Corneal Ulcer Research Articles

Experience of using autologous cornea for deep and penetrating keratoplasty in dogs and cats

This paper presents a generalized experience in the treatment of deep corneal ulcers, descemetoceles and perforated corneal ulcers in which keratoplasty was used using autologous cornea. Deep corneal ulcers are characterized by an acute inflammatory process and the risk of developing many complications leading to loss of vision. Conservative treatment of such pathologies takes a long time and is not always successful. Keratoplasty for corneal transplantation is considered an effective method. The outcome of the operation depends on the transplanted material and postoperative treatment tactics. The work conducted a study on the effectiveness of using autologous cornea in 32 animals with subsequent inclusion of a regenerative drug in the treatment regimen. The authors describe the clinical picture, the surgical technique, and provide the results of dynamic observation of animals. Based on the results of clinical observations, it was established that the use of autologous cornea for deep corneal ulcers can be an effective treatment method. In none of the 32 cases examined, rejection was recorded, while the morphofunctional characteristics of the cornea were preserved. Drug maintenance therapy, including a regenerative drug, showed good results in the postoperative period. The use of a regenerative drug accelerated the healing process and made it possible to maintain the transparency of the cornea and its curvature.

Analysis of the potential of the homeopathic eye drops Marine Cineraria 4CH to induce cell migration

The ocular surface comprises diverse components that collaborate to maintain homeostasis, and any change can be termed an ocular surface disorder. One frequently observed change is the development of corneal ulcers, a primary contributor to visual impairment. Cineraria maritima is a botanical species renowned for its therapeutic application in managing diagnosed cataracts and other eye-related ailments. This study evaluated the effect of the homeopathic eye drops containing Cineraria maritima using cell viability assessments, a scratch experiment, and the quantification of IL-8 levels. The in vitro tests revealed the absence of any cytotoxic effects associated with the eye drops, thus demonstrating their safety for use. Furthermore, these eye drops exhibited the capacity to enhance the percentage of scratch closure. The treated group had an average closed area percentage of 57%, while the control group exhibited only 41% area closure, indicating the potential efficacy of eye drops in managing ocular disorders. Finally, IL-8 levels were measured following the induction of an inflammatory response by LPS and subsequent treatment with the eye drops. The outcomes indicate a decrease in the levels of this cytokine in the treated group. Such findings assure the safety and effectiveness of Cineraria maritima 4CH homeopathic eye drops, suggesting a potential avenue for their application to treat corneal ulcers.

Challenging course of endophthalmitis with corneal ulcer following cataract surgery: successful management and visual rehabilitation

Challenging course of endophthalmitis with corneal ulcer following cataract surgery: successful management and visual rehabilitation

Actual aspects of treatment and prevention of infectious bovine keratoconjunctivitis

Infectious bovine keratoconjunctivitis is a bacterial eye disease. The disease is characterized by inflammation of the conjunctiva, corneal ulceration and excessive lacrimation. Although this disease does not lead to the death of animals, its economic importance is enormous, since it leads to a decrease in livestock weight gain and a reduction in dairy productivity. The main etiological role in IBK belongs to Moraxella spp. (including in associations with Staphylococcus spp., Streptococcus spp., Pseudomonas aeruginosa, E. coli, Proteus). The use of traditional treatment methods, such as the use of antibacterial chemicals, for Moraxella infection may be ineffective due to the factors of resistance and immunity of these bacteria. The development of a vaccine can be expensive and time-consuming, due to the external localization of the infection; it will be difficult to achieve a protective effect. New strategies for the treatment and prevention of bacterial infection open up prospects for the use of bacteriophages. Due to the growing antibiotic resistance of circulating bacterial pathogens and to increase the effectiveness of therapeutic and preventive measures in IBK, the development of phage therapy is relevant. Fundamental studies of biological properties and exploratory studies of virulent active bacteriophages to zoopathogenic Moraxelles are an urgent problem.

Bowman's layer transplantation—A new hope for regaining of correct ocular surface

Aims/Purpose: To present a novel surgical technique of selective Bowman's layer transplantation as well as results of the surgery in patients with neurotrophic corneal ulcers.Methods: 3 eyes from 3 patients with neurotrophic corneal ulcers who underwent corneal grafting with Bowman's layer. Pre‐ and postoperative analyses of the anterior segment of the eye were based on optical coherence tomography and slit lamp assessment.Results: Postoperatively a gradual corneal stroma restoration and fast corneal epithelialisation were noticed.Conclusions: Based on our observations, stiff and firm structure of Bowman's layer is supposed to strengthen corneal surface and maintain its shape. It acts also as an anti‐pathogen and anti‐toxin corneal barrier. Application of this acellular corneal layer transplantation to cover trophic corneal ulcers is an interesting, modern and crucial method of neurotrophic keratitis treatment.Reference1. Hsu HY, Modi D. Etiologies, quantitative hypoesthesia, and clinical outcomes of neurotrophic keratopathy. Eye Contact Lens 2015;41(5):314–7.2. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol 2014;8:571–9.3. Mantelli F, Mauris J, Argüeso P. The ocular surface epithelial barrier and other mechanisms of mucosal protection: from allergy to infectious diseases. Curr Opin Allergy Clin Immunol. 2013 Oct;13(5): 563–8.4. Wilson SE. Bowman's layer in the cornea‐ structure and function and regeneration. Exp Eye Res 2020 Jun;195:108033.5. Lagali N, Germundsson J, Fagerholm P. The Role of Bowman's Layer in Corneal Regeneration after Phototherapeutic Keratectomy: A Prospective Study Using In Vivo Confocal Microscopy. Invest Ophthalmol Vis Sc. 2009 Sep;50(9):4192–8.

Graves Eye Disease Medical and Surgical Management: A Review

Graves’ disease (GD) is the most frequent cause of hyperthyroidism, where iodine levels are abundant. One of the extrathyroidal symptoms is Graves’ ophthalmopathy (GO) which presents with ophthalmic symptoms that can range from minor (e.g., dry eye) to sight-threatening (e.g., corneal ulceration and compressive optic neuropathy) features. About 79% of Graves’ disease cases can be attributed to genetic predispositions, while the remaining 21% are due to environmental factors. Acute stress, active or passive smoking, and past radioactive iodine therapy have all been linked to the development or aggravation of thyroid eye disease (TED). The devastating effects of GO or TED might include diplopia, ocular hypertension, optic nerve degeneration, and glaucoma. A low basal serum Thyroid Stimulating hormone (TSH) level has the highest sensitivity and specificity for diagnosing hyperthyroidism. Moreover, the appearance of Thyroid Stimulating hormone receptors (TSHR) autoantibodies (TRAbs) is presumed to be highly specific for the diagnosis of Graves’ disease. Imaging studies of the orbit that use ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), for example, can confirm the diagnosis of TED. In order to treat Graves’s eye disease optimally, a multidisciplinary approach must be applied involving primary care physicians, ophthalmologists, internists and endocrinologists. Therefore, it is essential to restore the euthyroid state and this can be obtained by either antithyroid medications, radioactive iodine or surgical thyroidectomy. Treatment of GO ranges from supportive treatment (lubricants and moisturizer drops), to medical intervention, preferably corticosteroid, and variable surgical interventions. Key words: Graves’ disease, Medical and surgical management

Non infectious ocular surface inflammation: Paediatric GVHD

Although ocular findings and treatment for GVHD are described in adult patients, the literature describing this condition in paediatric patients is relatively few. In children, detection of symptoms and diagnosis of ophthalmic findings are more difficult than in adults, as history taking, clinical examination and diagnostic tests such as fluorescein staining or Schirmer tests are difficult to perform due to limited cooperation. Also patients cannot specify their complaints and symptoms especially in younger age group. Follow‐up and frequent ophthalmic evaluation are important in diagnosis and management of children who had bone marrow transplantation. Even though ophthalmic findings are common in children, usually milder than adults but timely diagnosis and management are very important to decrease secondary eye complications such as corneal ulcers and vision loss and also to improve quality of life.Graft‐versus‐host disease (GVHD) is a major complication of bone marrow transplantation that is performed for haematological malignancies and diseases and seen in 50–70% of cases. It is a complex clinical disease with many organ and system involvement. Acute form is seen in the first 3 months after transplantation, systemic manifestation mainly include hepatitis and skin involvement and chronic form is mostly seen after acute GVHD. Ocular manifestations can be classified as acute and chronic and also as anterior and posterior. Most common ocular finding is dry eye with corneal involvement and seen in 40–90% of patients with chronic GVHD. Corneal vascularization, keratitis and even perforation can be seen. Conservative treatment with topical steroids, autologous serum, lubricant eye drops and ointments should be integrated with topical cyclosporine‐A that might be an effective and safe treatment option in dry eye related to chronic GVHD.

Cornea on fire: PACK‐CXL in the treatment of infectious keratitis

Infectious keratitis is a severe eye condition that can cause permanent vision loss if not treated promptly. The current standard of care for this condition involves the use of broad‐spectrum topical antibiotic drops. However, researchers have explored photoactivated chromophore for collagen cross‐linking (PACK‐CXL) as a potential treatment option for infectious keratitis. Studies have shown that PACK‐CXL can improve the healing process in bacterial keratitis and prevent corneal melting caused by bacterial enzymatic degradation.When activated by UV light, riboflavin, the photosensitizer used in PACK‐CXL, induces changes in collagen properties, leading to a hardening and strengthening effect on the corneal stroma. However, individuals with corneal ulcers may experience greater penetration of UV light due to the compromised integrity of the cornea, which could cause endothelial cell loss and impair corneal function.The purpose of this presentation is to provide a summary of the evidence on the comparative effectiveness and safety of PACK‐CXL with or without standard therapy versus standard therapy alone for the treatment of bacterial keratitis. The latest randomized controlled trials (RCTs) will be reviewed, and their findings regarding the efficacy and safety of PACK‐CXL in treating infectious keratitis will be discussed, as well as a comparison with standard antibiotic therapy alone. Ultimately, this talk aims to inform evidence‐based recommendations for the treatment of infectious keratitis and provide clinicians with the most up‐to‐date information to make informed treatment decisions.

Периферические язвы роговицы в ассоциации с ревматической патологией

Background: peripheral ulcerative keratitis (PUK) is a polyetiological disease. The pathogenesis of PUK is attributed to a combination of factors, including the anatomy of the peripheral cornea, the activation of autoimmune reactions, and the corneal destruction caused by autoan- tibodies and matrix metalloproteinases. Aim: to describe the clinical symptoms of PUK, its association with rheumatic diseases (RD), its course, and the efficacy of treatment options. Patients and Methods: а total of 32 patients (9 men and 23 women, mean age 59.3±9.4 years) with PUK associated with RD were under surveillance. The diagnosis was established based on the results of eye examinations, tear production test, and multidisciplinary examination. Treatment was performed in an outpatient or inpatient setting based on the severity of corneal lesions. Results: the most common association between PUK and RD was established with rheumatoid arthritis (56.2%). Clinical hallmarks of PUK included mild infiltration and perifocal corneal edema, accompanied by the appearance of an oval or sickle-shaped epithelial and stromal defect 2–4 mm from the limbus. Additionally, rapid corneal lysis and perforation (18.7%) and association with perilimbal vasculitis and scleritis (31.2%) were observed. Bilateral corneal lesions were observed in 56.2%. Tear production, as measured by Schirmer's test, was 6±2 mm, while tear film stability was 2±1 mm. Conservative management was found to be effective in 59.4% (outpatient treatment in 40.6% and inpatient treatment in 18.7%). Surgical interventions were performed for emergent indications, including tectonic keratoplasty (21.9%) and deep anterior lamellar keratoplasty (15.6%). Conclusion: PUK represents a severe clinical manifestation of visual disorders in RD. Treatment for PUK involves local and systemic steroids in the acute period, basic immunosup-pressive therapy, and, when necessary, keratoplasty. Systemic rheumatological therapy, regular use of tear substitutes and reparative preparations are prescribed to prevent recurrences. KEYWORDS: keratitis, corneal ulcer, limbus, autoimmune diseases, rheumatoid arthritis, keratoplasty. FOR CITATION: Drozdova E.A. Peripheral corneal ulcers in association with rheumatic diseases. Russian Journal of Clinical Ophthalmology. 2024;24(2):88–93 (in Russ.). DOI: 10.32364/2311-7729-2024-24-2-8.

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

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

Specific corneal epithelial cell markers in congenital aniridia

Congenital aniridia is a rare panocular disease in which almost all structures of the eye are affected. The observed corneal abnormalities are called aniridia‐associated keratopathy (AAK). AAK is characterized by progressive limbal stem cell deficiency (LSCD), epithelial thinning and erosions, corneal ulceration, vascularization, inflammation and pannus formation. Although in some aspects AAK resembles other types of LSCD, through its specific genetic origin, alterations in corneal epithelial cell gene expression differ from other types of corneal diseases. Primary limbal epithelial cells of aniridia subjects lack expression of KRT3 and KRT12 mRNA and protein, and DSG1, ADH7, FABP5, CRABP2, SPINK7 and ALDH1A1 mRNA expression is decreased in these cells. However, miRNA 138‐5p expression is upregulated. This epithelial behaviour can also be mimicked using an siRNA based aniridia primary limbal epithelial cell model.

Corneal opacities in children

The corneal opacities in childhood could be either, congenital or acquired. The congenital could either localized/non‐systemic disease, like the congenital hereditary endothelial dystrophy, posterior polymorphous corneal dystrophy, congenital hereditary stromal dystrophy, peters anomaly, congenital anterior staphyloma, sclerocornea, cornea plana, cornea tumours, epibulbar dermoid, or related to systemic/metabolic Disorders like mucopolysaccharidoses, cystinosis, tyrosinemia, schnyder crystalline dystrophy, fetal alcohol syndrome. The acquired corneal opacities could be either traumatic, like traumatic breaks in descemet membrane, corneal blood staining, corneal keloids, or non traumatic like keratoconus, posterior corneal depression, keratoglobus, congenital or infantile glaucoma, Corneal ulcers, Familial dysautonomia (Riley‐Day syndrome), Stevens‐Johnson syndrome and toxic epidermal necrolysis. We will discuss these cases, their clinical picture, work up and management.

A Case of Corneal Melt and Perforation Associated with Rheumatoid Arthritis Managed by Corneal Patch Graft

Corneal melt is a rare yet severe complication of Peripheral Ulcerative Keratitis (PUK), observed in patients with Rheumatoid Arthritis (RA). The mortality rate associated with corneal melt is high, warranting aggressive treatment. A 50-year-old female, a known case of RA for 20 years, presented with complaints of blurred vision, watering, irritation, and photophobia in both eyes for the last year, with worsening symptoms in the Right Eye (RE) for the past 15 days. She was diagnosed elsewhere in a private hospital with RE corneal melt and perforation and inferior corneal thinning in the Left Eye (LE), with an ulcer defect. She underwent corneal perforation suturing in the RE before reaching the present facility. On examination, a sutured corneal perforation was present in the RE, and corneal thinning and melt were seen para-centrally and inferiorly in the LE. Surgical treatment with RE corneal patch graft repair was performed. The patient was given oral methotrexate and prednisolone for aggressive systemic control of RA and to ensure the survival of the patch graft. The vision in the RE improved following the procedure, maintaining the tectonic integrity of the cornea. On follow-up, aleucomatous opacity was noted in the RE patch graft tissue. Corneal thinning in the LE was treated topically with artificial tears and antibiotic eyedrops, which eventually healed, forming macular corneal opacity. Overall, corneal patch graft repair enabled the maintenance of tectonic support and corneal integrity, as well as vision improvement in the patient with RA presenting with the complication of corneal melt and perforation.

Medical and surgical management of neurotrophic keratopathy

Neurotrophic Keratopathy (NK) is not a specific disease entity but a consequence of several conditions with varied aetiopathogenesis, of which a loss or reduction in corneal sensitivity is the hallmark. NK is clinically graded as Mild (stage1), Moderate (stage 2) and Severe (stage 3). The grading helps in understanding severity and planning treatment. Management can be considered in two parts. The first is the management of the underlying condition when active, for example herpes virus keratitis, bacterial ulcers and immune mediated ulcerative keratitis; and the second part, which deals with treatment of the non‐healing epithelial defect, stromal melting with or without vascularization and perforation that remains due to epithelial, stromal and corneal nerve pathology.Management of mild and moderate NK begins with the identification and elimination of any obvious underlying cause such as neuroleptic, antipsychotic, antihistamine and other systemic medications, preservatives in long term topical medications; and treatment of concurrent ocular surface infection. Tear substitutes and anti‐inflammatory agents both steroids and specific immunosuppressors like cyclosporin and lifitegrast should be used early. Antibiotics can be used prophylactically or to treat subclinical or overt infection. Medication with preservatives should be avoided. Prevention of progression to severe (stage 3) NK can be achieved with antiproteases such as citrate, tetracyclines and macrolides. Substrate re‐generating agents like Cacicol and promoters of epithelial regeneration like co‐enzyme Q10 target aspects of the underlying pathology. The introduction of recombinant human nerve growth factor (rh)NGF (Cenegermin/Oxervate) has provided specific therapy that addresses the basic defect related to corneal nerves. Insulin drops are proving to be useful and amniotic membrane extracts/amniotic fluid has also been tried. Autologous and pooled allo serum or plasma drops, which provide a variety of known and unknown factors have also proved useful but may at times aggravate the condition. Usually a combination of two or more of the above are required but rhNGF and insulin hold considerable promise for long term remission.Medical treatment is often augmented with non‐surgical interventions such as bandage contact lens, padding, punctal plugs, botulinum toxin, frost suture and glue. These are primarily designed to deal with exposure, dry eyes and reduce the abrasive effect of lid blinks, to promote healing. Useful surgical procedures include tarsorrhaphy, amniotic and conjunctival grafts, penetrating and lamellar keratoplasty and limbal stem cell transplants. Surgical interventions are designed to augment effects of the non‐surgical interventions, reduce scarring, deal with complications and restore sight. A key principle is that wound healing after any form of surgery or transplant, is poor if the corneal sensations remain impaired or absent.

<b>Bilateral phacoemulsification and intraocular lens implantation in a pet rabbit with cataracts</b>

<b>Background:</b> The occurrence of cataracts in rabbits is a common reason for consultation in veterinary ophthalmology. <b>Case Description: </b> A 6-year-old female Lop rabbit (Oryctolagus cuniculus) was referred with a 3-month history of bilateral cataracts. The owner noted that the rabbit was frequently bumping into obstacles. Physical examination was unremarkable. Routine hemogram and biochemistry panel were within usual values, and Encephalitozoon cuniculi was not detected by serology. A complete ophthalmological examination revealed bilateral hypermature cataracts causing total blindness. Bilateral tonometry showed normal intraocular pressures. Electroretinography under general anesthesia revealed strong photoreceptor responses for each eye, and ocular ultrasound was normal except for bilateral hypermature cataracts. Following electroretinography, during the same anesthesia session, conventional phacoemulsification followed by acrylic intraocular lens (IOL; +58D) implantation was performed uneventfully in both eyes. Follow-up examinations were carried out for one year. Except for immediate post-operative bilateral corneal ulcers that were quickly cured with medical treatment, no other post-operative complications were observed. The one-year follow-up examination revealed centered IOLs without posterior capsular opacity, enabling the observation of normal fundus in both eyes. The owner confirmed the rabbit had normal autonomy and moved with accuracy, as observed during follow-up visits and on videos provided by the owner. <b>Conclusion: </b> To our knowledge, this is the first described case of successful bilateral phacoemulsification and bilateral intraocular lens implantation with prior electroretinographic evaluation of the retinal function in a pet rabbit with cataracts.

Herpetic keratouveitis: A three year follow‐up case

Aims/Purpose: Herpetic keratouveitis1 is a common presentation to Eye Casualty but due to the broad spectrum of manifestations that it can present with, it is an easy diagnosis to miss. The aim of this report is to create awareness among ophthalmologists of how this disease can present, appropriate clues to the diagnosis as well as how it should be managed.Methods: A 76 year old male presented to the eye emergency department with a 1 week history of significant visual deterioration (6/90 pinhole), redness and photophobia in his left eye. He was initially treated 6 weeks prior with a course of tapering steroid drops for presumed acute anterior uveitis which led to an initial improvement in symptoms, followed by a sudden worsening of symptoms. Ocular examination revealed a 9 mm × 8 mm central corneal ulcer with a satellite lesion superonasally, Descemet folds, reduced corneal sensation with mild anterior chamber inflammation and no posterior segment pathology. Corneal scrapes as well as PCR was sent for culture and sensitivity.Results: PCR revealed a positive result for herpes simplex virus and the patient showed significant improvement with oral acyclovir, topical gancyclovir ointment and topical steroid drops. In the 3 years following the initial presentation, the patient has had 3 further episodes of left herpetic keratouveitis and has now been put on lifelong maintenance dose oral acyclovir and FML drops.Conclusions: We report this case to highlight the key clinical features compatible with herpetic keratouveitis. This disease can be chronic and should be considered in any patient presenting with chronic anterior uveitis not improving with steroid drops. PCR remains the gold‐standard for diagnosis however this is not always positive and clinical diagnosis remains key.Reference1. Cunningham E.T. Diagnosing and treating herpetic anterior uveitis. Ophthalmology 2000; 107(12: 2129–30. doi:10.1016/s0161‐6420(00)00287‐6.

Efficient role of VITEK systems in rapid identification of different corneal ulcer infectious microorganisms during an updated survey in Egypt

Efficient role of VITEK systems in rapid identification of different corneal ulcer infectious microorganisms during an updated survey in Egypt

Management of corneal ulcer with hypopyon: A case report and review of current guidelines

Management of corneal ulcer with hypopyon: A case report and review of current guidelines

Comparative study between topical insulin, autologous serum, and honey-based eye drops as adjunctive treatment in resistant corneal ulcer

Background Resistant keratitis is a difficult situation faced every day in ophthalmology clinics. Resistance to healing may be attributed to many factors. Many adjunctive agents are widely used in a trial to accelerate healing and to prevent resistance to eliminate the chance of development of disabling complications. Purpose The aim of this study was to compare the effectiveness of topical insulin, autologous serum, and honey-based eye drops as adjunctive therapies in resistant corneal ulcers. Patients and methods This prospective study investigated 45 eyes of infected keratitis not responding to culture-based medical treatment for 2 weeks. The eyes were divided into three groups each of 15 eyes. The insulin group was treated with topical insulin drops, the serum group with autologous serum drops, and the honey group with honey-based drops. Culture-based medical treatment was also continued in the three groups till complete healing was achieved. The results of the three groups were compared regarding the time needed for healing and best-corrected visual acuity outcome. Results Best-corrected visual acuity improved by one or more lines in 11 (73.33%) cases in the insulin group, in 10 (66.67%) cases in the serum group, and in nine (60%) cases in the honey group, with no statistically significant difference (χ 2=1.525, P=0.822). Healing occurred in 14–28 days in 12 (80%) cases in the insulin group, in 13 (86.67%) cases in the serum group, and in 10 (66.67%) cases in the honey group, with no statistically significant difference (χ 2=1.8, P=0.407). The remaining cases in each group required amniotic membrane transplantation due to thinning. Conclusion The effects of topical insulin, autologous serum, and honey-based eye drops, when used as adjunctive methods added to the culture-based medical therapy in the management of resistant corneal ulcers, were comparable. Autologous serum gave slightly higher effect than topical insulin and honey-based eye drops but the difference was statistically insignificant.

Corneal complications of ocular GvHD

Corneal fluorescein staining is one of the tests recommended to diagnose and grade ocular graft versus host disease (GvHD) according to the International Chronic Ocular GvHD Consensus Group. Despite superficial punctate keratopathy is the most common corneal manifestation, patients with more severe stages may develop corneal neovascularization, sterile corneal ulceration and even perforation. Previous in vivo confocal microscopy (IVCM) studies reported significant microstructural changes in the cornea of patients with ocular GvHD, including a higher density of dendritic cells and globular immune cells, a network of hyper‐reflective activated keratocytes, and a lower density and higher tortuosity of sub‐basal corneal nerves. Dendritic cells act as antigen‐presenting cells, and play a key role in ocular surface immune homeostasis. Thus, their increased density may be indicative of immune activation and inflammation of the ocular surface in patients with ocular GvHD. Interestingly, Kheirkhah et al. reported higher dendritic cell density in patients with DED owing to systemic immune disease (i.e., Sjögren syndrome and ocular GvHD) compared to patients with DED of other origins. Recently, our group employed a fully automated IVCM analysis system to compare corneal sub‐basal nerve plexus in patients with DED owing to both ocular GvHD and Sjögren syndrome and in healthy control subjects. Although overall patients with DED showed lower density of nerve fibres and branches, shorter nerve fibres and higher fibre width compared to healthy controls, no significant difference was observed between patients with ocular GvHD and Sjögren syndrome for all IVCM metrics. In agreement with this observation, other studies reported no significant difference of IVCM parameters in DED patients with and without ocular GvHD after adjusting for clinical severity of dry eye. This suggests that the ocular surface changes observed by IVCM in ocular GvHD may be possibly reflective of the local disease severity rather than the underlying systemic process.