Ocular Inflammatory Conditions Research Articles

RETRACTED ARTICLE: Cystoid Macular Oedema in a Patient Treated with STING Agonist and Ezabenlimab for Disseminated Melanoma.

We describe a case of cystoid macular oedema associated with combination treatment using a STING agonist and ezabenlimab for disseminated melanoma. A 66-year-old male patient presented with worsening vision and cystoid macular oedema in the right eye, along with a small accumulation of subretinal fluid in the left eye. The patient has been undergoing treatment for melanoma since 2014. Five months prior to the ocular presentation, the patient was enrolled in a first-in-human trial with a STING agonist and ezabenlimab. Topical treatment with dexamethasone 0.1% drops and ketorolac 0.5% drops was prescribed, and he continued with systemic immunotherapy. After 6 weeks, morphological and functional improvement was noted; however, cystoid macular oedema persisted. Consequently, systemic immunotherapy was temporarily suspended. After an additional 4 weeks, cystoid macular oedema regressed in the right eye and subretinal fluid completely resolved in the left eye. In the first-in-human trial with a STING agonist and ezabenlimab for melanoma, cystoid macular oedema emerged as a notable ocular side effect with vision worsening. This case highlights the importance of careful ocular monitoring in patients receiving this combination therapy. The cGAS-STING pathway is an important target for future research in treating ocular inflammatory conditions.

Evaluation of drug release, mucoadhesive and viscoelastic performances of Netildex gel versus an antibiotic‐steroid combination system

Purpose: The poor bioavailability and therapeutic response exhibited by conventional antibiotic‐steroid ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome using a gel systems. Netildex gel is a preservative‐free product based on netilmicin and dexamethasone indicated for the treatment of inflammatory ocular conditions of the anterior segment and ocular adnexa including post‐cataract surgery. The current investigation evaluated the in vitro drug release, viscosity and mucoadhesion profile of Netildex gel in comparison to a gel matrix with regard to steroid and antibiotic delivery.Methods: In vitro drug release was assessed using Franz‐type diffusion cells, under sink condition, exploiting a simulated tear solution (STS) as dissolution medium and a regenerated cellulose membrane. Evaluation of mucoadhesive and viscoelastic properties were performed by texture analyzer TA‐XT2 and rheometer.Results: The dexamethasone and netilmicin release curves in Netildex gel exhibited a better sustained and controlled pattern over an extended time period (48 h) with respect to another gel system containing anti‐inflammatory and antibiotic drugs. The results were expressed as cumulative percentage of drug release and the antibiotics‐release kinetics from the polymeric matrix, evaluated by different mathematical models. The determination of detachment force demonstrated a significant mucoadhesive strength of Netildex gel compared to mucin. Moreover, rheological analysis of Netildex gel highlighted a strong pseudo‐plastic behaviour under shear strain due to its formulation features.Conclusions: Overall, Netildex gel exhibits a sustained and controlled drug release of both dexamethasone and netilmicin from polymeric matrix thanks to its viscoelastic and mucoadhesive properties allowing to prolong drug residence time on the ocular surface. These data support the reduced administration frequency while maintaining the same efficacy and simultaneously favouring patients' compliance [1].Reference1. Mencucci R. et al. Adv Ther (2022) 39: 5474–5486.

Zapalenia przedniego odcinka oka w przebiegu łuszczycy

Psoriasis is a chronic, autoimmune, inflammatory skin disease affecting around 2–4% of the general population. Due to many comorbidities, i.e., cardiovascular diseases, nowadays is even perceived as a systemic illness. Ocular manifestations have an occurrence rate of 10–12% among patients diagnosed with psoriasis. This article presents the ocular anterior segment inflammatory conditions associated with psoriasis

Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease.

Uveitis is a complex ocular inflammatory disease with a multifactorial etiology that can result in blindness. Although corticosteroid eye drops are the primary treatment for anterior uveitis, their efficacy is limited by low bioavailability, adverse effects, and a narrow focus on inflammation. In this study, the multifunctional hydrogel eye drops (designated as DCFH) were developed by incorporating the anti-inflammatory agent dexamethasone (DSP) and reactive oxygen species (ROS) scavenger cerium-based metal-organic frameworks (Ce-MOFs) into thermosensitive triblock copolymer F127 for the synergistic treatment against uveitis. The resulting F127 eye drops offer a favorable alternative to ophthalmic solution due to its thermosensitivity, thixotropy, light transmittance, improved ocular bioavailability, and unexpected anti-inflammatory efficacy. Notably, the participation of nanoporous Ce-MOFs, functional drug carriers, not only reduces ROS level but also boosts the anti-inflammatory activity of DSP in vitro. Therapeutically, the multifunctional DCFH exhibits superior efficacy in treating endotoxin-induced uveitis by mitigating the ophthalmic inflammatory reaction, suppressing inflammatory cytokines (e.g., TNF-α, IL-6, and IL-17) and downregulating the expression of iNOS and NLPR3. This synergistic treatment provides a valuable and promising approach for the management of uveitis and other ocular inflammatory conditions.

Preparation and Characterization of Prednisolone Acetate Microemulsion for Ophthalmic Use

Background: Prednisolone acetate is an ester form of prednisolone. It is used topically as an ophthalmic suspension to treat many inflammatory ocular conditions, where its absorption from suspension is highly variable and has poor dose accuracy. Objectives: The main objective of this research is to formulate and evaluate prednisolone acetate microemulsion for ophthalmic use to increase solubility, residence time, and corneal permeability of the drug to enhance patient compliance and treatment efficacy. Methods: Twenty-four prednisolone acetate-loaded microemulsion (0.5%w/w) formulas were prepared using oleic acid, isopropyl myristate as (oil phase) (1:1), tween 80, labrasol, and cremophor EL as (surfactant), ethanol, polyethylene glycol 400, propylene glycol, transcutol P as co-surfactant and Sörensen isotonic phosphate buffer saline pH 7.4 as the aqueous phase at different Smix ratios (1:1), (1:2) and (2:1) by aqueous titration method to construct pseudoternary phase diagram to determine the existence of microemulsion region. All the prepared formulas were subjected to different evaluation tests to determine the optimum formula. Results: observations of the microemulsion showed that it had a clear and transparent yellowish color, formulation F9 composed of oleic acid and isopropyl myristate in a ratio (1:1) as oil, twee80 as a surfactant, and propylene glycol: ethanol (1:1) in a ratio (2:1) as cosurfactant gave the best particle size (10.18nm), polydispersity index (0.2216), zeta potential (-25,91), % of transmittance (99.382%±0. 09), and drug content (100±0.16). Microemulsion formulation provided considerably higher permeability than the marketed eye drop suspension (Optipred®) and improved bioavailability. Conclusions: The microemulsion-containing prednisolone acetate is a promising ocular carrier for the controlled release of prednisolone acetate in treating anterior segment inflammation. Received: Dec. 2022 Accepted March 2023 Published: Oct.2023

Comprehensive Assessment of Transcorneal Permeation, Antimicrobial, and Antifungal Activities of Andrographolide-Loaded Nanosuspension: In vitro and In vivo Studies

This study aimed to comprehensively assess the transcorneal permeation, antimicrobial, and antifungal activities of a nanosuspension loaded with Andrographolide, a promising herbal compound. Through a combination of in vitro and in vivo studies, the efficacy, and potential applications of the nanosuspension in ocular drug delivery were investigated. In the in vitro phase, transcorneal permeation studies were conducted using Franz diffusion cells with excised rabbit corneas. The nanosuspension demonstrated significantly enhanced permeation compared to a control formulation, indicating its ability to effectively deliver Andrographolide through the cornea and into the ocular tissues. Additionally, the nanosuspension exhibited potent antimicrobial and antifungal activities against various ocular pathogens, as determined by agar diffusion and broth microdilution assays. Building upon the promising in vitro results, in vivo studies were performed using a rabbit model. Ocular tolerability of the nanosuspension was assessed through eye observations, with no observed signs of irritation or adverse effects. Furthermore, the nanosuspension's in vivo antimicrobial and antifungal activities were evaluated by instilling the formulation into the rabbits' eyes and monitoring conjunctival congestion and inflammation. The results demonstrated a significant reduction in conjunctival congestion, highlighting the nanosuspension's potential for combating ocular infections and inflammation. The comprehensive assessment presented in this study establishes the transcorneal permeation capability of the Andrographolide-loaded nanosuspension and its remarkable antimicrobial and antifungal activities. These findings underscore the potential of the nanosuspension as an effective ocular drug delivery system for various ocular infections and inflammatory conditions. The study contributes to the development of novel therapeutic approaches in ophthalmology, aiming to improve patient outcomes and provide alternative treatment options for ocular diseases.
 Keywords: Transcorneal permeation; Nanosuspension; Andrographolide; Antimicrobial activity; Antifungal activity; Ocular drug delivery

Binary Polymeric Surfactant Mixtures for the Development of Novel Loteprednol Etabonate Nanomicellar Eyedrops.

The treatment of several ocular inflammatory conditions affecting different areas of the ocular globe involves the administration of topical ophthalmic formulations containing corticosteroids. This research was aimed at evaluating the solubilising efficacy of 5.0% w/w of different binary mixtures of commercial amphiphilic polymeric surfactants with the purpose of obtaining nanomicellar solutions containing a high amount of loteprednol etabonate (LE). The selected LE-TPGS/HS nanomicelles, containing 0.253 mg/mL of the drug, had a small size (=13.57 nm) and uniform distribution (Polydispersity Index = 0.271), appeared completely transparent and perfectly filterable through 0.2 μm membrane filter, and remained stable up to 30 days at 4 °C. The critical micellar concentration (CMCTPGS/HS) was 0.0983 mM and the negative value of the interaction parameter between the polymeric-surfactant-building unit (βTPGS/HS = -0.1322) confirmed the ability of the polymeric surfactants to interact, favouring the dissolution of LE into nanomicelles. The disappearance of the endothermic peak of LE in the DSC analysis confirmed the interactions of LE with the polymeric surfactants. LE-TPGS/HS produced in vitro LE which sustained diffusion for 44 h (more than 40% of encapsulated LE). Furthermore, the lack of a significant cytotoxic effect on a sensitive corneal epithelial cell line makes it a candidate for further biological studies.

Acute Syphilitic Posterior Placoid Chorioretinitis; a Case Report and Review

Background: Acute syphilitic posterior placoid chorioretinopathy (ASPPC) is a rare but defining characteristic of ocular syphilis. Clinical findings are subtle, geographic, yellowish, macular lesions, affecting the outer-retina and inner choroid, and often associated with subretinal fluid in the early phase. This case report will review the clinical signs of ASPPC to aid the practitioner in identification and recognition of its clinical importance as it relates to early diagnosis, treatment, and prognosis. Case Report: A 79-year-old African American male presented to clinic with a chief complaint of blur in the right eye for the prior two days. Spectral Domain Optical Coherence Tomography (SD-OCT) of the macula revealed a shallow retinal pigment epithelial detachment with subretinal fluid centrally with some loss of the retinal pigment epithelium (RPE) and photoreceptors nasally in the right eye. There was rapid progression over a week to full loss of RPE and photoreceptors with reduction of vision to hand motion in the right eye, suggesting an infectious etiology. Serologic testing was ordered, and an RPR and FTA-ABS were both reactive. A diagnosis of acute syphilitic posterior placoid chorioretinopathy was made. An infectious disease physician treated the patient with IV penicillin G. There was a complete resolution of ocular findings. Conclusion: Syphilis should be considered for any ocular inflammatory condition. ASPPC is highly suggestive of syphilis. All patients with ocular syphilis should be evaluated for neurosyphilis. Treatment is IV penicillin G for 10-14 days and considered successful when there is a four-fold reduction in titers. Full visual recovery typically occurs within 12 weeks of treatment if a diagnosis and treatment are initiated early in the course of ocular disease.

Ocular surface immune cell diversity in dry eye disease.

Dry eye disease (DED) is a multifactorial chronic ocular surface inflammatory condition. Disease severity has been directly related to the immuno-inflammatory status of the ocular surface. Any perturbation in the orchestrated functional harmony between the ocular surface structural cells and immune cells, both resident and trafficking ones, can adversely affect ocular surface health. The diversity and contribution of ocular surface immune cells in DED have been of interest for over a couple of decades. As is true with any mucosal tissue, the ocular surface harbors a variety of immune cells of the innate-adaptive continuum and some of which are altered in DED. The current review curates and organizes the knowledge related to the ocular surface immune cell diversity in DED. Ten different major immune cell types and 21 immune cell subsets have been studied in the context of DED in human subjects and in animal models. The most pertinent observations are increased ocular surface proportions of neutrophils, dendritic cells, macrophages, and T cell subsets (CD4+; CD8+; Th17) along with a decrease in T regulatory cells. Some of these cells have demonstrated disease-causal association with ocular surface health parameters such as OSDI score, Schirmer's test-1, tear break-up time, and corneal staining. The review also summarizes various interventional strategies studied to modulate specific immune cell subsets and reduce DED severity. Further advancements would enable the use of ocular surface immune cell diversity, in patient stratification, i.e. DED-immunotypes, disease monitoring, and selective targeting to resolve the morbidity related to DED.

The role of a multicentre data repository in ocular inflammation: The Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS).

In the current literature, clinical registry cohorts related to ocular inflammation are few and far between, and there are none involving multi-continental international data. Many existing registries comprise administrative databases, data related to specific uveitic diseases, or are designed to address a particular clinical problem. The existing data, although useful and serving their intended purposes, are segmented and may not be sufficiently robust to design prognostication tools or draw epidemiological conclusions in the field of uveitis and ocular inflammation. To solve this, we have developed the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) Clinical Registry. OASIS collects prospective and retrospective data on patients with all types of ocular inflammatory conditions from centers all around the world. It is a primarily web-based platform with alternative offline modes of access. A comprehensive set of clinical data ranging from demographics, past medical history, clinical presentation, working diagnosis to visual outcomes are collected over a range of time points. Additionally, clinical images such as optical coherence tomography, fundus fluorescein angiography and indocyanine green angiography studies may be uploaded. Through the capturing of diverse, well-structured, and clinically meaningful data in a simplified and consistent fashion, OASIS will deliver a comprehensive and well organized data set ripe for data analysis. The applications of the registry are numerous, and include performing epidemiological analysis, monitoring drug side effects, and studying treatment safety efficacy. Furthermore, the data compiled in OASIS will be used to develop new classification and diagnostic systems, as well as treatment and prognostication guidelines for uveitis.

Demodicosis in Different Age Groups and Alternative Treatment Options—A Review

Infestation with Demodex mites is a common occurrence, especially in adults and the elderly. More recent attention has been paid to the presence of Demodex spp. mites in children, even ones without comorbidities. It causes both dermatological and ophthalmological problems. The presence of Demodex spp. is often asymptomatic, thus it is suggested to include parasitological investigation tests in dermatological diagnostics, in addition to bacteriological analysis. Literature reports show that Demodex spp. are related to the pathogenesis of numerous dermatoses, including rosacea or demodicosis gravis, and common eye pathologies reported by patients such as dry eye syndrome or ocular surface inflammatory conditions, such as blepharitis, chalazia, Meibomian gland dysfunction, and keratitis. Treatment of patients is a challenge and is usually prolonged, therefore it is important to carefully diagnose and properly select the therapy regimen for the treatment to be successful, and with minimal side effects, especially for young patients. Apart from the use of essential oils, research is ongoing for new alternative preparations active against Demodex sp. Our review was focused on the analysis of the current literature data on the available agents in the treatment of demodicosis in adults and children.

Adaptive Optics of Kyrieleis Plaques in Varicella Zoster Virus-Associated Posterior Uveitis: A Multimodal Imaging Analysis.

Kyrieleis plaques (KP) represent a peculiar type of vasculitis affecting retinal arterial branches in a beaded segmental pattern that can be found in several posterior inflammatory ocular conditions. The nature and precise location of KP is unclear. Adaptive Optics (AO) provides an in vivo visualization of retinal vasculature on a microscopic level, thus permitting a more detailed characterization of KP as compared to traditional imaging techniques. This study aims to report AO imaging of KP in Varicella Zoster virus (VZV)-associated posterior uveitis and to correlate the findings with traditional imaging techniques. Three patients diagnosed with VZV posterior uveitis underwent adaptive optics (AO) imaging and traditional multimodal imaging techniques, including fundus photography, fluorescein angiography, indocyanine green angiography and optical coherence tomography. In all subjects, AO imaging revealed segmental hyporeflectivity confined to the vessel wall, with no evidence of arterial wall disruption or extravascular involvement. In our series, AO findings support the view that KP are localized within the inner arterial wall, possibly at the endothelial level.

The Great Masquerader: A Clinical Case

Known as the ‘Great Imitator’, ocular syphilis often mimics a variety of ocular inflammatory conditions, and as such can pose a challenge to diagnosis. It is classically associated with secondary syphilis, however may present in all stages of disease. Presentations include scleritis, interstitial keratitis, iritis, chorioretinitis, papillitis, retinal vasculitis, exudative retinal detachment and optic and cranial neuropathies. Non-treponemal tests (VDRL, RPR) are used for screening and to monitor response to treatment, while treponemal tests (FTA-ABS, TPPA) are used for confirmation of diagnosis and remain positive for life.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Prospective observational study conducted between September 2016 and February 2020. Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Clinical features of inflammatory vitreous haemorrhage: A comparative study between children and adults

AbstractPurpose: To compare clinical findings and visual outcomes of vitreous haemorrhage (VH) associated with inflammatory ocular conditions between children and adults patients.Methods: Retrospective study including 46 patients (56 eyes) diagnosed with VH associated with inflammatory ocular conditions in Department of ophthalmology, Fattouma Bourguiba university hospital, Tunisia. Demographics, clinical findings, etiologies, treatment modalities, and visual outcomes were compared between adults and children. Mean follow‐up period was 18 months.Results: There were 10 children (12 eyes) and 36 adults (44 eyes) patients. Mean age was 9.5 years in the children group (six males and four females) and 35 years in the adult group (26 males and 10 females). Comparative study showed that VH in the paediatric group was associated with a significantly lower presenting visual acuity, more frequently vitritis and fern‐like capillaritis, whereas VH in the adult group were more associated with vascular sheathing and retinal haemorrhages. The main mechanism of bleeding was inflammatory optic disc neovessels (NV) in the children group (66.6%, p ≤ 0.001) and ischemic posterior segment NV in the adult group (81.8%, p ≤ 0.001). Idiopathic intermediate uveitis (40%) was the leading cause of VH in the children group. However, tuberculosis (41.7%), Behçet's (19.4%) disease and sarcoidosis (11.1%) were the most common etiologies in the adult group. The mean final visual acuity was significantly higher in the paediatric group (20/25) than the adult group (20/50) (p = 0.045).Conclusions: Inflammatory VH has a distinctive clinical and etiological profile between children and adults.

Microbiota in MGD

AbstractMGD is characterized by significant changes in meibum quality that may lead to the changes in the existing ocular surface flora that can contribute to the inflammatory state typical of the condition. Several papers have addressed this aspect. Li and coworkers, dividing the DE group into MGD and non‐MGD patients, found that no statistically significant differences between the two groups. 67 Pseudomonas, Bacillus, Acinetobacter and Corynebacterium were the most represented, although Bacilli showed a higher relative abundance in the MGD group and could be considered typical pathogens of MGD. Watters and colleagues studied patients with several degrees of MGD, among which CL wearers were included. Meibum expression did not modify the bacterial profile. CoNS were the most prevalent organisms isolated, present in two thirds of the population studied, although their presence was not correlated to the severity of MGD. CL wearers showed an increased presence of P. acnes that was correlated to MGD severity. No differences in microbiota were observed related to the severity of anterior blepharitis or CL wear. Dong and coworkers, using 16 S rDNA sequencing, investigated the microbiome of 47 Chinese MGD patients compared with a control group of 42 sex‐ and age‐matched subjects without MGD. They found significant differences at the phyla level, with a significantly higher abundance of Firmicutes (31.7% vs. 19.7%) and Proteobacteria (27.5% vs. 14.7%), and a lower abundance of Actinobacteria (34.2% vs. 57%) in MGD vs control patients. At the genus level, the numbers of Staphylococcus (20.7% vs. 7.9%) and Sphingomonas (5.7% vs. 0.8%) were significantly higher in patients with MGD vs controls, while the numbers of Corynebacterium (20.2% vs. 46.4%) were significantly lower. The meiboscores showed a significant direct correlation with the abundance of Staphylococcus in MGD patients. They concluded that patients with MGD can have bacterial microbiota alterations in the conjunctival sac, with a potential role of Staphylococcus, Corynebacterium and Sphingomonas sp. in MGD pathophysiology. In a previous study carried out on a small group of patients with blepharitis, Lee and coworkers demonstrated that blepharitis might be associated with a change in microbial composition, namely, greater quantities of Streptophyta, Corynebacterium and Enhydrobacter species. It was suggested that cytotoxicity and inflammatory components, triggered by bacterial growth, may contribute to the pathological process of MGD. Zheng et al confirmed the changes of ocular surface flora in MGD patients showing a wide bacterial profile and positive aerobic and anaerobic culture, significantly higher in both meibomian secretion and conjunctiva of MGD patients than in controls. The ocular surface inflammatory condition occurring in MGD and blepharitis could be mediated by the induced expression of acidic mammalian chitinase (AMCase) that is considered an immune response activator and is over expressed in MGD. It can be hypothesized that changes in ocular surface microbial flora can mediate AMCase upregulation.

Real-World Use of Loteprednol Etabonate 0.5%/Tobramycin 0.3% Ophthalmic Suspension for the Treatment of Ocular Surface Inflammatory Conditions.

Use of a combination corticosteroid/antibiotic product is common in ocular surface inflammatory conditions for which corticosteroid therapy is indicated and there exists a risk of superficial bacterial infection. Combination loteprednol etabonate 0.5% and tobramycin 0.3% (LE/T) has been evaluated for blepharokeratoconjunctivitis in two trials, but there has been limited reporting on its real-world use. This was a retrospective chart review conducted at three optometry practices in the USA. Data were collected from cases in which LE/T was used and data were recorded for the period commencing with therapy with a minimum of one follow-up visit (within 2 months). Data abstracted included patient demographics, diagnosis, LE/T dosing regimen, pre- and post-treatment ocular signs and symptoms, intraocular pressure (IOP) measurements, adverse event (AE) reports, visual acuity (VA), and any notations as to resolution of baseline condition. Primary outcomes of interest included IOP changes and AEs. Ninety-six patient charts were extracted, and data from 87 charts (115 LE/T-treated eyes) were included. Mean (SD) years of age was 45.6 (19.7), most patients were white (83.9%), and just over half were female (58.6%). Common baseline conditions were conjunctival injury/corneal abrasion (25.3%), keratitis (18.4%), viral conjunctivitis (16.1%), and blepharitis/eyelid inflammation/MGD (11.5%). The most common LE/T dosing regimen was one drop QID. Mean (SD) IOP was 15.2 (4.4) mm Hg at baseline and 15.7 (4.4) mm Hg at the first follow-up visit (p = 0.2467). No AEs were recorded, and there were no significant changes in mean VA. Where recorded, most patients (83%) were noted as having their condition resolved/resolving at the first or second follow-up visit. LE/T appears to have a high level of safety when used for the management of various ocular surface inflammatory conditions encountered in optometric practice.

Whole-genome sequencing unravels novel genetic determinants and regulatory pathways associated with triamcinolone acetonide-induced ocular hypertension.

Glucocorticosteroids commonly used to treat certain ocular inflammatory conditions cause an unwarranted elevation in intraocular pressure (IOP) leading to steroid-induced ocular hypertension (OHT). This study aims to identify novel genetic variants in the Indian population associated with steroid responsiveness, specifically to that of intravitreal Triamcinolone acetonide (TA) injections, which leads to OHT in 27% of the TA-treated Indian subjects. Genetic determinants and pathways regulating TA-OHT progression were investigated by applying whole-genome sequencing (WGS) on DNA extracted from 53 blood samples that included TA responders and non-responders. Sequencing analysis yielded 45 intronic and 49 exonic variants to be associated with TA-OHT, which are known to play a vital role in eye, heart, brain, and bone deformities. Of these, the most significant genetic variant associated with TA-OHT was further considered for molecular dynamics (MD) simulation studies. Variants in the CRPPA, PLOD1, ARHGAP1, TIMELESS and TNFSF4 genes were found to be directly implicating TA-OHT. Furthermore, these genes were enriched in pathways associated with cardiomyopathy, focal adhesion, extracellular matrix, and actin cytoskeleton reorganization. MD simulation studies revealed that the top significant variant (rs141625803) in the CRPPA gene possesses a high pathogenic and structurally destabilizing effect. Thus, novel genetic variants that could be significantly associated with the TA-OHT progression were identified in this study. Validation of these targets in a larger cohort of patients along with their functional analysis would inform on the disease, thereby adding to the existing knowledge on the pathophysiology of TA-OHT.

Inflammatory ocular comorbidities in alopecia areata: A retrospective cohort study of a single academic center

To the Editor: Chronic inflammatory dermatological diseases, such as atopic dermatitis and psoriasis, have been associated with inflammatory ocular disorders. Certain ocular conditions, such as uveitis, have also been observed in alopecia areata (AA) in limited studies.1 To identify a possible association between AA and inflammatory ocular conditions, we examined the prevalence of ocular conditions in patients with AA at a tertiary care medical center over the past decade.

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Scleritis.

IntroductionThis article points out the design, methods, development and deployment of the international registry promoted by the AutoInflammatory Disease Alliance (AIDA) Network with the aim to define and assess paediatric and adult patients with immune-mediated scleritis.MethodsThis registry collects both retrospective and prospective real-world data from patients with non-infectious scleritis through the Research Electronic Data Capture (REDCap) tool and aims to promote knowledge and real-life evidence from patients enrolled worldwide; the registry also allows the collection of standardised data, ensuring the highest levels of security and anonymity of patients’ data and flexibility to change according to scientific acquisitions over time. The communication with other similar registries has been also ensured in order to pursue the sustainability of the project with respect to the adaptation of collected data to the most diverse research projects.ResultsSince the launch of the registry, 99 centres have been involved from 20 countries and four continents. Forty-eight of the centres have already obtained a formal approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers); the platform collects baseline and follow-up data using 3683 fields organised into 13 instruments, including patient’s demographics, history, symptoms, trigger or risk factors, therapies and healthcare utilization.ConclusionsThe development of the AIDA International Registry for patients with non-infectious scleritis will allow solid research on this rare condition. Real-world evidence resulting from standardised real-life data will lead to the optimisation of routine clinical and therapeutic management, which are currently limited by the rarity of this ocular inflammatory condition.