A Patient-Centered Approach to Vernal Keratoconjunctivitis (VKC): A Podcast.

Vernal keratoconjunctivitis (VKC) is a rare yet severe form of allergic conjunctivitis predominantly affecting children, mainly boys, with a global prevalence and a higher incidence in certain geographical regions. The disease is characterized by seasonal exacerbations. VKC presents with ocular surface inflammation leading to various distressing symptoms such as itching, redness, mucous discharge, and pain. The disease primarily manifests bilaterally, though it may initially appear unilaterally. If left untreated, VKC can result in corneal complications, including shield ulcers and vision impairment, affecting daily activities and psychosocial well-being, especially in children. The diagnosis of VKC involves identifying key clinical findings on the ocular surface such as Tranta dots, giant papillae, or shield ulcers. Management follows a stepwise approach, including anti-allergic eye drops, steroid eye drops, and topical medications like cyclosporine, which may take up to 3 months to show efficacy. Allergic sensitization, often to inhaled allergens like pollen and house dust mites, is associated with VKC in half of the cases. Understanding and managing these allergies through measures such as avoidance, sensitization control, and co-treatment of associated conditions like asthma and rhinoconjunctivitis are essential in VKC management. Atopic keratoconjunctivitis (AKC), a related condition associated with atopic dermatitis and asthma, shares similarities with VKC but typically affects young adults. However, there is an observed spectrum between the two diseases, indicating similar treatment strategies for both. VKC treatment requires a patient-centered approach, involving informed and supported parents, considering economic factors due to costly eye drops, and ensuring accessibility and practicality of treatment, especially in children. A multidisciplinary team collaboration, including ophthalmologists, pediatricians, and dermatologists, optimizes patient care. The rewarding aspect of VKC treatment lies in witnessing children regain their quality of life, overcome vision challenges, and thrive in their daily activities. In conclusion, understanding VKC, its associated allergies, and employing a comprehensive, patient-centered approach are crucial in managing this challenging condition, particularly in children, to enhance their vision and overall well-being.

Tear film proteome changes following Tobradex® therapy in anterior blepharitis.

PURPOSE: The management of blepharitis continues to challenge clinicians due to the poorly understood aetiology of the condition. We recently identified the family of intracellular plakin proteins as essential driving forces underlying anterior blepharitis. A large-scale protein analysis was used to study if a topical dexamethasone/tobramycin solution could be used to reverse the expression of plakin proteins. METHODS: Tear film samples from treatment naïve patients with anterior blepharitis (n = 15) were collected with Schirmer filtration paper. A subgroup of the patients (n = 10) received treatment with a dexamethasone/tobramycin 1 + 3 mg/mL ophthalmic suspension (Tobradex® ) for 3 weeks and collection of tear film samples was repeated. The samples were analysed with label-free quantification nano liquid chromatography-tandem mass spectrometry requiring quantification in at least 70% of the samples in each group. Proteins were considered differentially expressed if p < 0.05. RESULTS: Following Tobradex® intervention, 27 proteins were upregulated while 61 proteins were downregulated. Regulated proteins after Tobradex® treatment were involved in intermediate filament cytoskeleton organization including downregulation of the plakin proteins envoplakin, epiplakin and periplakin. Plectin, a protein of the plakin family, remained unchanged after Tobradex® therapy. Tobradex® treatment resulted in the regulation of proteins involved in translation including a cluster of downregulated ribosomal proteins. Tobradex® intervention was associated with the regulation of proteins involved in fructose metabolism and glycolytic processes including fructose-1.6-bisphosphatase 1, fructose-bisphosphate aldolases A and B, pyruvate kinase PKM and transketolase. Ig lambda chain V-I region, prominin-1, and protein Niban were upregulated after Tobradex® treatment. CONCLUSIONS: Tobradex treatment reversed the expression of plakin proteins in anterior blepharitis. Topical solutions which inhibit the expression of plakin proteins may have the potential to restore the ocular surface integrity in anterior blepharitis and should be explored further.

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulated. The largest change was observed in cystatin-SN, which was downregulated in MGD and correlated negatively with tear meniscus height. The downregulation of cystatin-SN was confirmed with targeted mass spectrometry by single reaction monitoring (SRM). Eighteen immunoglobulin components involved in B cell activation, phagocytosis, and complement activation were downregulated in MGD including Ig alpha-1 chain C region, immunoglobulin J chain, immunoglobulin heavy variable 3-15, and Ig mu chain C region. The changes in cystatin-SN and immunoglobulin chains are likely to result from the inflammatory changes related to tear film evaporation, and future studies may assess their association with the meibum quality.

Surgical Treatment of Corneal Shield Ulcer in Vernal Keratoconjunctivitis: A Systematic Review.

BACKGROUND: Vernal keratoconjunctivitis (VKC) severely affects the quality of life of affected patients. The development of a shield ulcer is considered one of the most severe late-stage complications, which when untreated leads to irreversible vision loss. In this systematic review, we outlined the results of surgical treatments of corneal shield ulcers in VKC. METHODS: We searched 12 literature databases on 3 April 2023 for studies of patients with VKC in which shield ulcers were treated by any surgical treatment. Treatment results were reviewed qualitatively. Assessments of the risk of bias of individual studies were made using the Clinical Appraisal Skills Programme. RESULTS: Ten studies with 398 patients with VKC were eligible for the qualitative review. Two categories of surgical approaches were described: supratarsal corticosteroid injection and debridement with or without amniotic membrane transplantation. Almost all patients experienced resolution or improvement of their shield ulcers, regardless of treatment modality. Time to healing was faster with surgical debridement. A small proportion experienced recurrence and side effects. CONCLUSIONS: Surgical treatment for shield ulcers in VKC seems highly effective, but careful post-operative treatment and follow-ups are necessary due to the risk of recurrence and potential side effects.

Anterior blepharitis is associated with elevated plectin levels consistent with a pronounced intracellular response.

PURPOSE: Anterior blepharitis is a frequent ocular condition which may result in severe ocular surface disease. In this study, advanced proteome analysis was performed to elucidate biological mechanisms underlying anterior blepharitis. METHODS: All patients underwent full ophthalmological examination including Ocular Surface Disease Index score (OSDI). Measurement of non-invasive break-up time (NBUT), Oxford score, and meibography were performed. Tear film samples from treatment naïve patients with anterior blepharitis (n = 15) and age-matched controls (n = 11) were collected with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). Significantly regulated proteins were identified with a permutation-based calculation with a false discovery rate at 0.05. RESULTS: Among the 927 proteins detected, a total of 162 proteins were significantly changed. Regulated proteins were involved in cytoplasmic translation, positive regulation of B cell activation, complement activation and phagocytosis. High levels of plakin proteins, a group of proteins involved in cytoskeleton organization, were observed in anterior blepharitis, including plectin, desmoplakin, envoplakin, epiplakin, periplakin, and vimentin. The upregulation of plectin was confirmed with single reaction monitoring. Patients with anterior blepharitis had lower levels of immunoglobulin chains, VEGF coregulated chemokine 1 (CXCL17), and platelet-derived growth factor C. CONCLUSIONS: Anterior blepharitis was associated with a high level of plectin indicating a pronounced intracellular response with cytoskeletal reorganization. Our data suggest a lack of immunoglobulin chains and CXCL17 in anterior blepharitis with potential alterations in the ocular surface immune response.

Prevalence of allergic sensitization with vernal keratoconjunctivitis: A systematic review with meta-analyses.

To determine the prevalence of allergic sensitization in patients with vernal keratoconjunctivitis (VKC) and to provide an overview of published studies on this topic. We systematically searched 11 literature databases on 24 May 2021, for studies with cross-sectional data on the prevalence of positive allergy tests in patients with VKC. Our main outcome of interest was the prevalence of allergic sensitization and the allergens involved. Prevalence meta-analyses were made to provide summary estimates. We identified 33 eligible studies for qualitative review with 2122 patients with VKC. Studies were predominantly based on patients seen in ophthalmology clinics. Overall, studies reported that the most prevalent positive allergen tests were the inhaled allergens house dust mites and pollen. Twenty-nine studies were eligible for the quantitative analysis. Here, we calculated the prevalence of allergen-positive patients to 57.7% (95% confidence interval: 52.5%-62.8%). Subgroup analyses of pooled estimates on sensitization based on specific testing methods found prevalence estimates of 51.4% for conjunctival provocation test, 68.7% for total tear IgE, 58.9% for specific tear IgE, and 58.2% for skin prick test. The prevalence of allergic sensitization in patients with VKC is 57.7%, and mostly towards inhaled allergens. The most frequent positive allergens are house dust mites and pollen. Identifying possible clinically relevant allergens provide information that may aid in managing VKC, such as environmental allergy-avoidance or allergy-specific treatment.

Comparative efficacy of medical treatments for vernal keratoconjunctivitis in children and young adults: a systematic review with network meta-analyses.

PURPOSE: To systematically review the literature on the treatment of vernal keratoconjunctivitis (VKC) in children and young adults and conduct comparative efficacy analysis on clinical signs and symptoms using network meta-analyses. METHODS: We systematically searched the databases PubMed/MEDLINE, EMBASE, Cochrane Central and Web of Science on 21 October 2019 for randomized controlled trials (RCT). Studies considered had patients with VKC < 20 years of age randomized into either intervention (any medical intervention) or comparator (active treatment, placebo treatment or non-treatment control), where pre-defined outcomes (data from ≥2 weeks and as close as possible to 2 months) of symptoms (itching, tearing, photophobia and foreign body sensation) and signs (hyperaemia, punctate keratitis, Horner-Trantas dots and macropapillae) were reported. Risk of bias within studies was evaluated using the Cochrane risk of bias tool. Comparisons were made using network meta-analyses. RESULTS: We identified 39 studies with data on 2046 individuals. Twenty-three studies were eligible for quantitative analyses. None were systemic therapy. Temporal trend analysis showed that an initial focus on topical mast cell stabilizers turned to a focus on calcineurin inhibitors and a more diverse variety of pharmacological strategies. Studies varied in population, treatment duration and quality. The quantitative analysis revealed that efficacy of different therapies differed substantially across important clinical signs and symptoms, but there was a general trend of superior efficacy when using topical corticosteroids with stronger efficacy of the more potent corticosteroids. CONCLUSION: We provide an overview of RCTs comparing the efficacy of treatments for VKC in children and young adults, which we find differs across symptoms and signs. Overall, we saw a general trend of superior efficacy with topical corticosteroids. However, our findings highlight the need for better studies, consensus on core outcomes and potential for individualized therapy.

Danish teleophthalmology platform reduces optometry referrals into the national eye care system.

OBJECTIVE: The purpose of this study was to evaluate the stratification of follow-up and referral pathways after implementation of a systematic cloud-based electronic-referral teleophthalmological service for optometry-initiated ocular posterior segment disease referrals to the Danish national eye care system. METHODS AND ANALYSIS: A retrospective cohort study was conducted in the period from 1 August 2018 to 31 July 2019. Patients with suspected ocular posterior segment disease reviewed by the telemedical ophthalmology service were included. The service stratified patients into the categories: no need for follow-up, follow-up by optometrist, follow-up by the telemedical service and referral to the national Danish eye care service. RESULTS: From a pool of 386 361 customers, 9938 patients were enrolled into this study. 19.5% of all patients were referred to the Danish national eye care system, while 80.5% of the patients in the telemedical service were not, in the period from 1 August 2018 to 31 July 2019. 14.4% of the optometrist referrals did not need any follow-up, while a majority of 66.1% needed some follow-up either by the optometrist themselves or within the telemedical service. CONCLUSION: Optometrist posterior segment disease referrals can be considerably reduced with a risk stratified approach and optimal use of technology. New models can improve and streamline the healthcare system.

The eye amputated - consequences of eye amputation with emphasis on clinical aspects, phantom eye syndrome and quality of life.

In this thesis the term eye amputation (EA) covers the removing of an eye by: evisceration, enucleation and exenteration. Amputation of an eye is most frequently the end-stage in a complicated disease, or the primary treatment in trauma and neoplasm. In 2010 the literature is extensive due to knowledge about types of surgery, implants and surgical technique. However, not much is known about the time past surgery. THE PURPOSE OF THE PHD THESIS WAS: To identify the number of EA, the causative diagnosis and the indication for surgical removal of the eye, the chosen surgical technique and to evaluate a possible change in surgical technique in Denmark from 1996 until 2003 (paper I); To describe the phantom eye syndrome and its prevalence of visual hallucinations, phantom pain and phantom sensations (paper II); To characterise the quality of phantom eye pain, including its intensity and frequency among EA patients. We attempted to identify patients with increased risk of developing pain after EA and investigated if preoperative pain is a risk factor for a later development of phantom pain (paper III); In addition we wanted to investigate the health related quality of life, perceived stress, self rated health, job separation due to illness or disability and socio-economic position of the EA in comparison with the general Danish population (paper IV). THE STUDIES WERE BASED ON: Records on 431 EA patients, clinical ophthalmological examination and an interview study of 173 EA patients and a questionnaire answered by 120 EA patients. CONCLUSIONS: The most frequent indications for EA in Denmark were painful blind eye (37%) and neoplasm (34%). During the study period 1996-2003, the annual number of eye amputations was stable, but an increase in bulbar eviscerations was noticed. Orbital implants were used with an increasing tendency until 2003. The Phantom eye syndrome is frequent among EA patients. Visual hallucinations were described by 42% of the patients. The content were mainly elementary visual hallucinations, with white or colored light as a continuous sharp light or as moving dots. The most frequent triggers were darkness, closing of the eyes, fatigue and psychological stress. Fifty-four percent of the patients had visual hallucinations more than once a week. Ten patients were so visually disturbed that it interfered with their daily life. Approximately 23% of all EA experience phantom pain for several years after the surgery. Phantom pain was reported to be of three different qualities: (i) cutting, penetrating, gnawing or oppressive (n=19); (ii) radiating, zapping or shooting (n=8); (iii) superficial burning or stinging (n=5); or a mixture of these different pain qualities (n=7). The median intensity on a visual analogue scale, ranging from 0 to 100, was 36 [range: 1-89]. One-third of the patients experienced phantom pain every day. Chilliness, windy weather and psychological stress/fatigue were the most commonly reported triggers for pain. Factors associated with phantom pain were: ophthalmic pain before EA, the presence of implant and a patient reported high degree of conjunctival secretion. A common reason for EA is the presence of a painful blind eye. However, one third of these patients continue to have pain after the EA. Phantom sensations were present in 2% of the patients. The impact of an eye amputation is considerable. EA patients have poorer health related quality of life, poorer self-rated health and more perceived stress than does the general population. The largest differences in health related quality of life between the EA patients and the general population were related to role limitations due to emotional problems and mental health. Patients with the indication painful blind eye are having lower scores in all aspects of health related quality of life and perceived stress than patients with the indication neoplasm and trauma. The percentage of eye amputated which is divorced or separated was twice as high as in the general population. Furthermore, 25% retired or changed to part-time jobs due to eye disease and 39.5% stopped participating in leisure activities due to their EAs.

Review of 345 eye amputations carried out in the period 1996-2003, at Rigshospitalet, Denmark.

PURPOSE: The aim of this study was to identify the number of eye amputations, and the causative diagnoses, indications for surgery and surgical techniques applied, and to evaluate a possible change in surgical technique in a tertiary referral centre in Denmark. METHODS: The hospital database was screened using surgery codes for patients who had undergone bulbar evisceration, enucleation or orbital exenteration in the period 1996-2003. Patient records were reviewed for gender, age, time since surgery, causative diagnosis (the disease process leading to the indication for amputation), indication for eye amputation, type of surgery and whether an implant was applied. RESULTS: A total of 345 patients were identified as having undergone eye amputation during the 8-year period. Indications for eye amputation were: painful blind eye (127); neoplasm (119); infection (42); recent injury (25); disfiguring blind eye (25); prevention of sympathetic ophthalmia (5), and other reasons (2). Surgical procedures included 174 eviscerations, 154 enucleations and 17 orbital exenterations. The mean number of surgeries per year was 43.1. An orbital implant was applied in 168 patients. CONCLUSIONS: The most frequent indications for eye amputation were painful blind eye (37%) and neoplasm (34%). During the study period, the annual number of eye amputations was stable, but an increase in bulbar eviscerations was noticed. Orbital implants were used in 33% of patients in 1996 and 67% in 2003.

[Complications from eye prosthesis]. / Komplikationer ved brug af øjenproteser.

In Denmark, 3,000-4,000 people have lost an eye, they are eye amputated. The most frequent complications associated with the use of an artificial eye, eye-prosthesis, are secretion, lagophthalmos, enophthalmos, rotating prosthesis, prosthesis falling out, and exophthalmos. The wearing of an eye prosthesis and the related complications are important issues that the medical doctor should discuss with the patient.