Corneal Ulcer Research Articles

ACTUALIZATION AUTOSCLEROKERATOPLASTY IN CORNEAL DISEASES

Rationale: Diseases of the cornea of the eye account for a quarter of the total incidence of ophthalmological pathologies, which, in turn, are detected in 11% of all cases of appeals. These pathologies are dangerous, since 75% of patients with this group of diseases may subsequently develop visual impairment, up to its complete loss. In case of severe lesions, surgical intervention is inevitable, while both allo- and autografts can be used for corneal flap transplantation, with the sclera being the most preferred option in this case. Autosclerokeratoplasty seems to be a modern, most rational method for treating severe pathologies of the cornea, and updating this method seems to be a very important task.Objective: updating the method of autosclerokeratoplasty for corneal lesions using a clinical example of the successful use of the method for ulcerative lesions of the cornea.Methods: An analytical work of scientific literature for the last 10 years was carried out, PubMed databases were used, including PubMed Central, Google Scholar, CyberLeninka. The search was conducted using the keywords “autosclerokeratoplasty”, “autosclera”, “corneal ulcer”, etc.To characterize the possibility of using autosclerokeratoplasty in clinical practice for corneal damage, a clinical case is given, medical documentation was used for the analysis: outpatient card, medical history, instrumental and physical examination data. The data were systematized using modern methods of information analysis.Results: The method has many advantages over other methods of surgical treatment of corneal pathologies: 1) performing anterior lamellar keratoplasty of the cornea allows to reliably close the optical zone, eliminating the threat of perforation and in some cases improve the patient’s vision, 2) in case of a threat of rejection of the lamellar keratograft, it is possible to take a second peripheral fragment of the cornea under the upper eyelid, 3) suture fixation of the autoscleral flap over the area ofthe corneal defect under the upper eyelid allows to achieve an aseptic course of the process, 4) the location of the area for taking the lamellar keratograft under the upper eyelid does not worsen the cosmetic appearance of the operated eye. Based on a clinical case with a severe patient, the potential of this operation is visible.Conclusion: autosclerokeratoplasty is a progressive method of surgical treatment of corneal pathologies. Since the incidence of these pathologies is high, and the risk of disability is high, the actualization of this method is most important. At the same time, all the current data on the possibilities of autosclerokeratoplasty are provided based on scientific literature and a clinical case.

Dupilumab-Associated Bilateral Conjunctival Papillomas and Corneal Perforation.

We report a unique case of significant human papillomavirus-associated conjunctival papillomas and severe corneal ulceration leading to corneal perforation in a patient treated with dupilumab for atopic dermatitis. This study is a case report and literature review of severe corneal side effects related to dupilumab. A 27-year-old man with severe atopic dermatitis and no ocular history was administered dupilumab 300 mg via subcutaneous injections every 2 weeks with an excellent response. Following the onset of treatment, the patient developed conjunctivitis, conjunctival papillomas, and dry eyes, which were initially treated with lubricating eye drops. Fourteen months after commencing dupilumab, he had a rapid onset of painful visual loss in the OD accompanied by severe bilateral conjunctival injection and was found to have a central corneal ulcer and diffuse papillomas on the palpebral and bulbar conjunctiva. Despite management with intravenous methylprednisolone and topical dexamethasone, the patient's corneal ulcer progressed to a corneal melt, resulting in perforation 2 months after diagnosis, which necessitated a corneal graft. We present the third reported case of dupilumab-associated corneal perforation and the first case to our knowledge of dupilumab-associated conjunctival papillomas. As dupilumab usage increases, awareness of these potential complications among prescribers is essential.

The mammalian Ire1 inhibitor, 4µ8C, exhibits broad anti-Aspergillus activity in vitro and in a treatment model of fungal keratitis

ObjectiveThe fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates the mRNA of the transcription factor, HacA. Previously, we demonstrated that hacA is essential for Aspergillus fumigatus virulence in a murine model of fungal keratitis (FK), suggesting the pathway could serve as a therapeutic target. Here we investigate the antifungal properties of known inhibitors of the mammalian Ire1 protein both in vitro and in a treatment model of FK.MethodsThe antifungal activity of Ire1 inhibitors was tested against conidia of several A. fumigatus isolates by a broth microdilution assay and against fungal biofilm by XTT reduction. The influence of 4μ8C on hacA mRNA splicing in A. fumigatus was assessed through gel electrophoresis and qRT-PCR of UPR regulatory genes. The toxicity and antifungal profile of 4μ8C in the cornea was assessed by applying drops to uninfected or A. fumigatus-infected corneas 3 times daily starting 4 hours post-inoculation. Corneas were evaluated daily through slit-lamp imaging and optical coherence tomography, or at endpoint through histology or fungal burden quantification via colony forming units.ResultsAmong six Ire1 inhibitors screened, the endonuclease inhibitor 4μ8C displayed the strongest antifungal profile with an apparent fungicidal action. The compound both blocked conidial germination and hyphal metabolism of A. fumigatus Af293 in the same concentration range that blocked hacA splicing and UPR gene induction (60-120 µM). Topical treatment of sham-inoculated corneas with 0.5 and 2.5 mM 4μ8C did not impact corneal clarity, but did transiently inhibit epithelialization of corneal ulcers. Relative to vehicle-treated Af293-infected corneas, treatment with 0.5 and 2.5 mM drug resulted in a 50% and >90% reduction in fungal load, respectively, the latter of which corresponded to an absence of clinical signs of infection or corneal pathology.ConclusionThe in vitro data suggest that 4μ8C displays antifungal activity against A. fumigatus through the specific inhibition of IreA. Topical application of the compound to the murine cornea can furthermore block the establishment of infection, suggesting this class of drugs can be developed as novel antifungals that improve visual outcomes in FK patients.

A comprehensive update on over the counter artificial tears.

Artificial tears play a critical role in the management of dry eye disease (DED), providing patient symptomatic relief and improving ocular surface health. Its clinical importance has driven pharmaceutical innovation in terms of its formula and ingredients. The following article is an overview of the artificial tear products on the market. The artificial tears on the market vary in terms of their active ingredients, inactive ingredients, preservatives, and formulation. The particular chemical composition of ingredients and formulation plays a clinical role in treating ocular pathology. Conversely, certain ingredients can cause more ocular damage than other ingredients. Upon review of the artificial tears on the market, the authors conclude that clinicians should consider the products' composition when designating a treatment for DED. Different artificial tear composition may benefit specific causes of DED such as evaporative, aqueous-deficient, glaucoma, ocular surface tumors, corneal ulcers, and viral conjunctivitis.

Enhancing Ex Vivo Limbal Epithelial Cell Expansion on Amniotic Membrane: A Comparative Study of Monolayer (2D) Versus Sandwich (3D) Culture Configurations.

This study compared two-dimensional (monolayer) and three-dimensional (sandwich) systems for expanding ex vivo limbal epithelial cells on amniotic membrane and evaluated the outcomes after transplantation into rabbits with experimentally induced limbal stem cell deficiency. Evaluations included markers for progenitor cells, proliferation, apoptosis, and clinical monitoring for up to 63 days. In the monolayer culture, epithelial cells derived from limbal explants were expanded on amniotic membrane as the substrate. In the sandwich culture, the cells were cultured between 2 layers of amniotic membrane. Evaluations included markers for progenitor cells, proliferation, and apoptosis, along with clinical monitoring for up to 63 days. Sandwich cultures demonstrated increased cellular proliferation and fewer progenitor cells compared with monolayer cultures. In treating limbal stem cell deficiency, the group receiving transplantation from sandwich cultures exhibited reduced neovascularization and decreased corneal ulceration compared with those treated with monolayer cultures, with similar clinical outcomes in corneal opacity. The configuration of the culture system did not affect the presence of apoptotic cells. Corneas treated with sandwich cultures showed a higher presence of progenitor cells compared with the monolayer group, suggesting a potential long-term viability advantage for these transplants. In conclusion, although the sandwich culture system enhanced cellular proliferation, it also resulted in a decrease in progenitor cells within the cultures. Nevertheless, both systems demonstrated comparable therapeutic efficacy in treating limbal stem cell deficiency, with the sandwich approach potentially offering long-term benefits because of the increased presence of progenitor cells in the transplanted cornea.

Evaluation of Fungitell (1,3)-β-D-glucan assay in tear samples for rapid diagnosis of fungal keratitis.

Fungal keratitis (FK) is a serious suppurative and ulcerative corneal infection leading to blindness and vision loss. Rapid diagnosis of FK can contribute to prompt clinical management with early recovery. The study aimed to standardize the detection of (1,3)-β-D-glucan (BDG) and establish the diagnostic cut-off concentration in tears of suspected FK patients along with non-infected controls. This prospective multicentric study was conducted between the period of August 2022 and April 2024. Samples were collected from three tertiary eye-care facilities across India. All suspected FK patients were enrolled in the study. Prior to tear collection, the eye and eyelid were gently cleansed using sterile normal saline (NS) and lint-free tissue paper. Subsequently, 50 µL of sterile NS was instilled into the eye, followed by tear sample collection after 60 s using sterile fine microtips. Tear samples were collected from the contralateral eyes of the FK patients, and those from healthy volunteers served as controls. The concentration of BDG in tears in varying dilutions was quantitatively measured using the Fungitell Assay Kit (Associates of Cape Cod, East Falmouth, Massachusetts). A total of 53 tear samples were analyzed at 1:10 and 1:20 dilutions. The receiver operating curve revealed an area under the curve (AUC) of 0.919 for the 1:10 dilution, with a cut-off value of 123 pg/mL, yielding a sensitivity of 100% and specificity of 84.85%. The corresponding Youden Index was 0.798. At the 1:20 dilution, the AUC was 0.898 with a cut-off of 84 pg/mL, achieving a sensitivity of 70% and specificity of 96.88% with a Youden Index of 0.670. Given the higher specificity at the 1:20 dilution, it was further validated in 145 tear samples. The validation cohort demonstrated a sensitivity of 95.56%, specificity of 83%, positive predictive value (PPV) of 71.67%, negative predictive value (NPV) of 97.65%, and diagnostic odds ratio of 112.4. Notably, a significantly higher BDG concentration (P < 0.0001) was observed in infected tear samples compared to controls (270.6 ± 128.5 vs 37.31 ± 31.32). Detection of BDG in tear samples is a new, non-invasive, and rapid technique showing excellent performance and can be effectively implemented for diagnosing FK in laboratories.

Neurotrophic keratitis caused by trigeminal nerve palsy secondary to a cerebellopontine angle epidermoid cyst: A rare case presentation.

Neurotrophic keratitis (NK) is a rare corneal disorder characterized by decreased corneal sensitivity and impaired corneal healing due to damage or dysfunction of the trigeminal nerve. We present a case of NK caused by trigeminal nerve palsy secondary to a cerebellopontine angle (CPA) epidermoid cyst. The patient exhibited corneal epithelial defects, persistent corneal ulceration, and decreased corneal sensation. Prompt diagnosis and management of the underlying brain lesion were crucial for successful treatment of the disease.

Global review of publicly available image datasets for the anterior segment of the eye.

This study comprehensively reviewed publicly available image datasets for the anterior segment, with a focus on cataract, refractive, and corneal surgeries. The goal was to assess characteristics of existing datasets and identify areas for improvement. PubMED and Google searches were performed using the search terms "refractive surgery," "anterior segment," "cornea," "corneal," "cataract" AND "database," with the related word of "imaging." Results of each of these searches were collated, identifying 26 publicly available anterior segment image datasets. Imaging modalities included optical coherence tomography, photography, and confocal microscopy. Most datasets were small, 80% originated in the U.S., China, or Europe. Over 50% of images were from normal eyes. Disease states represented included keratoconus, corneal ulcers, and Fuchs dystrophy. Most of the datasets were incompletely described. To promote accessibility going forward to 2030, the ESCRS Digital Health Special Interest Group will annually update a list of available image datasets for anterior segment at www.escrs.org .

Demographic and Ocular Comorbidities in Elderly Individuals with Corneal Ulcers

Demographic and Ocular Comorbidities in Elderly Individuals with Corneal Ulcers

Umbilical Cord Blood-Derived Products in Autoimmune Systemic Syndromes with Severe Dryness: A Pilot Study

Background and Objectives: Human umbilical cord blood serum (HUCBS) stands out as a potent adjunct to conventional therapies for ocular surface disorders (OSDs) caused by, among many, autoimmune systemic syndromes. By expediting ocular surface regeneration and fostering epithelial integrity, HUCBS not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This study aims to explore the efficacy of HUCBS in patients who had previously received other treatments unsuccessfully. Materials and Methods: This study was a prospective, non-comparative, interventional case series study involving 49 patients (30 females and 19 males) aged 15–82 years with severe OSDs who were unresponsive to standard treatments. The study was conducted at the San Marco Hospital, Catania, Italy. Patients were categorized into four groups based on the etiology of their severe OSDs: Group I consisted of twenty four patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; Group II comprised thirteen patients with graft-versus-host disease; Group III consisted of nine patients with corneal neurotrophic ulcers; and Group IV included three patients with Steven–Johnson syndrome. The outcomes were evaluated before and after treatment using the following assessments: OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) questionnaires, VAS (Visual Analog Scale), Slit Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time), BUT (Break-Up Time), Fluorescein Staining with Photography and Oxford Classification, The Schirmer Test, Best-Corrected Visual Acuity (BCVA), and Meibography. Results: We observed a significant improvement in the outcomes from the SANDE, VAS, and OSDI questionnaires, The Schirmer Test, BUT, BCVA, and Oxford Classification, after treatment with UCBS. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, and pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until complete healing was achieved in all cases. Conclusions: Our pilot study highlights the substantial efficacy of HUCBS in patients with systemic autoimmune diseases who have shown inadequate responses to prior treatments for dry eye. This underscores the need for further comprehensive investigations in this field.

Photoactivated chromophore for keratitis-Corneal cross-linking in dogs and cats: A retrospective study in Italy.

To evaluate the success and failure rate of photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) therapy in a single population of dogs and cats. To identify the usefulness of the PACK-CXL based on ulcer depth and establish a cutoff at which this procedure could be recommended. To analyze the influence of the different variables in corneal healing time and to report the presence of secondary endothelial damage and cataract formation. Medical records of dogs and cats with presumptive infectious keratitis which underwent accelerated epithelium-off PACK-CXL between 2016 and 2023 were reviewed and analyzed. Records for 369 animals were included, and the overall success rate for healing was 97% (range 4-74 days and no rescue procedure). The second success (re-epithelialization <30 days and no rescue procedure) rate was 86%, and a total of 40 eyes needed more than 1 month for the corneal repair. Corneal ulcers were classified in three categories based on the depth: 0%-33% (46%), 34%-66% (37.4%), and 67%-100% (16.5%). The cutoff at which PACK-CXL had a higher probability of failure was with ulcer depth >66.5%. Animals who suffered from keratomalacia and hypopyon at presentation, or were treated with topical serum or gentamicin after PACK-CXL showed an increase in epithelial healing time (EHT). Increasing age, brachycephalic conformation, keratomalacia alone, and deeper ulcers were identified as risk factors for the treatment outcome. Secondary endothelial injury or cataract formation was not noted in this study. Accelerated PACK-CXL is a non-invasive, adjunctive treatment to medical therapy, which can be used in presumed infectious keratitis with a high probability of success. However, it is important to take in consideration the patient age, skull conformation, presence of keratomalacia, and the ulcer depth.

Updates on Systemic Immunomodulation in Peripheral Ulcerative Keratitis

Peripheral ulcerative keratitis (PUK) is an inflammatory process causing thinning of the cornea, epithelial defect, and inflammatory infiltrates and is caused by several etiologies. This sight-threatening condition can indicate the presence of potentially fatal underlying systemic conditions, and, accordingly, warrants thorough investigation upon clinical presentation and immediate intervention in order to mitigate disease progression. This review aims to provide an update on the current diagnostic and management landscape for PUK, specifically with immunomodulatory methods in cases of noninfectious etiologies. A literature search was conducted to develop a nuanced, evidence-based perspective in which we present our preferred approaches. There are currently a number of viable options, following which a “stepladder” method is typically employed, where treatment methods are escalated as a result of inadequate clinical response to lower-level interventions. This method balances efficacy with the potential side effects of immunomodulatory medications. Ultimately, carefully monitored treatment regimens are needed to mitigate visual impairment in patients with PUK, and efforts must be made to achieve steroid-free remission to avoid the known side effects of long-term corticosteroid use.

Peculiarities of the regional hemodynamics in patients with mono- and bilateral herpes simplex virus stromal keratitis

Background. Herpes simplex virus keratitis (HSVK) is the main cause of blindness in the world resulted from corneal pathology. The blood circulation system of the eye plays an important role in the effective implementation of the immune response. The purpose of the study: to determine the influence of the factor of laterality of the stromal HSVK on the ocular hemodynamics and the frequency of complications. Material and methods. Primary stromal HSVK (was registered for the first time and lasted no more than 3 months) was diagnosed in 32 people (35 eyes), 205 patients (226 eyes) had recurrent stromal HSVK. Among these patients, stromal HSVK was detected both in one eye — unilateral, and in two eyes — bilateral. Complications of stromal HSVK includes: the presence of a transparent graft — in 23 eyes and its opacity — in 10 eyes, secondary glaucoma — in 6 eyes, condition after corneal ulcer — in 16 eyes. The average age of the patients (M ± SD) is 42.2 ± 15.0 years. The control group consisted of 16 healthy volunteers (32 eyes) of similar age. The standard technique of rheoophthalmogram on the ReoCom computer rheograph (Kharkiv, Ukraine) was used. The following indicators were analyzed: rheographic quotient (RQ, ‰) (pulse volumetric blood filling); α1/T (%) — the tone of the large vessels of the eye; velocity of blood filling V (Ohm/s). Results. Patients with stromal HSVK had mainly monolateral eye lesion — 89.8 %, and bilateral lesion was present in 10.2 % of cases. There were no significant differences in the frequency of laterality between primary and recurrent stromal HSVK. In case of recurrence of complicated unilateral and bilateral stromal HSVK, the volumetric pulse blood filling was 17.6 and 30.3 % lower, respectively, than in uncomplicated course, which determines the insufficiency of blood supply to the eye. The rate of blood filling in complicated stromal HSVK was lower than in uncomplicated one by 23 %. At the recurrence of bilateral stromal HSVK, the RQ was higher by 26.4 %, and the rate of blood filling was higher by 36.3 % compared to unilateral one. There were no differences in remission. The tone of the large vessels of the eye with bilateral stromal HSVK is 14 % lower than with unilateral course. Conclusions. In case of recurrent stromal HSVK, the volume pulse blood filling of the eye and its velocity are higher, and the vascular tone is lower than in case of unilateral one, both uncomplicated and complicated. It is assumed that such a significant activation of the ocular hemodynamics is compensatory and contributes to a greater local immune response and improvement of trophism.

Letter Regarding: Validation of the C-DU(KE) Calculator as a Predictor of Outcomes in Patients Enrolled in Steroids for Corneal Ulcer and Mycotic Ulcer Treatment Trials

Letter Regarding: Validation of the C-DU(KE) Calculator as a Predictor of Outcomes in Patients Enrolled in Steroids for Corneal Ulcer and Mycotic Ulcer Treatment Trials

A Study of Clinico-Microbiological Profile and Treatment Outcomes of Infectious Keratitis.

Background Infectious keratitis (IK) is one of the major causes of corneal blindness in developing and developed nations.Numerous infections, including bacterial, fungal, viral, and protozoa, have been linked to IK. Corneal perforations can happen as one of the complications of IK. In this study, we aim to determine the clinical and microbiological profile and to studythe treatment outcomes of IK. Material and methods It is a prospective, observational, and experimental study conducted in a tertiary care hospital and research centerin Western Maharashtra, India, from September 2022 to June 2024. The sample size was 107 patients with IK. All patients were above 15 years of age, and all cases of microbial keratitis were within the inclusion criteria. Patients less than 15 years of age, patients with any other associated corneal pathology, healed cases of infectious keratitis, peripheral ulcerative keratitis, patients not willing to participate in the study, or not giving consent were excluded. Patients were examined thoroughly, and corneal scraping samples were collected and sent for microbiological examination. Appropriate treatment was provided through medical or surgical management, and treatment outcomes were evaluated during frequent follow-up visits. Results In our study, the majority of patients originated from rural areas, with most being over 60 years of age. Diabetes mellitus was seen in 24.3%, and a history of ocular trauma was present in 48.5% of patients. Staphylococcus epidermidis (3.74%) was the most common organism seen on gram staining, followed by Staphylococcus aureus (2.8%). Pseudomonas aeruginosa was the only gram-negative organism seen. The number of patients who had fungal isolates positive on culture was 57%, 12.1% had bacterial, and 30% had no growth of microorganisms. Fusarium species were seen in 39.2% of culture isolates, followed by Aspergillus flavus and Niger in 7.47% each. In 96% of medically managed patients, ulcers healed within two months. All ulcers with severe and moderate depth required therapeutic penetrating keratoplasty. A graft was in place in 95.2% after therapeutic penetrating keratoplasty, while one patient had graft rejection, and in one patient, endophthalmitis was seen. Conclusion Staphylococcus epidermidiswas the most common bacterial agent isolated on gram staining, and Pseudomonas aeruginosa was the only gram-negative bacillus isolated on gram staining. Fungal isolates were the most common isolates observed on culture, seen in more than half of the IK patients in our study. The majority of patientswho underwent medical management had ulcers healed in two months. The majority of the patients who underwent surgical management had fungal isolates positive.We recommend further research to be conducted in a generalized population, including urban settings, to understand the risk factors, microbiological profile, and treatment outcomes for IK.

Sublimbal orbital fat transposition in neurotrophic keratopathy: a case series

Neurotrophic keratopathy is a progressive condition resulting from corneal denervation, leading to the development and persistence of corneal ulcers. Among the pathogenetic treatment methods there are corneal neurotization, a technically challenging approach associated with a prolonged rehabilitation period, and the usage of recombinant human nerve growth factor (cenegermin), which is practically inaccessible due to its high cost and lack of registration in Russian Federation. We propose a technique of orbital fat transposition to the sclerocorneal pocket for the treatment of persistent ulcers associated with neurotrophic keratopathy. This method is based on neuronal embryology of orbital adipose tissue, as well as the abundance of neurotrophic factors and stem cells. This method was applied to three patients with different etiologies of neurotrophic keratopathy, reaching the observation endpoint in two months after the operation. Visual acuity was ranging from 0.005 to 0.01. All patients received standard therapy for 1–2 months without significant improvement. Surgery was then performed using the proposed technique, which involves repositioning the medial and central orbital fat pads into the sclerocorneal pocket. In the postoperative period, partial epithelialization was observed in all patients during the first week, followed by complete healing and scar formation. The maximum visual acuity in 2 months ranged from 0.06 to 0.3.

Ocular Lesions in Birds of Prey in Portugal: A Retrospective Study

In wildlife rehabilitation centers, thousands of animals are treated annually, with a substantial proportion being birds of prey. Since vision is essential for the survival of these species, this study focused on investigating the causes of ocular injuries in raptors admitted to four rehabilitation centers across mainland Portugal from 2017 to 2021. Of the 2207 birds admitted during this period, 156 (7%) presented ocular injuries. Hyphema (28.2%) and corneal ulcers (20.5%) were the most prevalent injuries, often occurring together or alongside lens luxation. Nocturnal raptors showed a higher prevalence of these injuries (76.9%) compared to diurnal raptors (23.1%). A significant association was found between ocular injuries and causes of admission, particularly with ocular hemorrhages and multiple injuries in the eye. Despite the severity of the ocular injuries, the release rate remained relatively high at 51%, underscoring the critical role of comprehensive ocular examinations and vision assessments in guiding treatment decisions and discharge decisions. This study highlights the need for further research with larger samples to better understand the impact of ocular injuries on the rehabilitation success of wild birds in Portugal.

Umbilical Cord Blood Platelet Lysate Eyedrops for the Treatment of Severe Ocular Surface Disorders in Graft vs. Host Disease Patients: Clinical Study

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p &lt; 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD.

Novel ophthalmic hyaluronic acid-hydrogel with curcumin nanoparticles for enhanced healing of ulcerative keratitis in rabbit model

Corneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with β-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with β-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with β-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage.

Evaluation of a new classification system for measuring the progression of ocular cystinosis: an analysis of 64 patients

AimsTo analyse the correlation between the physician categories defined by the 3C classification (crystal-complication-compliance) and the ocular manifestations of nephropathic cystinosis.MethodsThe last visit data of 64 patients aged between 2...