To define associations between serologies, specifically Sjögren syndrome-related antigen A (SSA) antibody and immunoglobulin (Ig) levels, on ocular profiles in patients enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) cohort. A retrospective cohort study. Individuals from the SICCA cohort (n = 3514). A retrospective analysis to examine relationships between dry eye (DE) symptoms and signs and serologic status, including SSA (SSA+ Sjögren disease [SjD], SSA- SjD, non-SjD) and Ig (G, A, M) levels (low, normal, and high). Univariate analyses using analysis of variance and chi-square tests examined differences in ocular profiles by serologies. Multivariable analyses were then performed to account for potential confounding variables, including other serological measures. The mean age of the SICCA cohort was 53 ± 13 years, with the majority identifying as female (91%, n = 3185) and White (54%, n = 1894). The presence of SSA impacted ocular profiles, with the SSA+ SjD group reporting less severe symptoms compared with the SSA- SjD and non-SjD groups (spontaneous pain: 2.61 ± 2.83 vs. 3.39 ± 3.01 vs. 3.52 ± 3.09, P < 0.001), but more frequently having ocular signs (low tear production: 57% vs. 52% vs. 28%, P < 0.001; ocular surface staining [OSS]: 83% vs. 69% vs. 35%, P < 0.001). Immunoglobulin levels showed a similar pattern, with the high IgG level group reporting less severe ocular symptoms in the SjD (spontaneous pain: 2.41 ± 2.82 vs. 3.10 ± 2.91 vs. 3.40 ± 2.96; P < 0.001 and P < 0.05) and non-SjD (spontaneous pain: 2.09 ± 2.35 vs. 3.58 ± 3.11 vs. 3.85 ± 3.11; P < 0.001) groups but more severe signs (SjD group: low tear production: 60% vs. 53% vs. 49%; OSS: 88% vs. 72% vs. 70%; P < 0.001) compared with the normal and low-level groups. A similar pattern was noted for IgA levels. Most associations remained significant when considered concomitantly. Ocular manifestations of DE are influenced by serological factors. Specifically, SSA+ and high IgG and IgA status align with a disease picture of clinical signs of DE disease out of proportion to pain symptoms, while SSA- and low and normal IgG and IgA status align with a DE disease picture of symptoms that outweigh signs. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background/Objectives: Post-coronavirus syndrome (long-COVID) refers to a multi-systemic range of symptoms that follows acute SARS-CoV-3 infection. Long-COVID has been linked with autonomic neuropathy as well as dry-eye disease (DED), an umbrella term that includes a variety of ocular symptoms and signs. Despite these associations, little is known about the co-occurrence of DED and dysautonomia symptoms in individuals with long-COVID. This study aims to examine relationships between dysautonomia and ocular symptoms in a long-COVID patient population. Methods: Cross-sectional study of 162 veterans with long-COVID. The Composite Autonomic Symptom Score-31 (COMPASS-31) assessed dysautonomia symptoms, and the NASA lean test and heart-rate variability metrics captured dysautonomia signs. Dry-eye disease (DED) symptoms were measured with the 5-Item Dry-Eye Questionnaire (DEQ5) and the Ocular Surface Disease Index (OSDI), while ocular pain intensity and neuropathic pain descriptors were evaluated using a Numerical Rating Scale (NRS) and select questions from the Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), respectively. Results: Most participants (78%) reported DED symptoms (DEQ5 ≥ 6). Nearly all COMPASS-31 domains were associated with DED symptoms, with the strongest correlation observed between the OSDI and pupillomotor scores (r = 0.67, p < 0.001). Among the autonomic signs, the strongest associations were observed between the change in systolic and diastolic blood pressure from baseline to 8 min and ocular pain triggered by temperature (r = −0.44 and r = −0.48, respectively, p < 0.01 for both). On linear regression analyses, pupillomotor and secretomotor symptoms remained positively associated with DED symptoms, while autonomic signs were most closely related to ocular pain metrics, with fluctuating blood pressure changes during orthostasis relating to neuropathic symptoms. Conclusions: DED symptoms, including ocular pain intensity, relate to autonomic symptoms in a long-COVID cohort. While associations with autonomic signs were less consistent, these data suggest that subtle autonomic variability relates to ocular pain in the long-COVID setting.

Objective: The study aimed to identify symptom‐based predictors of dry eye disease (DED) signs in the Sjögren's International Collaborative Clinical Alliance (SICCA) cohort. Methods: We performed a retrospective analysis examining 16 ocular symptoms (most graded 0–4) and artificial tear (AT) use (graded 0–3) as predictors of DED signs (abnormal ocular surface staining [OSS] and Schirmer's test [ST], graded yes/no). Symptoms included descriptors of spontaneous and evoked pain, visual complaints, and other metrics (eg, redness). Logistic regressions were used for univariable and multivariable analyses, with OSS and ST as outcome variables. Hierarchical analyses were performed to identify symptom‐based clusters. Results: The mean age of the population (n = 3,514) was 53 ± 13 years; 91% were female, 54% were White, and 44% met 2016 criteria for Sjögren disease. On multivariable analysis, OSS was positively related to AT use (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.36–1.67), eye redness (OR 1.17, 95% CI 1.08–1.26), and blurred vision (OR 1.11, 95% CI 1.02–1.20). Similarly, eyes that felt dry, AT use, and blurred vision were positively related to ST. Cluster analysis revealed three groups with varied symptom burden (low, mild‐moderate, and high). The mild‐moderate cluster had higher frequencies of abnormal ocular signs and positive serologic test results (anti‐SSA/Ro antibody, elevated IgG level) compared to the high symptom burden cluster. Conclusion: AT use and blurred vision were stronger indicators of ocular surface and tear film abnormalities than pain symptoms, and their presence merits an ophthalmology referral. Symptom‐based clustering revealed varied symptom burden groups, likely driven by underlying neurotrophic and neuropathic mechanisms, highlighting heterogeneity within sicca presentations and the need to develop phenotype‐based targeted therapies. image