The new preservative-free ophthalmic formulation of bilastine 0.6% preserves the ocular surface epithelial integrity in a comparative in vitro study.

Allergic conjunctivitis (AC) is the most common form of allergic eye disease and an increasingly prevalent condition. Topical eye drop treatments are the usual approach for managing AC, although their impact on the ocular surface is not frequently investigated. The aim of this study was to perform a comparative physicochemical characterization, and in vitro biological evaluations in primary conjunctival and corneal epithelial cells of the new multidose preservative-free bilastine 0.6% and main commercially available eye drops. MTT assay was used to measure cell viability; oxidative stress was analyzed with a ROS-sensitive probe; and apoptosis was evaluated monitoring caspase 3/7 activation. Differences in pH value, osmolarity, viscosity and phosphate levels were identified. Among all formulations, bilastine exhibited pH, osmolarity and viscosity values closer to tear film (7.4, 300 mOsm/l and ~ 1.5-10 mPa·s, respectively), and was the only phosphates-free solution. Single-dose ketotifen did not induce ROS production, and single-dose azelastine and bilastine only induced a mild increase. Bilastine and single-dose ketotifen and azelastine showed high survival rates attributable to the absence of preservative in its formulation, not inducing caspase-3/7-mediated apoptosis after 24 h. Our findings support the use of the new bilastine 0.6% for treating patients with AC to preserve and maintain the integrity of the ocular surface.

Exploration of efficacy and mechanism of 0.05% cyclosporine eye drops (II) monotherapy in allergic conjunctivitis-associated dry eye.

PURPOSE: To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE). METHODS: Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay. RESULTS: The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P < 0.050). And its improvement in itching scores (P7th < 0.001, P30th = 0.039, and P60th = 0.031) and TBUT (P7th = 0.009, P30th = 0.003, and P60th = 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P < 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores. CONCLUSIONS: 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching.

Subconjunctival injection of human umbilical cord mesenchymal stem cells alleviates experimental allergic conjunctivitis via regulating T cell response.

BACKGROUND: T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC). METHODS: A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 106 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells. RESULTS: Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice. CONCLUSIONS: Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.

Intense Pulsed Light Attenuates Oxidative Stress in Perennial Allergic Conjunctivitis.

Objective: To assess the effects of intense pulsed light (IPL) on oxidative stress (OS) in perennial allergic conjunctivitis (PAC). Background: IPL treatment has been proven effective for dry eye disease (DED). However, we have observed that, after IPL treatment, some patients with DED combined with allergic conjunctivitis (AC), an immune response condition in which excessive OS causes and exacerbates inflammatory damage, not only show an improvement in eye dryness, but also their AC-related eye itching is relieved. The mechanism by which IPL inhibits allergic reactions is not clear. Methods: Five patients with moderate-to-severe PAC were given two IPL treatments on the periorbital skin with a 2-week interval. Visual analog scale (VAS) scores and signs of AC, including eye redness and conjunctival follicles, were assessed before the first treatment (day 1) and 2 weeks after the second treatment (day 30). Tears were also collected at the same time, and lipid oxidation (LPO) metabolite analysis was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to investigate the effects of IPL on OS response. Results: The average VAS score significantly decreased with treatment (30.2 for day 1, 10.6 for day 30; p < 0.001). The general signs of PAC showed no difference (p > 0.05). LPO metabolite analysis revealed that 17,18-diHETE, which is an oxidation product of eicosapentaenoic acid, and 13-OXoODE, which is an oxidation product of linoleic acid, are significantly downregulated after IPL treatment. Conclusions: The photothermal effect of IPL attenuates OS in PAC, and this seems to be one of the mechanisms by which IPL treatment improves PAC. Clinical Trial Registration number: ChiCTR1900022202.

Topical cyclosporine versus allergen specific immunotherapy in perennial allergic conjunctivitis.

PURPOSE: Symptom control in the long-term with less side effects is important in perennial allergic conjunctivitis, since would improve quality of life. This study aimed to assess the clinical efficacies of topical cyclosporin A and subcutaneous allergen immunotherapy (SCIT) in terms of sign control in perennial allergic conjunctivitis. METHODS: This retrospective study included 20 adult patients with perennial allergic conjunctivitis and confirmed sensitization to house dust mites with skin prick test. Patients were assigned to either topical cyclosporine A treatment or SCIT. The participants were followed for 6 months, and signs scores were recorded at 1, 3 and 6 months. RESULTS: Overall, both cyclosporine and immunotherapy groups showed significant improvements in papillary reaction (p = 0.011 and 0.003, respectively), limbal involvement (p = 0.031 and 0.001), and conjunctival hyperemia (p = 0.001 and p < 0.001) scores during the 6-month follow-up. However, only cyclosporine group showed a significant improvement in corneal involvement scores (p = 0.015) during the study period. When scores at different time points were compared, significant improvement in conjunctival hyperemia was evident at 6 months in both groups when compared to baseline (cyclosporine group, 0.7 ± 0.68 vs. 2.4 ± 0.84, 70.8% decrease, p = 0.01; immunotherapy group, 0.3 ± 0.48 vs. 2.3 ± 0.95, 87.0% decrease, p = 0.004), whereas for limbal involvement such an improvement was only evident in the immunotherapy group (0.1 ± 0.32 vs. 1.3 ± 0.95, 92.3% decrease, p = 0.01). CONCLUSIONS: Allergen immunotherapy and cyclosporin A treatment may provide effective sign relief in perennial allergic conjunctivitis. It may represent an encouraging treatment option particularly for cases with perennial allergic conjunctivitis refractive to other treatments and positive skin prick test to a specific allergen (house dust in the present study). Long-term relief by SCIT would reduce the side effects of polypharmacotherapy. Larger studies with longer follow-up are warranted to confirm our findings.

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.

Long-term outcomes and risk factors for failure of glaucoma filtering surgery in eyes with vernal keratoconjunctivitis and steroid-induced glaucoma.

PURPOSE: To report outcomes and assess the risk factors for failure of trabeculectomy (trab), trabeculectomy with mitomycin-C (trabMMC), and combined trabeculectomy with cataract extraction (CT) in vernal keratoconjunctivitis (VKC) eyes with steroid-induced glaucoma (SIG). METHODS: Trab was performed in 45 eyes of 30 subjects, trabMMC in 36 eyes of 25 subjects, and CT in 34 eyes of 27 subjects. Success was complete when intraocular pressure (IOP) was between 6 and 21 mm Hg without anti-glaucoma medications (AGM) and qualified with AGM. RESULTS: Median age (14 vs. 16.3 and 17.4 years) was significantly less in the trab cohort (P = 0.007). Majority (88%-93%) were male (P = 0.78). Preoperatively, median duration of steroid usage was >2 years (P = 0.52), mean IOP (32, 29.4, and 28.4; P = 0.26) and median cup:disc ratio (CDR) (0.9; P = 0.27) were similar in the three groups. Complete success (76%, 71%, and 66% at 5 years; P = 0.91), and qualified success (88%, 97%, and 94% at 5 years; P = 1.0) with trab, trabMMC, and CT, respectively, were similar. Preoperative factors significantly associated with qualified failure (multiple logistic regression) were older children, longer duration of VKC, longer duration and mixed type of steroid use (all P < 0.001) and larger CDR (P < 0.02). At the last follow-up, 38% in trab, 33% in trabMMC, and 50% eyes in CT were blind (visual acuity ≤20/400 and/or visual field ≤10°) due to glaucoma (P = 0.33). CONCLUSION: The surgical success for all three types of surgery was similar at 5-years. Chronic VKC and long-term steroid use were associated with surgical failure. The majority had advanced disease and a significant proportion were blind due to glaucoma.

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.

Ectoine in the Treatment of Irritations and Inflammations of the Eye Surface.

The ocular surface is facing various unspecific stress factors resulting in irritation and inflammation of the epithelia, causing discomfort to the patients. Ectoine is a bacteria-derived extremolyte with the ability to protect proteins and biological membranes from damage caused by extreme environmental conditions like heat, UV-light, high osmolarity, or dryness. Evidence from preclinical and clinical studies attest its effectiveness in treating several epithelium-associated inflammatory diseases, including the eye surface. In this review, we analysed 16 recent clinical trials investigating ectoine eye drops in patients with allergic conjunctivitis or with other unspecific ocular inflammations caused by e.g. ophthalmic surgery. Findings from these studies were reviewed in context with other published work on ectoine. In summary, patients with irritations and unspecific inflammations of the ocular surface have been treated successfully with ectoine-containing eye drops. In these patients, significant improvement was observed in ocular symptoms of allergic rhinoconjunctivitis, postoperative secondary dry eye syndrome, or ocular reepithelisation after surgery. Using ectoine as an add-on therapy to antihistamines, in allergy patients accelerated symptom relief by days, and its use as an add-on to antibiotics resulted in faster wound closure. Ectoine is a natural substance with an excellent tolerability and safety profile thus representing a helpful alternative for patients with inflammatory irritation of the ocular surface, who wish to avoid local reactions and side effects associated with pharmacological therapies or wish to increase the efficacy of standard treatment regimen.

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.

Tofacitinib suppresses mast cell degranulation and attenuates experimental allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC), a common eye inflammation that affects patients' health and quality of life, is still a therapeutic challenge for ophthalmologists. Tofacitinib, a new Janus kinase (JAK) inhibitor, has been successfully used in the treatment of several disorders. Nonetheless, its effect in AC and the potential anti-allergic mechanisms are still unclear. The objective of the current study was to explore the roles of tofacitinib in preventing AC and elucidate the potential underlying mechanisms. METHODS: Tofacitinib was used topically in BALB/c mice with experimental allergic conjunctivitis (EAC). Ocular allergic symptoms and biological modifications were examined. To assess the anti-allergic mechanisms of tofacitinib, RBL-2H3 cells and HUVECs were cultured in vitro. The inhibitory effects and mechanisms of tofacitinib were studied and measured by real-time quantitative PCR, ELISA, western blot analysis, and flow cytometry. RESULTS: Topical administration of tofacitinib reduced the clinical symptoms of OVA-induced EAC, with a substantial mitigation in inflammatory cell infiltration, histamine release, and TNF-α mRNA as well as IL-4 mRNA expression. In vitro, tofacitinib repressed the degranulation and cytokine production in RBL-2H3 cells and reduced histamine-induced vascular hyperpermeability. The underlying mechanism might involve the downregulation of phosphorylation of JAK3/STATs signaling molecules in RBL-2H3 cells and HUVECs. CONCLUSIONS: Our findings provide evidence that tofacitinib prevented EAC by targeting the JAK3/STATs pathway. We recommend the use of tofacitinib as an innovative approach for the treatment of AC.

Novel Polyvinyl Pyrrolidone-Loaded Olopatadine HCl-Laden Doughnut Contact Lens to Treat Allergic Conjunctivitis.

Olopatadine HCl is an antiallergic drug used for the management of allergic conjunctivitis. Currently, it is delivered via eye drop solution, which is highly inefficient due to low bioavailability. Silicone contact lenses can be used to sustain the release of ophthalmic drugs. However, the presence of drug alters the optical transmittance and physical properties of the contact lens. The objective was to design a novel polyvinyl pyrrolidone (PVP)-coated olopatadine-ethyl cellulose microparticles-laden doughnut contact lens to sustained ocular delivery with limited alteration to the optical and swelling properties of the contact lens. The doughnut was implanted within the periphery of the lens using modified casting technique. Olopatadine HCl was loaded by soaking (SM-OL), direct loading (DL-OL), and doughnut casting method (DNT-OL). PVP (comfort agent) was loaded on the surface of contact lens for all the batches via novel curing technique. The in vitro olopatadine HCl release data of SM-OL (up to 48-72 h) and DL-OL batches (up to 72 h) showed high burst release, whereas DNT-OL batch showed sustained release up to 120 h without significant (p > 0.05) alteration in the optical and swelling properties of contact lens. All the batches showed sustained release of PVP up to 120 h. The in vivo studies in the rabbit tear fluid showed improvement in the olopatadine HCl and PVP retention time in comparison to eye drop solution. The PVP-loaded DNT-OL-500 lens showed tear stabilization (comfort wear) in Schirmer strip test (rabbits) with no protein adherence in comparison to DNT-OL-500 lens without PVP. The study demonstrated the successful delivery of olopatadine HCl and PVP-K30 from the doughnut contact lens for the extended period with limited alteration to the optical and swelling properties of contact lens.

Steroid-induced glaucoma and blindness in vernal keratoconjunctivitis.

PURPOSE: To report the clinical features, treatment outcomes and blindness associated with steroid-induced glaucoma in vernal keratoconjunctivitis (VKC). MATERIALS AND METHODS: Records of patients with VKC, who visited our tertiary centre from 1992 and 2009, were reviewed and those with steroid-induced glaucoma were included in the study. Glaucoma was diagnosed based on intraocular pressure (IOP) ≥22 mm Hg on two consecutive visits (ocular hypertension) and/or glaucomatous optic disc damage. Blindness was defined as best corrected visual acuity of ≤20/400 or visual field <10°. RESULTS: Of the 4062 VKC subjects, 91 (157 eyes) had steroid-induced glaucoma (SIG), showing a prevalence of 2.24%. Of these 87% were men. The median (IQR) age at onset of VKC was 12 years (7-17). At presentation, the median duration of VKC was 48 months (24-72) and the median duration of steroid usage was 24 months (12-36). The median cup-to-disc ratio (CDR) was 0.9 (0.7-0.9) and median mean deviation was -21.9 dB (-30.0 to -10.2). IOP was medically controlled in 66% eyes (104/157) and 34% eyes (53/157) needed glaucoma surgery. High presenting IOP (OR: 1.04; p=0.05) and increased duration of steroid usage (OR: 1.07; p=0.02) were significantly associated with need for glaucoma surgery. At presentation, 29/91 subjects (31.8%) were bilaterally blind due to SIG. Higher CDR at presentation was significantly associated with blindness in this cohort (p=0.02). CONCLUSION: In this cohort of VKC with SIG, the disease predominantly affected adolescent males. Glaucoma was severe with one-third needing surgery and one-third blind due to SIG.

Effects of Docosahexaenoic Acid on Chemokine Expression in Human Conjunctival Fibroblasts.

Purpose: We assessed the production of chemokines by human conjunctival fibroblasts in response to inflammation and the effects of omega (ω)-3 fatty acids on chemokine expression.Methods: Primary cultures of human conjunctival fibroblasts were incubated with interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α). The expression of eotaxin-1 and RANTES in response to pretreatment with docosahexaenoic acid (DHA) was investigated. Moreover, western blotting was used to evaluate the effects of DHA on the activation of nuclear factor (NF)-κB and signal transducer and activator of transcription 6 (STAT6).Results: The expression of eotaxin-1 mRNA was significantly suppressed by pretreatment with DHA with IL-4 and TNF-α costimulation. RANTES expression was similarly suppressed, but the difference was not significant. The secretion of eotaxin-1 and RANTES was significantly lower in DHA-pretreated cells than in vehicle-treated cells. Western blotting for NF-κB and STAT6 showed that these proteins were downregulated in the DHA pretreatment group compared with those in the vehicle control group.Conclusion: The results of this study suggested that DHA could have applications in the management of allergic inflammation.

Gonioscopy-assisted Transluminal Trabeculotomy in a Pediatric Patient With Steroid-induced Glaucoma.

PURPOSE: To report a case of successful intraocular pressure (IOP) reduction after a 360-degree gonioscopy-assisted transluminal trabeculotomy (GATT) using the iTrack catheter in a patient with steroid-induced glaucoma as a result of treatment of vernal keratoconjunctivitis (VKC). MATERIALS AND METHODS: Case report. RESULTS: An 8-year-old male individual with a long-standing history of VKC, treated with topical steroids, developed elevated IOP and glaucoma in the right eye despite maximum topical glaucoma therapy. Reducing the steroid was not a viable option given the severity of VKC. A 360-degree GATT was successfully performed and IOP has been maintained off all glaucoma drops. CONCLUSIONS: GATT is a viable option for steroid-induced glaucoma in the pediatric population. This obviates the need for riskier, more invasive conjunctival-based procedures.

Safety and Efficacy of Corneal Cross-linking in Pediatric Patients with Keratoconus and Vernal Keratoconjunctivitis.

PURPOSE: The purpose of the study is to determine the safety and efficacy of corneal collagen cross-linking for keratoconus in pediatric patients with and without vernal keratoconjunctivitis (VKC). METHODS: This is a retrospective analysis of 89 eyes of 58 patients <18 years of age that underwent corneal collagen cross-linking for progressive keratoconus; inclusion criteria included a minimum of 2-year follow-up after cross-linking. The main outcomes measures included keratometry, pachymetry, vision, and complications following epithelial-off cross-linking with the Dresden protocol. RESULTS: VKC patients were more likely to be male; 81.6% of the non-VKC patients and 96.3% of VKC patients were male (P = 0.038). Comparing pretreatment to the 2-year follow-up, there was no statistically significant change in the mean steep or flat keratometry, corneal thickness, and uncorrected visual acuity or best spectacle-corrected visual acuity in either group. There were no statistically significant differences in the mean visual, keratometric, or adverse event outcomes between the two groups. The proportion exhibiting progression of ectasia at 2 years was 18.5% in the VKC group and 16.7% in the non-VKC group (P = 0.83). CONCLUSIONS: Cross-linking appears to be as safe and effective in pediatric patients with vernal keratoconjunctivits as in those without, with similar outcomes, adverse events, and progression of keratoconus after treatment. The proportion of patients exhibiting progression appears to be higher in pediatric patients than adults, and there is an association between male sex and diagnosis of VKC.

IgE-Mediated Multimorbidities in Allergic Asthma and the Potential for Omalizumab Therapy.

Allergic asthma often coexists with different pathological conditions, called multimorbidities, that are mostly of allergic nature and share a common underlying inflammatory pathophysiological mechanism. Multimorbidities of allergic asthma may influence asthma control, its severity, and patients' response to treatment, and contribute to the overall socioeconomic burden of the disease. Immunoglobulin E (IgE) is known to play a central role in the pathogenesis of various allergic diseases, including asthma. Thus, IgE-mediated immunologic pathways present an attractive target for intervention in asthma and multimorbidities. In this review, we discuss the most frequently reported IgE-mediated multimorbidities in allergic asthma, including allergic rhinitis, rhinoconjunctivitis, atopic dermatitis, vernal keratoconjunctivitis, chronic rhinosinusitis with nasal polyps, food allergies, and allergic bronchopulmonary aspergillosis. Omalizumab is a recombinant humanized monoclonal antibody against IgE and has been in use to treat allergic asthma for more than a decade. We comprehensively review the clinical evidence for omalizumab in the treatment of the aforementioned multimorbidities in allergic asthma.

Long-term use of topical tacrolimus ointment: a safe and effective option for the treatment of vernal keratoconjunctivitis / Uso prolongado de tacrolimus tópico: opção eficaz e segura no tratamento da ceratoconjuntivite vernal

ABSTRACT Purpose: To assess the compliance, efficacy, and safety of the long-term use of topical tacrolimus for the clinical management of vernal keratoconjunctivitis. Methods: The medical records of patients with vernal keratoconjunctivitis undergoing long-term treatment with 0.03% topical tacrolimus were retrospectively reviewed. The duration of tacrolimus use and the causes for drug discontinuation were used to assess treatment compliance. To assess drug efficacy, the need for and the number of times that topical corticosteroids were used to control symptoms were registered. Side effects related to tacrolimus use were monitored to determine drug safety. Results: The study cohort consisted of 21 patients who met the eligibility criteria. The mean duration of tacrolimus use was 41.3 ± 18.5 months. Fourteen patients (66.7%) continuously used tacrolimus, and three (14.3%) discontinued treatment following complete remission. Four patients (19%) did not use tacrolimus as prescribed or interrupted tacrolimus use on their own: two (9.5%) because of discomfort upon application and two (9.5%) because of the lack of improvement. Ten patients (47.6%) maintained disease control without the use of corticosteroids, whereas 11 (52.4%) required an average of 2.70 ± 1.35 corticosteroid cycles to control symptoms. The only reported side effect was discomfort upon application. Conclusions: Despite the small sample size and study design limitations, these results support the long-term use of topical tacrolimus as an effective and safe option for the treatment of vernal keratoconjunctivitis, with good compliance of patients to the treatment.

RESUMO Objetivo: Avaliar a aderência, a eficácia e segurança do uso prolongado de tacrolimus tópico no controle clínico da ceratoconjuntivite vernal. Métodos: Um estudo retrospectivo foi desenvolvido através da análise de prontuários de pacientes com ceratoconjuntivite vernal em tratamento prolongado com tacrolimus tópico 0,03%. A duração do tempo de uso do ta­crolimus e as causas de descontinuação da medicação foram usadas para avaliar a adesão ao tratamento. Para avaliar a eficácia da droga, a necessidade e o número de vezes em que corticoides tópicos foram utilizados para controlar os sintomas foram registrados. Os efeitos colaterais relacionados ao uso do tacrolimus foram monitorados para determinar a segurança da droga. Resultados: Vinte e um pacientes preencheram os critérios de eleição e foram incluídos no estudo. A duração média do uso de tacrolimus foi de 41,3 ± 18,5 meses. Quatorze pacientes (66,7%) usaram continuamente o tacrolimus e 3 (14,3%) descontinuaram o tratamento após a remissão completa. Quatro pacientes (19%) não usaram o tacrolimus conforme prescrito ou interromperam o uso da droga isoladamente: 2 (9,5%) por desconforto na aplicação e 2 (9,5%) pela falta de melhora. Dez pacientes (47,6%) mantiveram a doença sob controle sem o uso de corticoides, enquanto 11 (52,4%) necessitaram em média 2,70 ± 1,35 ciclos corticoides para controle dos sintomas. O único efeito adverso relatado foi desconforto na aplicação. Conclusões: Apesar do pequeno tamanho da amostra e das limitações do desenho do estudo, esses resultados suportam o uso prolongado do tacrolimus tópico como opção eficaz e segura para o tratamento da ceratoconjuntivite vernal, com boa adesão dos pacientes ao tratamento.

Immunopathological Features of Severe Chronic Atopic Keratoconjunctivitis and Effects of Topical Cyclosporine Treatment.

PURPOSE: To assess differential roles of inflammatory cells in pathophysiology of severe atopic keratoconjunctivitis (AKC) and evaluate immunomodulatory effects of topical cyclosporine A (CsA). METHODS: A total of 10 patients with severe, steroid-dependent/resistant chronic active AKC were treated using frequent topical CsA 0.05% as monotherapy for 2 months. Conjunctival biopsy specimens before and after treatment were examined using immunohistochemistry. A total of 10 healthy age-matched adults served as the control group. RESULTS: Baseline AKC samples revealed greater cluster of differentiation 4 (CD4), interferon gamma (IFNγ), human leukocyte antigen-D-related (HLA-DR) positive cell densities compared with healthy controls (P < 0.05), as well as interleukin (IL)-17 (P = 0.08). Topical CsA treatment induced a significant reduction in CD4 and IL-17 expressions (P < 0.05); post-treatment levels were same as normals (P > 0.05). Despite reduction after treatment (P = 0.06), HLA-DR expression remained higher than controls (P < 0.05). CONCLUSIONS: AKC-related conjunctival inflammation appears to be mediated by delayed hypersensitivity. In this short-term trial, frequent topical CsA improved conjunctival inflammation.

Vernal Keratoconjunctivitis.

Vernal keratoconjunctivitis, a chronic bilateral seasonal allergic inflammatory disease of the eye, is an important cause of visual debilitation and impairment of quality of life in children and young adults in certain parts of the world such as the Mediterranean areas, Central and West Africa, the Middle East, Japan, the Indian subcontinent, and South America. It usually has a self-limiting course; however, in a few cases, the disease is recurrent and leads to long-term visual disabling complications such as keratoconus and limbal stem cell deficiency. The main pathogenic mechanism is immunoglobulin E mediated; however, there may be non-immunoglobulin E and certain nonspecific hypersensitivity mechanisms. The predominant cell types involved are CD4 T cells and eosinophils. The management of vernal keratoconjunctivitis is challenging. Although an acute episode can be well managed with the help of currently available topical agents, the major challenge lies in preventing recurrences and their consequences. Steroids are highly effective in controlling both an acute episode and chronic disease; however, the long-term complications of steroid use often prevent their continued use. Immunomodulators such as tacrolimus and cyclosporine may be used as steroid-sparing agents; however, the dosing and duration of use still need to be clearly defined. Surgery is required for the management of complications such as shield ulcer and corneal ectasia or opacity; however, the disease process and management are largely well defined, and genetic predisposition factors responsible for chronicity and an effective albeit safe treatment modality for the chronic form of the disease need further research.