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Increased expression of B cell activating factor (BAFF or B lymphocyte stimulator) may explain the B cell activation characteristic of primary Sjögren's syndrome (pSS). To evaluate the efficacy and safety of belimumab, targeting BAFF, in patients with pSS. Patients were included in this bi-centric prospective 1-year open-label trial if they fulfilled American European Consensus group criteria, were anti-Sjögren's syndrome A-positive and had current systemic complications or salivary gland enlargement, or early disease (<5 years), or biomarkers of B cell activation. They received belimumab, 10 mg/kg, at weeks 0, 2 and 4 and then every 4 weeks to week 24. The primary end-point, assessed at week 28, was improvement in two of five items: reduction in ≥30% in dryness score on a visual analogue scale (VAS), ≥30% in fatigue VAS score, ≥30% in VAS pain score, ≥30% in systemic activity VAS assessed by the physician and/or >25% improvement in any B cell activation biomarker values. Among 30 patients included, the primary end-point was achieved in 18 (60%). The mean (SD) European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index decreased from 8.8 (7.4) to 6.3 (6.6) (p=0.0015) and EULAR) Sjögren's Syndrome Patient Reported Index from 6.4 (1.1) to 5.6 (2.0) (p=0.0174). The mean dryness, fatigue and pain VAS varied from 7.8 (1.8) to 6.2 (2.9) (p=0.0021), 6.9 (1.8) to 6.0 (2.2) (p=0.0606) and 4.6 (2.6) to 4.7 (2.4) (p=0.89), respectively. Salivary flow and Schirmer's test did not change. These encouraging results justify future randomised controlled trials of belimumab in a selected target population of pSS patients most likely to benefit from treatment.

We describe a multiannual outbreak of keratoconjunctivitis caused by the microsporidium Vittaforma corneae in the Sea of Galilee, Israel. Patients had multifocal punctate corneal infiltrates and reduced visual acuity, confirmed by locally-developed pathogen-specific real-time PCR. Topical chlorhexidine, rather than traditional antimicrobial drugs, proved an effective and safe primary treatment.

Background Keratoconjunctivitis sicca or dry eye disease (DED) is a multifactorial disorder underpinned by a complex inflammatory cycle. Introduction of topical cyclosporine has been a significant advance in the management of DED. In recent years advancements in formulation technology have led to development of micellar nano-particulate (MNP) cyclosporine formulations that promise better penetration into ocular target tissues and potential for reduced ocular surface irritation. Methods We compared two dosing regimes of a proprietary MNP cyclosporine emulsion with the widely marketed topical cyclosporine formulation Restasis™ in a multicenter parallel-group randomised trial in patients with DED. Patients were randomised to one of 3 treatment groups with 90 patients eligible for the per protocol analysis: 30 in the higher dose test arm A; 32 in the lower dose test arm B; and 28 in the Restasis™ control arm C. All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group at 12 weeks, using the Student’s t test. Wilcoxon’s rank sum test was used to test individual symptom scores and clinician’s global evaluation of treatment grades. Results Corneal fluorescein staining score, the primary efficacy endpoint, decreased by 6.8 ± 4.0, 5.7 ± 3.9, and 4.6 ± 3.6 points in the 3 groups respectively, indicating superior efficacy in test arm A in comparison to control arm C (p = 0.0026). Schirmer’s tear test, conjunctival lissamine staining score, ocular surface disease index, and individual dry eye symptom scores also favoured higher dose MNP cyclosporine over Restasis™. The study failed to differentiate the treatment arms in terms of clinician’s global evaluation of treatment, use of tear substitutes, best corrected visual acuity or safety and toleration. Conclusion The results indicate that the dose of 1 drop of a 0.05% w/v ophthalmic emulsion of MNP cyclosporine administered topically twice daily yields better outcomes at 12 weeks than the lower dose tested in the study, and is more efficacious than an equivalent dose of Restasis™, the active control used in the study. Trial registration This trial was registered in the Clinical Trials Registry of India on 29/03/2019, and was assigned registration number CTRI/2019/03/018319.

Background Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, many studies have reported the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the conjunctival sac of patients infected with this virus, with several patients displaying symptoms of viral conjunctivitis. However, to our best knowledge, there is no in-depth report on the course of patients with COVID-19 complicated by relapsing viral conjunctivitis or keratoconjunctivitis. Case presentation A 53-year-old man confirmed with COVID-19 developed symptoms of viral conjunctivitis in the left eye approximately 10 days after the onset of COVID-19. The results of a nucleic acid test were positive for SARS-CoV-2 in the conjunctival sac of the left eye. The symptoms were relieved 6 days after treatment. However, the patient was subsequently diagnosed with viral keratoconjunctivitis in both eyes 5 days after the symptoms in the left eye were satisfactorily relieved. The disease progressed rapidly, with spot staining observed at the periphery of the corneal epithelium. Although SARS-CoV-2 could not be detected in conjunctival secretions, the levels of inflammatory factors, such as interleukin-6, were increased in both eyes. Both eyes were treated with glucocorticoids, and symptoms were controlled within 5 days. There was no recurrence. Conclusions In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported.

Adenovirus type 37 (Ad37) causes epidemic keratoconjunctivitis, a highly contagious disease for which there is no specific antiviral therapy. The receptor for Ad37 infection was previously unidentified, but known to contain sialic acid. Nilsson et al . report here that Ad37 binds to the GD1a glycan motif of the GD1a ganglioside. This finding may facilitate the development of antiviral agents targeting Ad37-associated disease. Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC) 1 , 2 , a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid–containing cell surface molecules 3 , 4 . By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid–binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob–GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid–containing antiviral drugs for topical treatment of EKC.

Among patients with dry eye disease, those who were randomly assigned to receive oral supplements containing fish-derived n−3 eicosapentaenoic and docosahexaenoic acids did not have significantly better outcomes at 1 year than those who received placebo.

PurposeEpidemic keratoconjunctivitis (EKC) is one of the most severe ocular viral infections. The aim of this interruptive time series study was to quantitatively evaluate the effectiveness of a hygienic EKC outbreak management concept developed in our ophthalmological department.MethodsAll patients with suspected EKC in the period from August to November 2018 were included in the study. Data were retrospectively collected from the patient’s medical documents and records. The disease was diagnosed clinically and confirmed by virus detection through polymerase chain reaction (PCR) from conjunctival swabs. With the beginning of the epidemic, an outbreak management plan was implemented to reduce the nosocomial spread.ResultsThe outbreak lasted 77 days (20th August 2018 to 4th November 2018) and affected a total of 120 patients. This corresponds to a mean of 1.5 patients per outbreak day. The median age was 58 [1–92] years. Of all patients, 61 (50.8%) were female. Conjunctival swabs were collected in 100/120 (83.3%) cases, the adenovirus being detected in all positive smears (63/63, 100%). The implementation of our outbreak management plan reduced significantly the number of EKC cases per outbreak day and resulted in a reduction of the basic reproduction number by a factor of 2.2.ConclusionThe detection of EKC together with the immediate implementation of hygienic outbreak measures can significantly reduce the spread of infection. The implementation of a strict outbreak management concept can significantly reduce the number of EKC cases, thus avoiding possible complications and therefore unnecessary health-related costs.

Aims: To evaluate the efficacy of 50% autologous serum drops against conventional treatment in ocular surface disorders refractory to normal treatments in a prospective randomised crossover trial. Method: Patients fulfilling ophthalmological and haematological entry criteria were randomised to either 3 months of autologous serum 50% followed by 3 months of their conventional treatment, or 3 months of conventional treatment, followed by 3 months of autologous serum. Clinical assessments, including Schirmer’s test, rose Bengal, and fluorescein staining, were carried out on entry and at monthly intervals. Impression cytology was performed at entry, 3 and 6 months. Grading was carried out on degrees of squamous metaplasia and goblet cell density. Subjective comfort was recorded daily using the “faces” scale. These categorical scores were converted to linear measurement using Rasch analysis. Statistical analysis was carried out using Wilcoxon’s signed rank test and ANOVA. Results: 16 patients were recruited with 31 eyes studied. The ocular surface diseases chiefly included Sjögren’s syndrome (n = 6) and keratoconjunctivitis sicca (n = 5). Impression cytology available in 25 of 31 eyes showed significant improvement on serum treatment, p<0.02. Rasch weighted faces scores were statistically significantly better with serum, p<0.01. Conclusion: The results of this randomised study provide further evidence of the beneficial effects of autologous serum in severe ocular surface disorders. For most of these patients, autologous serum was superior to conventional treatment for improving ocular surface health and subjective comfort.

A highly contagious infection caused by human adenovirus species D (HAdV-D), epidemic keratoconjunctivitis (EKC) results in corneal subepithelial infiltration (SEI) by leukocytes, the hallmark of the infection. To date, the pathogenesis of corneal SEI formation in EKC is unresolved. HMGB1 (high-mobility group box 1 protein) is an alarmin expressed in response to infection and a marker of sepsis. Earlier studies using a different adenovirus species, HAdV-C, showed retention of HMGB1 in the infected cell nucleus by adenovirus protein VII, enabling immune evasion. Here, using HAdV-D we show cell-specific HMGB1 secretion by infected cells, and provide an HAdV-D specific mechanism for SEI formation in EKC. HMGB1 was secreted only upon infection of human corneal epithelial cells, not from other cell types, and only upon infection by HAdV-D types associated with EKC. Acetylated HMGB1 translocation from the nucleus to the cytoplasm, then to the extracellular milieu, was tightly controlled by CRM1 and LAMP1, respectively. Primary stromal cells when stimulated by rHMGB1 expressed proinflammatory chemokines. In a novel 3D culture system in tune with the architecture of the cornea, HMGB1 released by infected corneal epithelial cells induced leukocytic infiltrates either directly and/or indirectly via stimulated stromal cells, which together explains SEI formation in EKC.

Keratoconjunctivitis sicca (KCS), also commonly known as dry eye disease (DED), is one of the most prevalent and crippling features of Sjögren disease (SD), a chronic systemic autoimmune disorder featuring lymphocytic infiltration and progressive impairment of exocrine glands. KCS affects up to 95% of patients with SD and is often the earliest and most persistent manifestation, significantly compromising visual function, ocular comfort, and overall quality of life. Beyond the ocular surface, KCS mirrors a wider spectrum of immune dysregulation and epithelial damage characteristic of the disease, making it a valuable window into the underlying systemic pathology. The pathophysiology of KCS in SD is complex and multifactorial, involving an interplay between autoimmune-mediated lacrimal gland dysfunction, neuroimmune interactions, ocular surface inflammation, and epithelial instability. Tear film instability and epithelial injury result from the aberrant activation of innate and adaptive immunity, involving T and B lymphocytes, pro-inflammatory cytokines, and type I interferon pathways. Despite the clinical significance of KCS, its diagnosis remains challenging, with frequent discrepancies between subjective symptoms and objective findings. Traditional diagnostic tools often lack sensitivity and specificity, prompting the development of novel imaging techniques, tear film biomarkers, and standardized scoring systems. Concurrently, therapeutic strategies have evolved from palliative approaches to immunomodulatory and regenerative treatments, aiming to restore immune homeostasis and epithelial integrity. This review provides a comprehensive update on the pathogenesis, diagnostic landscape, and emerging treatments of KCS in the context of SD.