Paediatric non-infectious granulomatous uveitis: a retrospective cohort study.

INTRODUCTION: Paediatric granulomatous uveitis (PGU) is rare. In addition, lack of awareness often leads to delayed diagnosis and poor visual outcome. Identifying the underlying cause and deciding how best to treat each patient is challenging. OBJECTIVES: To evaluate the demographics, aetiologies, complications, treatments, and visual prognosis of paediatric non-infectious granulomatous uveitis. METHODS: Retrospective chart review of non-infectious PGU occurring in children before the age of 16 years recruited from the Paediatric Rheumatology Unit, Bicêtre Hospital, France, from 2001 to 2023. RESULTS: We included 50 patients with 90 affected eyes: 29 with idiopathic uveitis, 15 with sarcoidosis, 5 with juvenile idiopathic arthritis, and one with Vogt-Koyanagi-Harada disease. Median age at diagnosis was 9.8 years (range 7.2-12.5). The sex-ratio M/F was 0.52. The most common features of PGU were: panuveitis (56%), bilateral (84%), and chronic (84%). Sarcoidosis was the most frequent diagnosis after idiopathic disease, particularly in the presence of lymphopenia and hypergammaglobulinemia. Uveomeningitis was present in 12% of cases. Upon diagnosis, ocular complications were present in 68 of 90 eyes (76%) particularly in cases of panuveitis. The most commonly used treatments were systemic corticosteroids (72%) and methotrexate (80%). Twenty-three percent of eyes were in remission at last follow-up, 68% were inactive and 4% remained active. The median duration of follow-up was 5.8 years. CONCLUSION: We report the largest cohort of PGU. PGU were mostly idiopathic and had a high rate of complications. Sarcoid and idiopathic panuveitis are serious illnesses in which disease-modifying therapy should be initiated at diagnosis to improve management.

Efficacy and Safety of Amenamevir, a Helicase-Primase Inhibitor for the Treatment of Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis.

PURPOSE: The purpose of this study was to describe the efficacy and tolerance of amenamevir (AMNV), an inhibitor of the viral helicase-primase, for the treatment of recalcitrant herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) herpes simplex virus 1 strains. METHODS: In this retrospective case series, 6 consecutive patients with HSK caused by an ACVR herpes simplex virus 1 strain with a failure of conventional antiviral therapy were included after having been treated with AMNV (there was no control group of comparable patients for whom previous treatment would have been continued despite its inefficacy). Medical files were assessed for clinical data including reason(s) for AMNV introduction (frequent recurrences despite appropriate preventive antiviral treatment and/or clinical resistance to suppressive antiviral treatment of an ongoing clinical relapse), genotypical resistance to herpes simplex virus 1 documentation, immune status, clinical types and number of HSK episodes before and during AMNV treatment, adverse effects observed during AMNV treatment, and best corrected visual acuity. RESULTS: Of 6 patients, 4 (66%) did not experience a single recurrence during AMNV therapy while 2 others had recurrences (1 over 24 months of treatment and 2 over 23 months, ie two-fold less frequently than with conventional preventive treatment). On the overall history of these 6 patients, AMNV appeared to be associated with a reduction in HSK recurrences, with a mean of only 0.02 ± 0.04 episodes/month during follow-up under AMNV as compared to 0.14 ± 0.04 episodes/month in the year preceding AMNV introduction (P = 0.03). Improvement in vision acuity was also observed (mean best corrected visual acuity 0.17 ± 0.12 logarithm of the minimum angle of resolution at the end of follow-up vs. 0.30 ± 0.35 before AMNV onset), albeit nonsignificant probably due to the limited number of patients (P = 0.38). Neither clinical nor biological adverse effects were observed while under AMNV during the follow-up (16.5 ± 5.8 months). CONCLUSIONS: Although there was no control group, AMNV may be a valuable option to reduce ACVR HSK recurrences.

Immune Checkpoint Inhibitor-induced Sicca Syndrome.

The development of sicca in patients treated with immune checkpoint inhibitors (ICIs) is undoubtedly an underestimated complication, but one whose functional consequences and impact on quality of life are significant for patients. This update aims to review the frequency of this complication and different clinical pictures. The authors also propose a diagnostic and therapeutic approach to guide clinicians in daily practice.

The PRAMOS Study: PRostaglandin Analogues Monotherapy-Awareness Survey on Ocular Surface Involvement.

INTRODUCTION: Even though the local tolerance of prostaglandin (PG) analogues has improved drastically since the introduction of preservative-free (PF) eye drops, prescription patterns still vary widely among practitioners and between countries and could have an impact on the ocular surface of treated patients and, in consequence, their adherence. The aim of this study is to explore the prescribing patterns of PG analogues monotherapy in France and to evaluate their impact on ocular surface status. METHODS: This was a national multicenter cross-sectional observational study that was conducted by 18 glaucoma experts in France. Patients over 18 years of age and receiving monotherapy with topical PG analogues for the treatment of ocular hypertension and/or glaucoma, with no history of prior glaucoma surgery, were consecutively selected from the glaucoma outpatient clinics of participating physicians and underwent an ocular surface examination. RESULTS: A total of 344 eyes of 344 patients were enrolled between November 2022 and November 2023. Prescribed PG monotherapy was PF in 271 (78.7%) patients. Clinical history and ocular surface evaluation indicated that 79.4% of the study population (n = 273) presented with at least one symptom or clinical sign of dry eye and that three patients out of four had an unstable tear film. Subgroup analysis comparing preserved and PF PG analogues showed a higher prevalence of conjunctival hyperemia and corneal staining in the preserved group. Multivariate analysis identified conjunctival hyperemia as consistently associated with preservative use (odds ratio = 7.654; p = 0.003 for moderate conjunctival hyperemia). CONCLUSIONS: This study highlights the growing trend toward PF PG analogue prescriptions by specialists in France. However, ocular surface issues remain prevalent, impacting patient adherence and treatment efficacy. Comprehensive ocular surface examinations are crucial in glaucoma management to enhance long-term tolerance, compliance, and overall treatment success.

Dry Eye Disease in the Middle East and Northern Africa: A Position Paper on the Current State and Unmet Needs.

In the Middle East and Northern Africa (MENA), dry eye disease (DED) is often misdiagnosed or overlooked. This review summarizes a series of conversations with ophthalmologists in the region around a variety of climatic, lifestyle, and iatrogenic factors that contribute to specific features of DED in the MENA region. These considerations are further classified by patient lifestyle and surgical choices. All statements are based on discussions and formal voting to achieve consensus over three meetings. Overall, a deeper understanding of the disease characteristics of DED specific to MENA can better guide local eyecare practitioners on appropriate management and follow-up care. Additionally, population-based studies and patient and physician education on ocular surface diseases, together with the use of culturally appropriate and language-specific questionnaires can help ease the public health burden of DED in this region.

Identification of Structures Labeled by Indocyanine Green in the Rat Choroid and Retina Can Guide Interpretation of Indocyanine Green Angiography.

Purpose: Indocyanine green (ICG) is an albumin and lipoprotein binding dye absorbing in the far red used in angiography to visualize choroidal vessels (ICG angiography [ICGA]). To guide interpretation, ICG transport in the choroid, RPE, and retina of rats was studied. Methods: Two conditions were used: RPE/choroid organoculture, incubated for 45 minutes in DMEM medium, 1% fetal bovine serum containing 0.25 mg/mL ICG and RPE/choroid and neural retina flat-mounts at 1 and 6 hours after intravenous ICG injection. Early and late sequences of ICGA were recorded until 6 hours. Ultra-deep red confocal microscope was used to localize ICG in flat-mounts and immunohistochemistry was performed for caveolin-1, tryptase (mast cell marker), and tubulin ß3 (a nerve marker). Results: In the organoculture, ICG penetrated homogeneously in the cytoplasm and stained the membranes of the RPE. At 1 hour after intravenous injection, ICG appeared in fine granules in RPE, partly labeled with caveolin-1 and decreasing at 6 hours. At 1 hour and 6 hours, ICG was found in the retinal vessels, faintly in the inner retina, and in the photoreceptor outer segments at 6 hours. In the choroid, ICG colocalized with mast cells, immunostained with tryptase, and accumulated along the large tubulin ß3-labeled nerve bundles. The hypothesis was raised on the interpretation of late ICGA infrared photography in case of transthyretin amyloidosis with neuropathy. Conclusions: Beside being a vascular dye, ICG is transported from the vessels to the RPE toward the outer retina. It stains mast cells and large choroidal nerves. These observations could help the analysis of ICGA images.

Ocular surface toxicities associated with modern anticancer therapies.

Cancer treatments have recently shifted from broad-spectrum cytotoxic therapies to more focused treatments, maximizing anticancerous activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) encompass a wide range of innovative molecules that include immune checkpoint inhibitors and other targeted anticancer therapies, comprising antibody drug conjugates and inhibitors of signal transduction. Some MATs are associated with ocular surface adverse events that can cause severe discomfort and even lead to loss of vision. While these complications remain rare, they are probably underreported. It is likely that both oncologists and ophthalmologists will come across MATs-associated ocular surface-adverse events in their practices, owing to the increasing number of patients being treated with MATs. Rapid identification of ocular surface-adverse events is crucial, as early intervention can manage these conditions to avoid vision loss and reduce negative impacts on quality of life. We discuss characteristics of ocular surface pathologies attributed to MATs, describe the suspected underlying pathophysiological mechanisms, and outline the main lines of treatment.

Diagnostic performance of real-time quantitative PCR in tear samples in various subtypes of herpes simplex keratitis.

Diagnosis of herpes simplex keratitis (HSK) is mostly based on clinical findings, yet biological confirmation supports management of challenging cases. This study evaluated the place of real-time quantitative PCR (RT-qPCR) on tear samplings in the management of HSK. Clinical records of patients who underwent tear sampling tested by RT-qPCR for herpes simplex virus type 1 for an acute episode of corneal inflammation or defect between January 2013 and December 2021 were retrospectively reviewed, and results were compared to clinical diagnosis (i.e., HSK or not) based on biomicroscopic findings and medical history. Of 465 tested tear samples from 364 patients, a clinical diagnosis of active (ongoing) HSK was recorded in 240 cases, among which 76 were RT-qPCR positive (global sensitivity of 31.6%, specificity of 99.5%). Sensitivity of RT-qPCR was higher in epithelial (97.4%) and stromal keratitis with ulceration (48.7%), compared to other types of HSK (23.5% in keratouveitis, 13.6% in endotheliitis, 11.1% in postherpetic neurotrophic keratopathy, and 8.1% in stromal keratitis without ulceration). The highest viral loads were detected from epithelial and stromal keratitis with ulceration, while in HSK with no epithelial involvement, the viral load detected was 196-fold lower, on average. The proportion of clinically characterized HSK patients with negative tear samples was higher in patients receiving antiviral treatment (P < 0.0001). RT-qPCR, performed on tear samples, can help in confirming diagnosis in case of presumed HSK, including clinical forms with no obvious epithelial involvement. The sensitivity of tear sampling is much higher whenever epithelial keratitis is present.

Ocular Manifestations of Flavivirus Infections.

Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections and epidemics on a global scale. They represent a major cause of systemic morbidity and death and are expanding worldwide. Among this group, dengue fever, the West Nile virus, yellow fever, Japanese Encephalitis, and, recently, the Zika virus have been linked to a spectrum of ocular manifestations. These manifestations encompass subconjunctival hemorrhages and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatments of flavivirus infections are currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for the yellow fever virus, dengue virus, and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic manifestations of the foremost flavivirus-associated human diseases.

Ocular involvement in pediatric Behçet's disease: is it different than in adults? (a short case series and mini review).

BACKGROUND: Pediatric Behçet's disease (PBD) is rarer than BD and can be a challenging diagnosis as clinical picture may be incomplete. As in adult patients, sight-threatening ocular manifestations may lead to diagnosis. In this study, we aimed to report a series of cases of PBD with ocular manifestations and provide a review of the literature. METHODS: Retrospective case series of PBD patients with ocular manifestations. Demographic, ophthalmological and systemic data at presentation and during follow-up were collected and analyzed. RESULTS: Four patients, aged 13.0 ± 2.9 years (9-16) were included. Posterior uveitis with retinal vasculitis, papillitis and macular edema was present in all patients, with associated anterior uveitis in 2 cases. Other features included occlusive vasculitis (2/4) and necrotizing retinitis (2/4). All patients were improved by systemic treatments except one patient with severe bilateral optic neuropathy. Ocular manifestations were the presenting symptoms in 3/4 cases. CONCLUSION: Ocular manifestations and systemic associations of PBD are comparable to those encountered in adult patients. The lack of complains in pediatric patients may lead to a longer diagnosis delay, especially in unilateral uveitis. Aggressive and long-term treatment is mandatory to prevent vision loss and recurrences.

Comparison between primary Sjögren's disease patients with high or low level of dryness.

OBJECTIVES: To describe primary Sjögren's disease (SjD) patients presenting no or low level of dryness and to compare them with SjD patients with oral or ocular dryness features. METHODS: All patients diagnosed with SjD according to AECG or ACR/EULAR criteria in our tertiary reference centre were included. Patients with high or low subjective symptoms or objective signs of dryness were compared. RESULTS: Overall, 509 patients were included for the comparison of patients with high (n=456) or low (n=53) level of subjective dryness and 472 for the comparison of patients with (n=359) or without (n=113) high objective dryness. Compared with patients with subjective dryness, patients without high subjective dryness were significantly younger (median 49 (39-62) years vs 58 (47-67) years, p<0.01), diagnosed earlier (median time from first symptoms to diagnosis 2 (0.5-4.5) years vs 4 (1-9.25), p=0.0056), more frequently anti-SSA positive ((83% vs 64%, p=0.008) and had less focal sialadenitis in minor salivary gland biopsy (69% vs 83%, p=0.02).The patients without high level of objective dryness (n=113) were also younger (51 (41-60) vs 58 (47-67) years, p<0.001) and were more frequently anti-SSA positive (79% vs 63%, p=0.002).In both groups, no difference was observed regarding disease activity. CONCLUSIONS: Among the patients with SjD, those without high subjective or objective dryness features had a younger profile, a faster diagnosis which may result from a more acute onset, were more frequently anti-SSA positive than patients with high dryness features.

Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature.

PURPOSE: To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments. METHODS: Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO). RESULTS: Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 µm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results. CONCLUSIONS: Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.

Mueller polarimetric imaging as a tool for detecting the effect of non-thermal plasma treatment on the skin.

Non-thermal plasma (NTP) is a promising technique studied for several medical applications such as wound healing or tumor reduction. The detection of microstructural variations in the skin is currently performed by histological methods, which are time-consuming and invasive. This study aims to show that full-field Mueller polarimetric imaging is suitable for fast and without-contact detection of skin microstructure modifications induced by plasma treatment. Defrosted pig skin is treated by NTP and analyzed by MPI within 30 minutes. NTP is shown to modify the linear phase retardance and the total depolarization. The tissue modifications are inhomogeneous and present distinct features at the center and the fringes of the plasma-treated area. According to control groups, tissue alterations are primarily caused by the local heating concomitant to plasma-skin interaction.

Comparison between tafamidis and liver transplantation as first-line therapy for hereditary transthyretin amyloidosis.

BACKGROUND: By stabilizing transthyretin, tafamidis delays progression of amyloidosis due to transthyretin variant (ATTRv) and replaced liver transplantation (LT) as the first-line therapy. No study compared these two therapeutic strategies. METHODS: In a monocentric retrospective cohort analysis, patients with ATTRv amyloidosis treated with either tafamidis or LT were compared using a propensity score and a competing risk analysis for three endpoints: all-cause mortality, cardiac worsening (heart failure or cardiovascular death) and neurological worsening (worsening in PolyNeuropathy Disability score). RESULTS: 345 patients treated with tafamidis (n = 129) or LT (n = 216) were analyzed, and 144 patients were matched (72 patients in each group, median age 54 years, 60% carrying the V30M mutation, 81% of stage I, 69% with cardiac involvement, median follow-up: 68 months). Patients treated with tafamidis had longer survival than LT patients (HR: 0.35; p = .032). Conversely, they also presented a 3.0-fold higher risk of cardiac worsening and a 7.1-fold higher risk of neurological worsening (p = .0071 and p < .0001 respectively). CONCLUSIONS: ATTRv amyloidosis patients treated with tafamidis would present a better survival but also a faster deterioration of their cardiac and neurological statuses as compared with LT. Further studies are needed to clarify the therapeutic strategy in ATTRv amyloidosis.

Hijacking the Peptidoglycan Recycling Pathway of Escherichia coli to Produce Muropeptides.

Soluble fragments of peptidoglycan called muropeptides are released from the cell wall of bacteria as part of their metabolism or as a result of biological stresses. These compounds trigger immune responses in mammals and plants. In bacteria, they play a major role in the induction of antibiotic resistance. The development of efficient methods to produce muropeptides is, therefore, desirable both to address their mechanism of action and to design new antibacterial and immunostimulant agents. Herein, we engineered the peptidoglycan recycling pathway of Escherichia coli to produce N-acetyl-ß-D-glucosaminyl-(1→4)-1,6-anhydro-N-acetyl-ß-D-muramic acid (GlcNAc-anhMurNAc), a common precursor of Gram-negative and Gram-positive muropeptides. Inactivation of the hexosaminidase nagZ gene allowed the efficient production of this key disaccharide, providing access to Gram-positive muropeptides through subsequent chemical peptide conjugation. E. coli strains deficient in both NagZ hexosaminidase and amidase activities further enabled the in vivo production of Gram-negative muropeptides containing meso-diaminopimelic acid, a rarely available amino acid.

IS CATARACT SURGERY SAFE IN PATIENTS WITH STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS?

PURPOSE: To assess the retinal modifications after cataract surgery in a patient presenting with stellate nonhereditary idiopathic foveomacular retinoschisis. METHODS: Retrospective analysis of the evolution of retinal status in a 64-year-old patient with unilateral stellate nonhereditary idiopathic foveomacular retinoschisis who underwent cataract surgery in the affected eye. RESULTS: Visual acuity improved after surgery, reaching back the level described by the patient before the cataract onset, whereas fundus retinographies and optical coherence tomographies were stable at one month after surgery, compared with the preoperative images. DISCUSSION: This first case-report of the evolution of stellate nonhereditary idiopathic foveomacular retinoschisis after cataract surgery suggests that this retinal condition is not modified by the surgical procedure, which however needs to confirmed by larger cohorts.

Herpes simplex virus, varicella-zoster virus and cytomegalovirus keratitis: Facts for the clinician.

Keratitis due to Herpes simplex virus (HSK), Varicella-Zoster virus (VZK) and Cytomegalovirus remains a frequent source of concern for many ophthalmologists. They are a frequent cause of emergency consultations at eye care centers and carry the risk of permanent loss of visual acuity or visual quality and/or chronic neurotrophic keratitis, resulting in a significant decrease in the quality of life. HSK and VZK can affect the corneal epithelium, stroma, or endothelium or a combination of layers. In contrast, most cases of CMV keratitis present as isolated endothelitis (CMVE), a clinical entity that has been described within the last 2 decades. These three types of viral keratitis are characterized by a high frequency of recurrences and each new episode increases the risk of sequelae. Hence, ophthalmologists must adapt the treatment to the clinical presentation of each recurrent episode in order to mitigate the immediate consequences of viral replication and the immune response on corneal transparency. In patients with frequent recurrences, preventive long-term antiviral treatment is strongly recommended. However, in some rare cases, continuous exposure to antivirals may promote the emergence of resistant viral strains, which can be difficult to manage. In the future, the introduction of new antiviral drugs, with differing modes of action compared to current medical therapy, could be an alternative until a truly effective preventive solution, such as a vaccine, is available.

Ocular Inflammation Induced by Immune Checkpoint Inhibitors.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi-Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs.

Clinical course and treatment of archipelago keratitis: a Herpesviridae keratitis subtype.

PURPOSE: Archipelago keratitis (ApK) is a subtype of Herpesviridae stromal keratitis that consists of subepithelial nummular inflammatory infiltrates arranged in a radial centripetal pattern. This rare and poorly described form is not often recognised early. We report the first large series of ApK, with an analysis of clinical settings at presentation, evolution of the disease with time and a description of factors associated with recurrence. METHODS: The clinical records of 82 patients (83 eyes) with a diagnosis of ApK between 2011 and 2021 in two centres were reviewed. RESULTS: The median age of the 82 patients at referral was 37±28 years. ApK was unilateral in all but one case. A total of 76% of patients had at least one second diagnostic criteria suggesting a herpetic aetiology. Overall, 44 (53%) eyes exhibited least one recurrence after a median of 12 months. Recurrence was frequently associated with neovascularisation (HR 2.1, 95% CI 1.1 to 3.9; p=0.02) and tapering corticosteroids (HR 3.5, 95% CI 1.8 to 7.1; p<0.01) or valaciclovir use (HR=2.3, 95% CI 1.2 to 4.6; p=0.01). Antiviral treatment was used in all patients, whereas local anti-inflammatory drugs such as corticosteroids and/or ciclosporin were used in 73 (88%) cases. CONCLUSION: ApK is a Herpesviridae stromal keratitis that is typically unilateral in presentation and features a high risk of recurrence. Combined treatment with antiviral and anti-inflammatory drugs are usually required over the long term. Topical ciclosporin can be useful as a corticosteroid-sparing treatment.

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome.

OBJECTIVES: To assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients. METHODS: In this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected. RESULTS: A total of 253 patients (245 females) with confirmed pSS, aged 56.6±13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio-OR-=1.25 per OSS unit increase; confidence interval-CI-95%=1.05-1.49; P=0.01; OR=1.31 per OSS unit increase; CI95%=1.09-1.58, P=0.002, and OR=1.34 per OSS unit increase; CI95%=1.12-1.59; P=0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR=2.03; CI95%=1.03-4.00; P<0.05 and OR=2.52, CI95%=1.31-4.90; P<0.01, respectively). CONCLUSION: Association between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.