Inhibition of STAT6 signaling by rebamipide attenuates IL-4- and IL-13-induced eotaxin expression in corneal fibroblasts.

To analyze the risk factors, clinical features, visual outcomes, and in-vivo imaging characteristics in cases of keratoconus developing keratitis following accelerated collagen cross-linking (CXL). A retrospective observational case series at a tertiary eye center in India evaluating eyes that underwent accelerated CXL from January 2021 to July 2024. Of 723 eyes undergoing CXL, 14 eyes developed infiltrative keratitis (1.93%). The majority belonged to the upper middle socioeconomic class and presented in summer and rainy seasons. The relative risk of developing infiltrates in cases ≤16 years was 2.38, and in cases with history of vernal keratoconjunctivitis, it was 0.7. The median area of epithelial defect was 12 mm 2 , and the average resolution time was 18.4 ± 12.9 days. The most common organism that was isolated was coagulase-negative Staphylococcus. The majority of the cases on anterior segment optical coherence tomography showed involvement anterior to the demarcation line. Scheimpflug imaging showed three keratometric patterns: flattening and thinning, flattening and thinning with transient steepening, and minimal to no change. Infiltrative keratitis following accelerated CXL is a rare clinical entity. Early presentation and timely management including use of topical steroids are associated with good visual outcomes.

Vernal keratoconjunctivitis (VKC) is a chronic, vision-threatening ocular allergy that primarily affects children in warm and dry climates. Diagnosis in pediatric populations is frequently delayed due to symptom overlap with other allergic conjunctivitides, lack of pediatric tools and difficulty obtaining precise histories. These delays contribute to the risk of developing shield ulcers, corneal scarring, keratoconus, and eventual blindness. Tear film analysis offers a minimally invasive solution to detect and monitor VKC by analyzing ocular surface inflammation markers. This narrative review summarizes recent literature on tear biomarkers in pediatric VKC. Some key markers include Th2 cytokines (IL-4, IL-5, IL-10), eosinophil cationic protein (ECP), matrix metalloproteinases (MMP-1, MMP-9), tear-derived micro-RNAs, and acute phase proteins like hemopexin and transferrin. These correlate with disease severity and can be used to reflect efficacy of therapy. Collection via Schirmer strips or microcapillary tubes is rapid and well-tolerated, enabling repeated monitoring. Standardization of pediatric-specific reference ranges and guidelines, and large-scale validation could potentially establish tear biomarker analysis as a gold-standard tool for VKC detection and treatment monitoring, reducing preventable vision loss in children.

Background: Vernal keratoconjunctivitis (VKC) is a chronic, recurrent allergic ocular illness that might result in corneal complications and vision loss. Various treatment options exist, but the optimal management strategy for moderate cases remains unclear. The purpose of this research is to compare the effectiveness and safety of cryotherapy, topical corticosteroid eye drops, and topical non-steroidal anti-inflammatory eye drops (NSAIDs) in the treatment of moderate VKC. Methods: This prospective randomized research involved sixty cases with moderate VKC, separated equally into 3 groups: Group A (cryotherapy), Group B (fluorometholone 0.1% suspension), and Group C (nepafenac 0.1% eye drops). Cases have been followed for six months, and outcomes assessed included resolution of symptoms and signs, recurrence, and complications. Results: At three months, no significant intergroup differences were observed in symptoms, conjunctival hyperemia, papillae, or keratitis (p > 0.05), except for Trantas dots distribution (p = 0.0375). At six months, all groups demonstrated significant improvement. Group C showed the highest resolution of palpebral papillae (70%) and the lowest relapse rate (35%), compared with Group A (80% relapse) and Group B (50% relapse). No serious treatmentrelated complications occurred in any group. Conclusion: Cryotherapy, corticosteroids, and NSAIDs are all effective in managing moderate VKC. However, cryotherapy remains a safe and useful non-pharmacological option, particularly for refractory cases.

Effectiveness of Corticosteroid-Sparing Topical Treatments for Vernal Keratoconjunctivitis in Children: A Report by the American Academy of Ophthalmology.

Vernal keratoconjunctivitis (VKC) represents far more than a typical allergic eye disease. It is a distinct and often underestimated chronic inflammatory condition that primarily affects children during critical stages of physical and emotional development. Though frequently grouped with seasonal allergic conjunctivitis, VKC differs significantly in its immunopathology, clinical presentation, and long-term implications. Its intense ocular symptoms and its potential for corneal damage and substantial psychosocial burden require, rather than symptom control, coordinated and multidisciplinary management. This narrative review explores VKC from every angle, with a particular focus on its implications for pediatric care. VKC, in fact, represents a genuine clinical challenge: as its symptoms can mimic milder forms of conjunctivitis, its course is often unpredictable, and its treatment requires balancing efficacy and safety in vulnerable age groups. We examined the immunological mechanisms that make it a model of localized Th2 inflammation, the diagnostic pitfalls that delay recognition, and the evolving treatment landscape, from conventional therapies like cyclosporine A and tacrolimus to innovative agents such as omalizumab and dupilumab. We also highlighted the role of emerging biomarkers, the influence of environmental and microbiome factors, and the urgent need for standardized care pathways. As research continues to expand our understanding, VKC is emerging as a prime example of how personalized medicine and translational science can intersect to address complex immune-mediated diseases in children. For the ones treating pediatric allergic disorders, VKC is no longer a rare curiosity: it is a clinical challenge worth understanding deeply.

Regeneration potential and remodelling of juvenile cornea resulting from vernal keratoconjunctivitis

ObjectivesVernal keratoconjunctivitis (VKC) is a recurrent allergic inflammation of the conjunctiva characterized by itchiness. The cytokine IL-31 is involved in itch and inflammation in other conditions, so we investigated whether it plays similar role in VKC.MethodsWe estimated messenger RNA (mRNA) IL-31 expression in giant papillae (GP) with real-time polymerase chain reaction (RT-PCR). We used immunohistochemistry to examine IL-31 receptor (IL-31R) expression in neurons and epithelial cells in GP. We then performed fluorescence-activated cell sorting and immunofluorescence to examine IL-31R expression in cultured human conjunctival epithelial cells (HConEpiCs) either treated or not treated with various cytokines. Next, we examined the expression of phosphorylated signal transducer and activator of transcription 3 (P-STAT3) and suppressor of cytokine signaling 3 (SOCS3) in the epithelium of GP and control specimens using immunohistochemistry. Last, we used DNA microarray analysis and RT-PCR to investigate whether recombinant IL-31 induced expression of various genes in HConEpiCs.ResultsIL-31 expression was elevated in GP compared with control specimens. Although many neuron fibers innervated GP, none was found to express IL-31R. IL-31R was expressed in the epithelium of GP and in HConEpiCs, and its expression in HConEpiCs was not altered by any of the investigated cytokines. Recombinant IL-31 increased SOCS3 mRNA expression. Strong P-STAT3 expression was observed in the epithelium of GP, but SOCS3 expression was not observed.ConclusionsIncreased IL-31 in GP of VKC patients may not directly influence itch sensation via neuron fibers and inflammation via the expression of P-STAT3 and SOCS3.

To assess the one-year visual, refractive, and tomographic outcomes of corneal collagen cross-linking (CXL) performed at diagnosis in Indian children with keratoconus and to evaluate its safety in eyes with controlled vernal keratoconjunctivitis (VKC). Thirty-eight eyes of 30 children (9-18 years) diagnosed with keratoconus underwent standard epithelium-off CXL (Dresden protocol). "At diagnosis" was defined as treatment within four weeks of first topographic confirmation. Outcome measures included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), keratometric indices (flat K, steep K, apical K), pachymetry, and endothelial cell density. Statistical analysis included paired and adjusted comparisons with 95% confidence intervals (CIs). UCVA improved from 0.72 ± 0.46 to 0.45 ± 0.42 logMAR (P < 0.001) and BCVA from 0.37 ± 0.30 to 0.21 ± 0.28 logMAR (P < 0.001). MRSE improved by 1.72 D (P < 0.001). Steep K and apical K flattened by 2.02 D and 2.26 D respectively (P < 0.001). Endothelial cell counts were stable. Subgroup analysis showed no difference between VKC and non-VKC eyes. Three patients developed transient sterile infiltrates that resolved with medical therapy. Performing CXL at diagnosis is safe and effective in halting pediatric keratoconus progression while improving visual and refractive outcomes. Early treatment is particularly relevant for high-risk ethnic groups such as Indian children, where keratoconus is aggressive and rapidly progressive.

Comprehensive assessment of tear film dynamics in pediatric vernal keratoconjunctivitis using a novel non-invasive device (MYAH).

Prevalence of vernal keratoconjunctivitis in Canada: a cross-sectional survey study.

The hallmark of acute corneal hydrops (CH) is Descemet membrane (DM) rupture that leads to the influx of fluid into the cornea causing corneal edema. Multiple risk factors have been related to an increased incidence of CH in keratoconus (KC) patients, such as Down's syndrome, atopy, vernal keratoconjunctivitis, eye rubbing, and an earlier age of KC onset. Penetrating keratoplasty (PKP), deep anterior lamellar keratoplasty (DALK), compression sutures, cyanoacrylate tissue adhesive with bandage contact lens (BCL), intracameral gas injection, and amniotic membrane transplant (AMT) are some of the conservative and surgical methods used to treat CH. Compared to KC without a history of CH, the need for PKP in patients with healed hydrops is higher due to preexisting DM rupture. Thus, the majority of surgeons conduct PKPafter CH. On the other hand, some corneal surgeons choose to perform DALK over PKPas it spares the host endothelium. In this narrative review, we compare DALK to PKP for corneal hydrops in KC, evaluating the challenges, advantages, and visual and refractive outcomes.

ABSTRACT Purpose This study aims to analyze the expression of presumably critical inflammatory mediators including cytokines, chemokines, secretory, binding, and matrix proteins, and IgE in Vernal keratoconjunctivitis (VKC)-relevant age groups: children, adolescents, and adults. Methods The tears (n = 16) and serum (n = 12) samples from active, chronic VKC cases, without treatment at the time of sampling, were collected from the tertiary eye care centers of L V Prasad Eye Institute, located in Hyderabad and Bhubaneswar, during 2021–2022. The age-matched healthy individuals were taken as controls. The subjects were grouped as: children (1–11 years), adolescents (12–21 years), and adults (> 21 years). The expression of a specific panel of Th1- (IL-36γ and MMP-9) and Th2-inflammatory mediators (IL-6, Vitamin D-binding protein (VDBP), MUC5AC, FcεR1, MCP-1, IgE, GM-CSF) was analyzed through ELISA. Results Compared to controls, the expression of IgE was upregulated in tears and serum samples of all VKC patients, whereas IL-6, MMP-9, and MUC5AC were upregulated, and VDBP was downregulated in children’s tear samples. The VDBP and MCP-1 recorded the highest and lowest protein expression (pg/ml) among all the inflammatory mediators, respectively. The IL-36γ was upregulated in tears and serum samples of adolescents and adults. Conclusions Our results suggest differential expressions of chosen Th1- and Th2-mediators in tears and serum samples of children, adolescents, and adults with active VKC. Compared with controls, our findings specifically suggest: i) upregulation of IgE, IL-6, MMP-9, and MUC5AC, and downregulation of VDBP in tear samples of children, and ii) upregulation of IgE and IL-36γ in adolescents and adults.

Vernal keratoconjunctivitis (VKC) is a chronic bilateral ocular allergic disease affecting mainly children and adolescents. Perilimbal pigmentation (PLP) has been noted as a new sign of VKC in pigmented race of Asian and African origin. To analyze the etiology, clinical significance, and pathophysiology of PLP, and to explore the possible association between ultraviolet (UV) exposure and the presence of PLP in VKC. A PubMed search of articles between January 1983 and January 2024 on VKC with PLP was performed. PLP takes the appearance of spotty pigmentation in the interpalpebral conjunctiva. Activation and proliferation of the melanocytes in the limbus in the status of inflammation had been proposed as possible pathogenesis of PLP. However, the clinical significance of PLP in the process of VKC were still controversial. VKC with PLP were mostly seen in pigmented races in equatorial region with hot, dry climates and strong UV. The regionality of VKC patients with PLP and the interpalpebral distribution of pigmentation suggest possible association of PLP with UV. Elucidating this issue will help to prevent and treat this regional and racial specific VKC.

Purpose: To study the clinical and epidemiological characteristics of steroid-induced glaucoma (SIG) occurring during vernal keratoconjunctivitis (VKC). Methods: Retrospective descriptive study including 20 patients followed for VKC complicated by ocular hypertension secondary to topical corticosteroid use. Results: The mean age was 13.5 years (range 8–20) with a marked male predominance (85%). Steroid-induced hypertension occurred after an average of 6.5 months of instillation. The corticosteroids involved were dexamethasone (70%) and fluorometholone (30%). Visual acuity was reduced in 35% of cases. Glaucoma was confirmed in 8 cases (40%), while 12 (60%) presented with reversible ocular hypertension. All patients received topical hypotensive treatment, and 3 required trabeculectomy. The evolution was favorable in 90% of cases after corticosteroid withdrawal and replacement by non-steroidal therapy. Conclusion: Steroid-induced glaucoma is a serious but preventable complication of VKC. Patient education and regular intraocular pressure monitoring are essential to prevent irreversible visual loss.

Kaphaja Netra Abhishyanda, as described in Ayurvedic literature, is an ocular disorder affecting all structures of the eye. It commonly presents with heaviness of eyelids (Guruta), itching (Kandu), excessive and frequent tearing (MuhurmuhurSrava), along with burning sensation and photophobia. When the clinical features of this condition are compared with modern ophthalmological descriptions, it shows a close resemblance to vernal keratoconjunctivitis (VKC), a type of allergic conjunctivitis frequently seen in children and young individuals. VKC has emerged as a significant reason for corneal complications and potential vision loss.This allergic inflammation of the conjunctiva is usually triggered byenvironmental allergens such as pollen, dust, smoke, animal dander, and mites, leading to symptoms like intense itching, conjunctival congestion, and papillary hypertrophy. The term “Spring Catarrh” is also used for VKC, indicating its seasonal tendency during Vasanta Ritu, which is known as the Kapha aggravation phase according to Ayurveda. This seasonal pattern, along with the susceptibility of the childhood age group, correlates well with the Ayurvedic concept of KaphaPrakopa during early life.

To characterize nationwide real-world practice patterns and complications of pediatric ocular surface inflammatory diseases (POSID) using a large US health insurance claims database. This retrospective cohort study analyzed patients younger than 18 years diagnosed with POSID in the Optum Labs Data Warehouse between 2018 and 2019. Blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), and vernal keratoconjunctivitis (VKC) were identified by ICD codes. Clinical data from 6 months before to 3 years after the index visit were assessed. Multivariate logistic regression identified risk factors for amblyopia. Among 6116 children (67.1% aged 5-15 years; 56.6% male), HSK showed the highest baseline rates of corneal scarring (7.5%) and ulceration (5.5%), compared with BKC (2.3%, 2.7%) and VKC (1.1%, 0.9%) (P < 0.001). High-potency topical corticosteroids were more frequently prescribed for BKC (17.8%) than HSK (15.0%) or VKC (14.2%) (P = 0.02), while topical immunomodulators were used in only 1.7% of cases despite recommendations. Amblyopia prevalence rose from 2.5% to 4.5% over 3 years, with stromal scarring at diagnosis (odds ratio 2.43, 95% confidence interval 1.40-4.24) and high-potency corticosteroid use (odds ratio 1.60, 95% confidence interval 1.17-2.18) as independent risk factors. POSID subtypes exhibit distinct clinical features, significant differences in management, and progressive complications over time. Nationwide patterns show over-reliance on corticosteroids, underuse of immunomodulators, and gaps between guideline recommendations and practice, underscoring the need for earlier recognition, steroid-sparing therapy, and sustained inflammation control.

To investigates the gut microbiota in patients with vernal keratoconjunctivitis (VKC) compared with normal subjects. A case-control study was conducted involving 32 patients with VKC and 16 age- and sex-matched healthy controls. Fecal samples were collected and analyzed using quantitative PCR to measure the abundance of 5 bacterial groups: Prevotella, Firmicutes, Faecalibacterium, Bifidobacterium, and Bacteroides. In addition, clinical severity scores for VKC symptoms and signs were recorded and analyzed. Patients with VKC exhibited significant microbial dysbiosis compared with controls, including an upregulation of Prevotella (mean fold change 21.579; P <0.001) and downregulation of Firmicutes, Faecalibacterium, and Bifidobacterium (P < 0.01 for all). No significant correlations were observed between microbial levels and clinical severity scores. The study identifies significant gut microbial imbalances in patients with VKC, suggesting that dysbiosis may play a role in the disease. Microbiota-targeted interventions, such as probiotics and dietary modifications, may offer novel strategies for managing VKC.

Background: Keratoconus (KC), a progressive, corneal, ectatic disease varies in prevalence globally. Differences and similarities in KC prevalence have been observed, and despite clinicians anecdotally reporting many KC cases, no empirical evidence of KC prevalence in Tanzania exists. Aim: This study aimed to determine the KC prevalence and demographic and clinical profiles of patients attending a tertiary hospital. Setting: The study was conducted at the Kilimanjaro Christian Medical Centre in Tanzania. Methods: The study applied a quantitative, retrospective study design whereby identified data were extracted from clinical records of patients aged 12 years – 45 years, presenting with corneal abnormalities, between the years 2016 and 2020. Statistical Package for Social Sciences was used for data analysis. Results: Of the 140 523 presenting patients, 1089 (0.77%) had corneal abnormalities, among whom KC prevalence was 10.0%. Patients were more likely to be men (odds ratio [OR]:1.5; P = 0.033) referred from lower-level clinics (OR:2.4; P ≤ 0.001) and residing in the Arusha region (OR:1.8; P = 0.012). Clinically, KC patients were more likely than non-KC to have vernal keratoconjunctivitis (VKC) (OR:3.8; P ≤ 0.001) and ocular allergies (OR:1.6; P = 0.028); be astigmatic (OR:6.5; P = 0.001) and myopic (OR:2.5; P = 0.001). Conclusion: The prevalence of KC among patients with corneal abnormalities is high, with significant predominance in patients with myopia, astigmatism and VKC. Data quality revealed a need for KC clinical guidelines, improved record keeping. Contribution: First study providing empirical KC data to guide improved patient care planning in Kilimanjaro.

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, and severe allergic inflammatory disorder of the ocular surface that predominantly affects children and adolescents in warm, dry climates. Its pathogenesis involves complex immune responses, primarily mediated by IgE, mast cells, eosinophils, and Th2 cytokines. VKC can lead to significant ocular discomfort and, in severe cases, visual impairment due to corneal complications. This review aims to provide a comprehensive update on the pharmacotherapeutic advancements in VKC, ranging from conventional treatments like mast cell stabilizers and corticosteroids to emerging options such as immunomodulators and biologic agents. A structured review of the literature was conducted, analyzing current and evolving therapeutic approaches based on their mechanisms of action, clinical efficacy, safety profiles, and limitations. While conventional therapy remains effective for mild to moderate cases, the advent of immunomodulators (cyclosporine, tacrolimus) and biologics (e.g., omalizumab) offers hope for managing refractory and severe forms of VKC with better disease control and fewer side effects. Additionally, advancements in ocular drug delivery systems enhance the therapeutic potential of existing drugs. The therapeutic landscape of VKC is evolving rapidly, with immunologically targeted therapies emerging as promising alternatives. Individualized treatment strategies based on disease severity and immune profile may become the future standard of care.