Vernal keratoconjunctivitis in Down syndrome: a case report.

BACKGROUND: Down syndrome (DS) or Trisomy 21 is the most common chromosomal disease and is characterized by possible heart defects, cognitive impairment and visual disorders. CASE PRESENTATION: We describe for the first time a 17-year-old Caucasian girl suffering from Down syndrome associated with vernal keratoconjunctivitis (VKC), a rare disorder of the anterior segment of the eye, characterized by intense photophobia, redness, watering eyes and itching due to an inflammatory-allergic reaction of the cornea and conjunctiva. On slit-lamp examination, the girl showed conjunctival hyperemia, papillary hypertrophy, giant papillae and corneal leukoma in right eye as a result of a previous corneal ulcer. A successful topical immunosuppressant therapy with cyclosporin 1% was started. CONCLUSION: So far, to our knowledge, this is the first description of VKC in a patient with DS. Finding an inflammatory-allergic disease such as VKC in DS is unusual but it must be taken into account because keratoconus, one of the most frequent eye pathologies in DS, can be secondary to an unrecognized VKC.

Diagnosis and management of keratoconus by eye care practitioners in Kenya.

BACKGROUND: To explore current eye care practice in keratoconus diagnosis and management in Kenya. METHODS: An online questionnaire was distributed to ophthalmic clinical officers (OCO) and optometrists. RESULTS: A total of 203 responses were received from 52 OCOs and 151 optometrists with a response rate of 24.4% and 53.5% respectively. The majority reported having access to retinoscopes (88.5%; p = 0.48) and slit lamps (76.7; p = 0.14). Few practitioners had access to a corneal topographer (13.5%; p = 0.08) and rigid contact lens (CL) fitting sets (OCOs 5.8%, optometrists 33.8%; p < 0.01). One-third did not feel that retinoscopy (38.7%; p = 0.21), slit lamp findings (30.3%; p = 0.10) and corneal topography (36.6%; p = 0.39) are important investigations in keratoconus diagnosis. Corneal topography was not recommended in two-thirds of patients (59.0%; p = 0.33) with vernal keratoconjunctivitis (VKC). The majority counselled against eye rubbing in mild (73.6%; p = 0.90) VKC, 52.9% in moderate (p = 0.40) and 43.6% in severe (p = 0.24) cases. The majority prescribed spectacles in mild (90.2%; p = 0.95), 29% (p = 0.97) in moderate and 1.9% (p = 0.05) in severe cases. When the binocular best corrected visual acuity (BCVA) with spectacles was ≤ 6/18, 76.9% of OCOs and 58.9% of optometrists referred for CLs (p = 0.02). When binocular BCVA with CLs dropped to ≤ 6/18, 83.7% (p = 0.18) referred to the ophthalmologist for surgical intervention. Few OCOs fitted rigid CLs (15.4% OCOs, 51.0% optometrists; p = 0.01), majority referred to optometrists (82.7% OCOs, 43.7% optometrists; p < 0.01). Progression was monitored in 70.1% (p = 0.11) of mild, 50.9% (p = 0.54) moderate and 25.3% (p = 0.31) advanced cases. Few OCOs (15.4%) performed corneal cross-linking (CXL). A few respondents (5.4%; p = 0.13) did not know when to refer keratoconus patients for CXL. Co-management with ophthalmologists was reported by 58.0% (p = 0.06) of respondents. CONCLUSION: The results of this study highlight the need to map services for keratoconus patients, review current curricula and continuous education priorities for mid-level ophthalmic workers, develop guidelines for the diagnosis and management of keratoconus and improve interdisciplinary collaboration.

Lirentelimab for severe and chronic forms of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

Impact of Exposomes on Ocular Surface Diseases.

Ocular surface diseases (OSDs) are significant causes of ocular morbidity, and are often associated with chronic inflammation, redness, irritation, discomfort, and pain. In severe OSDs, loss of vision can result from ocular surface failure, characterised by limbal stem cell deficiencies, corneal vascularisation, corneal opacification, and surface keratinisation. External and internal exposomes are measures of environmental factors that individuals are exposed to, and have been increasingly studied for their impact on ocular surface diseases. External exposomes consist of external environmental factors such as dust, pollution, and stress; internal exposomes consist of the surface microbiome, gut microflora, and oxidative stress. Concerning internal exposomes, alterations in the commensal ocular surface microbiome of patients with OSDs are increasingly reported due to advancements in metagenomics using next-generation sequencing. Changes in the microbiome may be a consequence of the underlying disease processes or may have a role in the pathogenesis of OSDs. Understanding the changes in the ocular surface microbiome and the impact of various other exposomes may also help to establish the causative factors underlying ocular surface inflammation and scarring, the hallmarks of OSDs. This review provides a summary of the current evidence on exposomes in various OSDs.

Biologics for allergy: therapeutic potential for ocular allergic diseases and adverse effects on the eye.

Biologics applying antibodies against IgE, IL-5, IL-5 receptor α, IL-4 receptor α, and IL-13 have dramatically improved recent treatment outcomes in allergic diseases including asthma, rhinitis, and atopic dermatitis. However, these drugs have not been approved for ocular allergic diseases such as allergic conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis. Although the putative mechanisms suggest that these drugs should have beneficial effects in patients with ocular allergies and some studies have reported such beneficial effects, various adverse ocular symptoms have also been observed in clinical trials and off-label use studies. Since ocular allergic diseases have distinct pathogeneses, each biologic drug must be examined regarding specific effects on each ocular allergy. For example, IgE-mediated type 1 hypersensitivity plays a critical role in allergic conjunctivitis. By contrast, T cells and eosinophilic and non-IgE-mediated type 2 inflammation play important roles in vernal keratoconjunctivitis. Allergists must fully understand the effects of each drug on the eye. This review outlines both potential therapeutic and adverse effects of various biologics on allergic diseases of the eye.

Corneal biomechanical properties in vernal keratoconjunctivitis and its subtypes: a preliminary study.

PURPOSE: To explore the corneal biomechanical properties (CBPs) of patients with vernal keratoconjunctivitis (VKC) and the discrepancies among three subtypes of VKC including palpebral, limbal, and mixed forms. METHODS: Forty eyes of 20 VKC patients and twenty eyes of ten non-VKC patients were included in this case-control study. Patients with VKC were further divided into three subtypes (six patients in Palpebral form, five patients in limbal form, and nine patients in mixed form). The CBPs of all patients were obtained from the Corneal Visualization Scheimpflug Technology (Corvis ST). RESULTS: First applanation (A1) length, Ambrosio relational thickness in horizontal (ARTh), and stiffness parameter at first applanation (SP-A1) were significantly lower in the VKC group while A1 velocity was significantly higher in the VKC group (p < 0.05), compared to the non-VKC group. Furthermore, A1 velocity presented a positive correlation with disease course (p < 0.05). In addition, VKC patients of limbal form had lower central corneal thickness (CCT), SP-A1, and higher deformation amplitude ratio (DA ratio), compared to the other two subtypes (p < 0.05). Besides, patients in limbal form had higher A1 velocity, integrated radius, and corneal biomechanical index (CBI) compared with mixed form, and lower A1 length than palpebral form (p < 0.05). CONCLUSIONS: The corneas of VKC patients were softer and more protruded compared with the control group, and the property of steepness was closely related to disease course. VKC patients in limbal form were more inclined to be keratoconus than the other two subtypes due to their CBPs` discrepancies.

Evaluation of corneal epithelial thickness mapping using anterior segment OCT in children with vernal keratoconjunctivitis.

PURPOSE: To evaluate the corneal epithelial thickness by anterior segment OCT in children with vernal keratoconjunctivitis (VKC) compared to normal participants. PATIENT AND METHODS: A cross-sectional case control observational study was conducted on children aged from 5 to 18 years with VKC. The study included 142 eyes divided into two groups: 71 eyes of VKC group and 71 eyes of age matched control group. Anterior segment OCT epithelial mapping for the central 5-mm was done to evaluate epithelial thickness-based variables. RESULTS: Corneal epithelial thickness mapping showed significant superior thinning (51.07 ± 4.11) µm in VKC group compared to controls (52.54 ± 2.01) µm (p = 0.008), a decreased MIN epithelial thickness (45.99 ± 6.52) µm compared to controls (50.11 ± 1.91) µm (p < 0.001) and more negative (MIN-MAX) value (- 11.77 ± 9.38) indicating focal epithelial thinning compared to (- 5.80 ± 1.88) in controls (p = 0.001). In palpebral VKC, MIN epithelial thickness showed significant thinning (48. 38 ± 3.45) µm compared to controls (50.11 ± 1.91) µm (p = 0.001). Eyes with mixed VKC showed superior epithelial thinning (50.70 ± 4.59) µm compared to (52.54 ± 2.01) µm in controls (p = 0.025) and significant decreased MIN epithelial thickness (43.78 ± 7.83) µm compared to (50.11 ± 1.91) µm in control group. CONCLUSIONS: VKC is a disease primarily affecting the corneal epithelium. Corneal epithelial thickness mapping may be considered to assess the integrity of the ocular surface in eyes with VKC, and to detect corneal epithelial changes. Disease phenotype may influence the corneal epithelial changes, and the disease duration is another factor influencing these changes.

Epithelial barrier dysfunction in ocular allergy.

The epithelial barrier is the first line of defense that forms a protective barrier against pathogens, pollutants, and allergens. Epithelial barrier dysfunction has been recently implicated in the development of allergic diseases such as asthma, atopic dermatitis, food allergy, and rhinitis. However, there is limited knowledge on epithelial barrier dysfunction in ocular allergy (OA). Since the ocular surface is directly exposed to the environment, it is important to understand the role of ocular epithelia and their dysfunction in OA. Impaired epithelial barrier enhances allergen uptake, which lead to activation of immune responses and development of chronic inflammation as seen in allergies. Abnormal expression of tight junction proteins that helps to maintain epithelial integrity has been reported in OA but sufficient data not available in chronic atopic (AKC) and vernal keratoconjunctivitis (VKC), the pathophysiology of which is not just complex, but also the current treatments are not completely effective. This review provides an overview of studies, which indicates the role of barrier dysfunction in OA, and highlights how ocular barrier dysfunction possibly contributes to the disease pathogenesis. The review also explores the potential of ocular epithelial barrier repair strategies as preventive and therapeutic approach.

Sulforaphane inhibits cytokine-stimulated chemokine and adhesion molecule expressions in human corneal fibroblasts: Involvement of the MAPK, STAT, and NF-κB signaling pathways.

Chemokines and adhesion molecules are major inflammatory mediators of chronic and recurrent vernal keratoconjunctivitis (VKC). Sulforaphane (SFN) is a natural plant extract that is known to have anti-inflammatory and antioxidant properties. SFN is demonstrated to be effective against a variety of human diseases. The current investigation examines the effects and the molecular mechanisms of SFN on cytokine-induced human corneal fibroblasts (HCFs) expression of adhesion molecules and chemokines. HCFs were exposed to both interleukin (IL)-4 and tumor necrosis factor (TNF)-α in the absence or presence of SFN treatment. The levels of thymus- and activation-regulated chemokine (TARC) and eotaxin-1 in culture supernatants were evaluated using enzyme-linked immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction analysis (RT-PCR) enabled quantification of mRNA levels of vascular cell adhesion molecule (VCAM)-1, eotaxin-1, and TARC along with cytokine receptors. An immunoblotting assay was used to evaluate the activities of VCAM-1, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), signal transducer and activator of transcription factor (STAT)6 pathways, along with the expression of the cytokine receptors including IL-4 receptor (R)α, IL-13Rα1, TNFRI, as well as TNFRII. SFN inhibited TARC and eotaxin-1 release in HCFs stimulated by TNF-α and IL-4 in a manner dependent on dose and time. SFN suppressed transcriptions of TARC, eotaxin-1, and VCAM-1. Furthermore, the mRNA and protein expression levels of IL-4Rα, TNFRI, and TNFRII were also attenuated by SFN exposure, however, those of IL-13Rα1 remained unaffected. In addition, SFN downregulated the expression of VCAM-1 and the phosphorylation of MAPKs, IκBα, and STAT6. These results suggest that SFN inhibited cytokine-stimulated TARC, eotaxin-1 secretion as well as VCAM-1 expression in HCFs, with these effects likely occurring as a result of cytokine receptor inhibition and attenuation of MAPK, NF-κB, and STAT6 signaling. SFN may therefore have therapeutic potential in VKC treatment.

Treating refractory corneal hydrops in a male patient with vernal keratoconjunctivitis and mental retardation: a case report.

BACKGROUND: Keratoconus is the most common noninflammatory bilateral corneal ectasia. Vernal keratoconjunctivitis (VKC) and eye rubbing may be associated with keratoconus in children and young adults. Timely management of advanced keratoconus is important to improve visual quality. In addition, it is challenging to carry out VKC treatment with an intent to avoid the occurrence of punctate epithelial keratitis, ulceration, or corneal neovascularization on corneal grafts. CASE PRESENTATION: We report the case of an 18-year-old male patient with a long-term history of mental retardation due to megalencephaly presenting with acute onset of corneal hydrops with prominent bulging and refractory steroid-induced glaucoma of the right eye. The topography of the right eye was unavailable due to advanced ectasia, and that of the left eye revealed central steepening with inferior-superior dioptric asymmetry. According to the clinical findings, the patient was diagnosed with keratoconus. Because of progressive corneal opacity and neovascularization, the patient underwent penetrating keratoplasty (PK) with combination of interrupted and intrastromal running suturing after receiving a preoperative subconjunctival injection of bevacizumab in his right eye, followed by lower eyelid correction. After surgery, the patient was treated with 0.1% tacrolimus dermatological ointment, 0.1% cyclosporine eye drops, artificial tears, and 0.5% loteprednol for keratoplasty and VKC. Repeated education on avoiding eye rubbing was offered to the patient. Two years after PK treatment, his best-corrected visual acuity of the right eye successfully improved from hand motion at 10 cm preoperatively to 6/20 postoperatively. CONCLUSIONS: Large-diameter PK with intrastromal suturing technique for advanced keratoconus could achieve better visual outcomes and avoid suture-related complications. In addition, tacrolimus dermatological ointment rather than tacrolimus topical eye drops or ointment showed satisfactory efficacy when combined with topical cyclosporine and steroid that no significant VKC reactivation were noted after PK.

Executive summary: Japanese guidelines for allergic conjunctival diseases 2021.

Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.

When to start tacrolimus ointment for vernal keratoconjunctivitis? A proposed treatment protocol.

PURPOSE: The aim of this study was to compare treatment regimens of tacrolimus and of topical steroids for VKC and suggest a treatment protocol according to our clinical experience. METHODS: This retrospective, nonrandomized case series enrolled 85 patients with VKC. Patients were classified clinically according to severity (mild, moderate, severe) and were treated according to a suggested protocol. Analysis was made according to treatment received: tacrolimus ointment as first line treatment (tacrolimus 1st line), tacrolimus ointment after topical steroid drops treatment (tacrolimus 2nd line) and topical steroid drops or artificial tears alone (topical steroid and tears group). RESULTS: Significant improvements in clinical signs and symptoms were achieved under tacrolimus treatment 14 months in the moderate group and 5 months in the severe group. The longest duration of treatment was for tacrolimus 2nd line group (p = 0.031) and the mean number of visits in the clinic was the highest. The mean number of topical treatments per day was higher in the topical steroid and tears group (2.6 times) than in the two tacrolimus groups (1.3 times for both). The mean time needed to achieve disease remission or relief did not differ between the tacrolimus 1st line and 2nd line groups. CONCLUSION: Tacrolimus treatment is effective and safe for VKC. Tacrolimus as 1st line treatment may be preferred for severe cases, for faster disease remission compared to tacrolimus as 2nd line treatment; and with fewer topical treatments per day compared to topical steroids.

Health-related quality of life in children at the diagnosis of Vernal Keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, allergic condition mostly affecting children. Clinical evaluations may not necessarily reflect the impact of the disease on the patients' health-related quality of life (HRQoL). We aimed to evaluate HRQoL in children at VKC diagnosis and to analyze correlations between HRQoL and clinical and laboratory variables. METHODS: We studied 5- to 12-year-old patients with VKC. Data on clinical history, instrumental eye evaluations, blood examinations, and visual analog scale (VAS) for the subjective symptoms were collected. HRQoL was assessed through a disease-specific validated Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire. RESULTS: Seventy subjects were included in the analysis (female/male: 10/60; tarsal/mixed VKC form: 36/34). Clinical severity of VKC according to the Bonini scale was as follows: 14, mild; 36, moderate; and 20, severe. No significant difference was found concerning the distribution of patient age, gender, and history of allergic manifestations between tarsal and mixed VKC. A significant positive correlation was found between all QUICK scores and VAS scores, including different VAS subscale, while no significant correlation was found between QUICK scores and total sign scores, Schirmer's test, and corneal thickness. The presence of active severe VKC was not associated with worse HRQoL. CONCLUSIONS: Our evidence shows that VKC patients experience impairment of HRQoL, especially in relation to the perception of symptoms independently of the ophthalmologic changes found, and that the QUICK questionnaire could be a useful tool to evaluate HRQoL in children with VKC, which may improve patients' classification and management.

Comparative profile of ocular surface microbiome in vernal keratoconjunctivitis patients and healthy subjects.

PURPOSE: To compare ocular surface microbiome and its antibiotic sensitivity in vernal keratoconjunctivitis (VKC) with normal ocular surface. METHODS: In this case-control study, thirty patients each with clinical diagnosis of VKC and age-matched controls with normal ocular surface were enrolled. Tear film samples were collected from each group and subjected to microbial evaluation with microscopy, conventional culture methods, and polymerase chain reaction (PCR). Microbial diversity and antibiotic sensitivity patterns were analyzed. RESULTS: Most patients (67%) belonged to severe grades (3 and 4) of VKC, and allergic history could be elicited in 20%. On culture, bacteria were isolated in 50% of VKC patients and 47% of control group. Staphylococcus species were identified in 70% VKC group and 57% control group. S. aureus growth was seen in 52% and 21% of VKC patients and controls, respectively. S. pneumoniae was isolated only in controls (29%) (p<0.05). Confluent colonies (≥10 colonies/µl) were seen in 70% of VKC patients and 14% of controls (p<0.05). Fluoroquinolone resistance was more among higher grades of VKC (50%) (p<0.01) and was observed in 46% of VKC patients and 23% of control group (p<0.01). Both groups were negative for HSV-1 DNA and fungal growth. CONCLUSION: Staphylococcus, the most common ocular surface flora, was predominant in VKC patients. Microbial analysis revealed similar microbial diversity in both groups. However, bacterial load was higher in VKC. Increased fluoroquinolone resistance was observed in VKC patients with more resistance among higher grades. Fungi and HSV-1 were not seen in VKC or normal ocular surface.

Long Term Outcomes of Surgical Excision of Giant Papillae with Mitomycin C and Amniotic Membrane Transplantation in the Treatment of Refractory Palpebral Vernal Keratoconjunctivitis.

Background and Objectives: To report the long-term outcomes of patients with refractory Vernal Keratoconjunctivitis (VKC) who underwent surgical excision of giant papillae (GP) with mitomycin C (MMC) 0.02% and amniotic membrane transplantation (AMT). Materials and Methods: This is a retrospective interventional single-center case series including five eyes of four patients who had refractory, symptomatic VKC with GP, along with corneal shield ulcers and/or punctate epithelial erosions. They underwent surgical excision of GP with MMC 0.02% alone (1 eye) or with MMC 0.02% and AMT (4 eyes). Their long-term visual and surgical outcomes were studied. Results: All subjects were male with bilateral involvement and mean age of presentation 9.8 years. The surgery was uneventful in all cases. Amongst the four eyes which underwent MMC with AMT, only one eye demonstrated papillary regrowth requiring repeat surgery. Postoperative follow-up ranged from 59 to 77 months (median 66 months). Four patients had the best corrected visual acuity (BCVA) >/= 6/9.5. One patient had BCVA 6/15 at the final follow-up due to the presence of anterior corneal stromal scar and poor ocular surface. Conclusions: Surgical excision of GP in combination with MMC and AMT, in refractory VKC, is a good treatment option with better clinical outcomes over a longer follow-up.

Corneal and lens densitometry in patients with vernal keratoconjunctivitis.

AIM: To evaluate corneal and crystalline lens densitometry in patients with vernal keratoconjunctivitis (VKC). METHODS: This is a case-control study. Patients with VKC and age-gender-matched healthy controls underwent a complete ophthalmologic examination with corneal and crystalline lens densitometry measurements. Additionally, the anterior chamber parameters comprise anterior and posterior Kmean and astigmatism, anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), pachymeter, and corneal volume (CV). Patients who had clinically grade 0 or grade 1 VKC and with only tarsal conjunctiva involvement during the conductance of the study were included. The variables were compared statistically. RESULTS: One hundred and nine eyes were included in the study, in which fifty-one were in the VKC group. There were 25 males in the VKC group (26 female) and 22 males in the control group (36 female). A statistically significant difference was found between the groups in terms of posterior corneal astigmatism (p = 0.02). The mean corneal pachymeter, CV, ACD, ACA, and ACV were similar in both groups (p = 0.63, p = 0.26, p = 0.60, p = 0.41, and p = 0.32, respectively). The total mean corneal densitometry in the zones extending from 6 to 10 mm and 10 to 12 mm was increased in the VKC group compared to the control group (p = 0.04 and p = 0.012, respectively). The mean crystalline lens was found to be denser in the VKC group compared to the control group (8.96 ± 1.6 vs. 8.5 ± 0.57, respectively, p = 0.04). CONCLUSION: Posterior corneal astigmatism is increased in VKC cases in comparison with age- and gender-matched controls. The peripheral anterior 6-12 mm annular corneal zone showed increased corneal densitometry in VKC cases compared to the healthy subjects. Additionally, the lens clarity is found to be decreased subclinically in VKC cases compared to control cases.

Is oxidative stress involved in vernal keratoconjunctivitis? Results from a pilot study in children.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a rare chronic conjunctivitis characterized by a predominantly eosinophil-mediated inflammatory disorder that could develop critical complications such as blindness. Oxidative stress plays a pivotal role in the pathogenesis of several allergic diseases. The role of oxidative stress has been hypothesized in VKC, but no study explored this issue. Furthermore, cyclosporine A (CsA) exerts an anti-inflammatory and antioxidant action on the conjunctiva. This study aimed to assess the oxidative stress in VKC patients and controls and to study the effect of CsA on oxidative stress in these subjects. METHODS: Thirty-six consecutive children, including 12 VKC (nine males, 75%; mean age 10.17; SD ± 2.48) patients without treatment, 12 VKC patients treated with CsA (nine males, 75%; mean age 9.08; SD ± 2.75), and 12 controls (CT) (seven males, 58%; mean age 8.58; SD ± 1.78), were recruited. A cross-sectional study was performed to compare H2 O2 in the serum with that in the tears of these children. RESULTS: Compared with CT and VKC children treated with CsA, VKC untreated children had significantly higher values of hydrogen peroxide (H2 O2 ) in the serum and the tears. No significant differences were observed between CT and VKC treated with CsA. A significant correlation was found at the linear regression analysis between serum and tear H2 O2 levels. CONCLUSION: This study provides the first report attesting that patients with VKC have high oxidative stress; furthermore, it suggests that CsA could have an anti-inflammatory and antioxidant action that could be useful to prevent the poor VKC outcome.

Japanese guidelines for allergic conjunctival diseases 2020.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease 2019. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.

Epidemiological aspects of allergic conjunctivitis.

The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases.

Complications of accelerated corneal collagen cross-linking: review of 2025 eyes.

PURPOSE: To evaluate the early- and late-stage complications of accelerated cross-linking (A-CXL) in a large case series and investigate the relationship of A-CXL complications with ocular and systemic conditions accompanying keratoconus. METHODS: Retrospectively, records of 2025 eyes of 1184 patients diagnosed with keratoconus between March 2013 and 2020 who underwent A-CXL (18 mW/cm2 for 5 min) treatment were reviewed. Comorbid ocular and systemic diseases other than keratoconus were recorded. In the postoperative follow-up, early and late complications and their association with accompanying diseases were examined. RESULTS: The mean age of patients was 26.16 ± 6.05 (range 18-42), and the mean follow-up time was 3.40 ± 1.63 years (range 1-8 years). Vernal keratoconjunctivitis (3.7%) was the most common disease accompanying keratoconus. Less frequently, systemic allergic diseases (2.9%) and Down syndrome (2.3%) were observed. The most common complication in the early postoperative period was haze formation (9.1%), while failure of the treatment (4.2%) occurred in the late period. Other common complications were loss of two or more Snellen lines (2.4%) and delayed epithelial healing (1.8%). There was a significant relationship between vernal keratoconjunctivitis and delayed epithelial healing (p = 0.011). Statistically significant relationships were found between Down syndrome and haze formation (p < 0.001) and sterile infiltrate formation (p = 0.041). CONCLUSION: Although A-CXL complication rates are low, vernal keratoconjunctivitis following A-CXL might increase the risk of delayed epithelial healing, and similarly corneal haze and sterile infiltrates might be observed more frequently in patients with Down syndrome.