and the most recently released corneal Brill aesthesiometer. In this review, the progress and advancement of aesthesiometers since their introduction is described. The mechanism, advantages, and disadvantages of these aesthesiometers are discussed and compared. We also report the relationship between corneal sensitivity and corneal innervation in various conditions, including diabetes mellitus, Fuchs’ endothelial dystrophy, dry eye disease, glaucoma, keratoconus, herpes simplex keratitis, post-refractive surgery, and ocular graft-versus-host disease. Through this review, we aim to highlight the importance of the assessment of corneal sensitivity and innervation in the diagnosis, treatment, and monitoring of anterior and posterior segment ocular disorders. Full article

This review explores the potential role of topical insulin drops in corneal regeneration by analyzing the mechanism of action and clinical outcomes. Corneal integrity restoration is crucial for ocular surface healing. This review synthesizes the current literature on topical insulin for neurotrophic keratopathy (NK), highlighting its mechanism of action, therapeutic potential, and clinical outcomes. Recent studies report high rates of epithelial regeneration, suggesting that topical insulin may be an effective adjunct or alternative to conventional treatments. Further randomized controlled trials are needed to confirm its long-term efficacy and optimal dosing. Methods: Considering the limited regenerative capacity of the corneal epithelium in NK and the increasing interest in novel therapy, we review the existing literature to evaluate the role and extent of topical insulin’s contribution to corneal healing by applying the PICO framework, which allows for a clear and systematic approach to literature selection and evaluation. The literature search and study selection were conducted manually following PRISMA guidelines. Conclusions: Most of the studies resulting from the selection have small samples, and there is a lack of large, randomized clinical trials. The evidence reviewed in this study suggests that topical insulin is a promising therapy for promoting corneal healing in neurotrophic keratopathy. While clinical trials have demonstrated significant epithelial regeneration, optimal dosing and long-term safety require further investigation. Compared to conventional treatments such as autologous serum or growth factor therapy, insulin eye drops provide a cost-effective alternative. Additional research through controlled trials is needed to formulate standardized therapeutic protocols and verify long-term outcomes. Full article

The ocular surface is susceptible to a wide spectrum of inflammatory, degenerative, and neurotrophic diseases that can impair vision. The complex pathophysiology and limited therapeutic options associated with these conditions continue to pose significant clinical challenges. Nerve Growth Factor (NGF), a neurotrophin initially recognized for its role in neuronal survival and differentiation, has emerged as a key regulator of ocular surface homeostasis and repair. Beyond its neurotrophic functions, NGF is suggested to influence epithelial proliferation, immune responses, tear secretion, and angiogenesis. Experimental and clinical studies have implicated NGF in both the pathogenesis and potential treatment of various ocular surface diseases, including allergic conjunctivitis, neurotrophic keratopathy (NK), immune-mediated and herpetic keratitis, and dry eye disease (DED), as well as post-surgical corneal wound healing. Notably, recombinant human NGF (rhNGF, cenegermin) has been approved as the first topical biologic therapy for NK. Despite encouraging clinical outcomes, challenges such as high treatment costs, limited long-term data, and potential proangiogenic effects remain. This review consolidates current evidence on the role of NGF in ocular surface health and disease, highlighting its biological mechanisms, clinical applications, and future therapeutic potential. Full article

Neurotrophic keratopathy (NK) is a rare degenerative disease caused by impairment of the trigeminal nerve, leading to corneal anesthesia, epithelial breakdown, and progressive vision loss. Conventional treatments primarily focus on symptom management and the prevention of complications, but they do not address the underlying nerve dysfunction. Corneal neurotization (NT) has emerged as a promising surgical intervention aimed at restoring corneal sensation and improving ocular surface homeostasis. This review evaluates the outcomes of corneal neurotization in patients with NK and compares the effectiveness of direct (DNT) and indirect (INT) techniques. Studies have reported significant improvements in corneal sensitivity, with success rates ranging from 60.7% to 100% (mean: 90%). Most patients experienced recovery of corneal sensation, as measured by the Cochet–Bonnet aesthesiometer, with no significant differences in outcomes between DNT and INT. Indirect neurotization using a sural nerve graft was the most commonly employed technique (63% of cases), while the use of acellular allografts demonstrated comparable efficacy and simplified the procedure. Postoperative corneal sensitivity increased significantly, from a preoperative average of 2.717 mm to 36.01 mm, with reinnervation typically occurring within 4–6 months and peaking at 12 months. In vivo confocal microscopy confirmed the presence of nerve regeneration. Neurotization was found to be safe, with minimal donor-site complications, which generally resolved within one year. Although the procedure improves corneal sensation and tear film stability, visual acuity outcomes remain variable due to pre-existing corneal damage. Early intervention is, therefore, recommended to prevent irreversible scarring. However, the number of patients undergoing the procedure remains limited, making it difficult to draw definitive conclusions. Most available studies consist of small case series. Further research with larger sample sizes is needed to refine surgical techniques and optimize patient selection, thereby improving outcomes in the management of NK. Full article

Neurotrophic keratopathy (NK) is a degenerative corneal disease characterized by impaired corneal sensitivity and epithelial repair that is often linked to sensory nerve dysfunction. To establish a clinically relevant model and explore the mechanisms underlying NK pathogenesis, we developed a novel mouse model through partial transection of the ciliary nerve. This approach mimics the progressive nature of NK, reproducing key clinical features such as corneal epithelial defects, reduced sensitivity, diminished tear secretion, and delayed wound healing. Using this model, we investigated how disruptions in mitochondrial dynamics contribute to corneal epithelial dysfunction and impaired repair in NK. Our findings revealed substantial disruptions in mitochondrial dynamics, including reduced expression of fusion proteins (OPA1), downregulation of fission regulators (FIS1 and MFF), and impaired mitochondrial transport, as evidenced by decreased expression of Rhot1 and Kif5b. Additionally, the downregulation of mitophagy-related genes (Pink1 and Prkn) contributed to the accumulation of dysfunctional mitochondria, leading to DNA damage and impaired corneal epithelial repair. These mitochondrial abnormalities were accompanied by increased γH2AX staining, indicative of DNA double-strand breaks and cellular stress. This study highlights the pivotal role of mitochondrial dynamics in corneal epithelial health and repair, suggesting that therapeutic strategies aimed at restoring mitochondrial function, enhancing mitophagy, and mitigating oxidative stress may offer promising avenues for treating NK. Full article

Background: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder characterized by the formation of intranuclear inclusions in cells. Adult-type NIID usually develops in elderly patients with various clinical manifestations and is sometimes accompanied by ocular symptoms. A case of adult-onset NIID with early and unique manifestations, including a progressive corneal defect and retinal changes, which are concerning at a young age, is reported. Case Presentation: A 29-year-old woman with adult sporadic NIID presented to our department with a progressive corneal disorder. Her neurological symptoms started at the age of 22 years, and she was diagnosed with NIID by skin biopsy and genetic testing. Ocular examination revealed bilateral corneal superficial punctate keratitis, right corneal opacity, decreased vision, nocturnal lagophthalmos, and early retinal changes. Corneal nerve fiber atrophy was detected by in vivo confocal microscopy. With a Cochet–Bonnet aesthesiometer, the progression of NIID and decreased corneal sensation were confirmed. Findings consistent with neurotrophic keratitis and keratoconjunctivitis due to nocturnal lagophthalmos were both suggested as being complications of her underlying NIID. Treatment with punctal plugs, sodium hyaluronate eye drops, diquafosol sodium eye drops, systemic and local antivirals, and local steroid medications resulted in the gradual improvement in the irregularity and opacity of the epithelium. Conclusions: NIID may lead to neurotrophic keratopathy due to impairment of the corneal sensory nerves. Nocturnal lagophthalmos is a remarkable finding in a case of NIID. The findings in the present case highlight the complex and multifaceted nature of NIID, with neurological and ocular manifestations requiring a multidisciplinary approach to management. Full article

The measurement of corneal sensation allows clinicians to assess the status of corneal innervation and serves as a crucial indicator of corneal disease and eye health. Many devices are available to assess corneal sensation, including the Cochet–Bonnet aesthesiometer, the Belmonte Aesthesiometer, the Swiss Liquid Jet Aesthesiometer, and the newly introduced Corneal Esthesiometer Brill. Increasing the clinical use of in vivo confocal microscopy and optical coherence tomography will allow for greater insight into the diagnosis, classification, and monitoring of ocular surface diseases such as neurotrophic keratopathy; however, formal esthesiometric measurement remains necessary to assess the functional status of corneal nerves. These aesthesiometers vary widely in their mode of corneal stimulus generation and their relative accessibility, precision, and ease of clinical use. The development of future devices to optimize these characteristics, as well as further comparative studies between device types should enable more accurate and precise diagnosis and treatment of corneal innervation deficits. The purpose of this narrative review is to describe the advancements in the use of aesthesiometers since their introduction to clinical practice, compare currently available devices for assessing corneal innervation and their relative limitations, and discuss how the assessment of corneal innervation is crucial to understanding and treating pathologies of the ocular surface. Full article

The article introduces neurotrophic keratopathy (NK), a condition resulting from corneal denervation due to various causes of trigeminal nerve dysfunctions. Surgical techniques for corneal neurotization (CN) have evolved, aiming to restore corneal sensitivity. Initially proposed in 1972, modern approaches offer less invasive options. CN can be performed through a direct approach (DCN) directly suturing a sensitive nerve to the affected cornea or indirectly (ICN) through a nerve auto/allograft. Surgical success relies on meticulous donor nerve selection and preparation, often involving multidisciplinary teams. A PubMed research and review of the relevant literature was conducted regarding the surgical approach, emphasizing surgical techniques and the choice of the donor nerve. The latter considers factors like sensory integrity and proximity to the cornea. The most used are the contralateral or ipsilateral supratrochlear (STN), and the supraorbital (SON) and great auricular (GAN) nerves. Regarding the choice of grafts, the most used in the literature are the sural (SN), the lateral antebrachial cutaneous nerve (LABCN), and the GAN nerves. Another promising option is represented by allografts (acellularized nerves from cadavers). The significance of sensory recovery and factors influencing surgical outcomes, including nerve caliber matching and axonal regeneration, are discussed. Future directions emphasize less invasive techniques and the potential of acellular nerve allografts. In conclusion, CN represents a promising avenue in the treatment of NK, offering tailored approaches based on patient history and surgical expertise, with new emerging techniques warranting further exploration through basic science refinements and clinical trials. Full article

Background: Boston Keratoprosthesis Type I (BI-KPro I) is a synthetic cornea that can be used to restore vision in patients with corneal blindness. This retrospective study evaluated the outcomes of BI-KPro implantation in 118 patients. Material: The mean age of the patients was 56.76 ± 14.24 years. Indications for keratoprosthesis implantation were as follows: graft failure, 47 (39.83%); ocular burn, 38 (32.20%); neurotrophic keratopathy, 11 (9.32%), mucous membrane pemphigoid 9 (7.67%); autoimmune, 6 (5.08%); Stevens–Johnson syndrome, 4 (3.39%); and aniridia (2.54%). Methods: The surgeries were performed between March 2019 and June 2022 at a single clinical center in two locations. The postoperative visual acuity, complications, and need for additional surgical procedures were analyzed. Results: The Best Corrected Visual Acuity before surgery was 0.01 ± 0.006. After one year (V1), it was 0.30 ± 0.27; at two years (V2), it was 0.27 ± 0.26; and at three years (V3), it was 0.21 ± 0.23. The percentage of patients with visual acuity better than 0.1 on the Snellen chart was 37.29% after 1 year, 49.35% after 2 years, and 46.81% after 3 years of follow up. The most common complications were glaucoma (78 patients; 66.1%), corneal melting (22 patients; 18.6%), and retroprosthetic membranes (20 patients; 17.0%). Conclusions: The BI-KPro can significantly improve visual acuity. The worst long-term results were obtained in the group of patients with autoimmune diseases; therefore, careful consideration should be given to implanting BI-KPro in this group. The high incidence of de novo glaucoma or the progression of pre-existing glaucoma suggests the need for careful monitoring. Full article

Neurotrophic keratopathy is a corneal disease characterized by impaired corneal innervation. It can lead to corneal epithelial defects, ulcerations, and perforations. Topical insulin has been shown to be effective in treating this disorder. Insulin is a growth factor that can promote corneal epithelial cell proliferation and migration. In addition, it can also inhibit corneal epithelial cell apoptosis. Topical insulin has previously been found to enhance corneal wound healing. This article reviews the current understanding of the mechanism of action of topical insulin in the treatment of neurotrophic keratopathy. Full article