Salivary cortisol, α-amylase (sAA), secretory IgA (sIgA), testosterone, and soluble fraction of receptor II of TNFα (sTNFαRII) could serve as objective pain measures, but the normal variability of these potential biomarkers is unknown. Saliva was collected with the passive secretion method from 34, pain-free subjects in two single samples at least 24 hours apart. Biomarker variation and intersession reliability were assessed with the intraclass correlation coefficient (ICC). Also, we calculated the within-subject standard deviation (S_w) and the reproducibility (2.77 × S_w) of intersession measures. Salivary cortisol, sAA, sIgA, testosterone, and sTNFαRII yielded the following ICCs: 0.53, 0.003, 0.88, 0.42 and 0.83, respectively. We found no statistically significant systematic differences between sessions in any biomarker except for testosterone, which showed a decrease on the second day (p<0.001). The reproducibility for salivary cortisol, sAA, sIgA, testosterone, and sTNFαRII were 0.46 ng/ml, 12.88 U/ml, 11.7 μg/ml, 14.54 pg/ml and 18.29 pg/ml, respectively. Cortisol, testosterone and TNFαRII measurement variability showed a positive correlation with the magnitude (p<0.002), but no relationship was found for sAA and sIgA. Salivary sIgA and sTNFαRII show a remarkable good reproducibility and, therefore, could be useful as pain biomarkers. When using the passive secretion method, intersession variations in salivary sIgA of more than 11.7 μg/ml may reflect true biomarker change. In the case of sTNFαRII this will depend of the magnitude. The estimates herein provided should help investigators and clinicians differentiate actual biomarker modification from measurement variability.

Purpose: Laser vision correction is one of the most commonly performed elective surgical procedures in ophthalmology. Generally, discomfort besides pain (photophobia, burning sensation, tearing, and foreign body sensation) after these procedures is not taken into consideration in the clinical practice. The objective is to provide data on these symptoms and their relevance after advanced surface ablation (ASA). Methods: Single-center survey study based on a structured questionnaire relative to the patients’ perceived symptoms after ASA. Inclusion criteria were: ≥18 years old, no ocular disease, with myopia (0.75 to 9 D) or hyperopia (0.25 to 5 D) with or without astigmatism, receiving ASA on at least one eye. All procedures were performed by the same surgeon. A descriptive analysis was performed. Results: Seventy-three consecutive patients (34 men and 39 women) were included in the study. The median (range) of age was 33 (19–64) years. Sixty-nine patients had surgery done on both eyes. Postoperative pain was the most frequent comorbidity (97% [95% confidence interval {CI}: 90–100]) with a median (range) of intensity (verbal numerical rating scale) score of 7 (2–10). Photophobia: 85% (95% CI: 75–92); burning sensation: 62% (95% CI: 50–73); tearing: 59% (95% CI: 47–70); and foreign body sensation: 48% (95% CI: 36–60) were also prevalent postoperative symptoms. Pain during ASA was reported for 44% (95% CI: 32–56) of patients. Conclusion: Comorbidities such as pain, photophobia, burning sensation, tearing, and foreign body sensation are prevalent after ASA procedure. Postoperative pain should be taken into consideration due to its prevalence and intensity. A new and more efficient postoperative analgesic protocol should be established.

Purpose: The objective of this study was to characterize the evolution of ocular pain after advanced surface ablation (ASA) to improve strategies in postoperative pain management. Methods: This was a multicenter, prospective, descriptive, cohort study. The inclusion criteria were healthy individuals ≥18 years old receiving bilateral alcohol-assisted surface ablation with epithelial removal. Pain intensity was evaluated with the visual analog scale (VAS) and the numeric pain rating scale before and after surgery. Comorbidities (photophobia, burning, tearing, and foreign body sensation) and Hospital Anxiety and Depression (HAD) questionnaire were evaluated before and at 6 hours after surgery. Postoperative treatments included cold patch, topical cold antibiotics, topical steroids, and benzodiazepines. Results: Thirty-two consecutive patients having similar profiles of postoperative pain evolution were included. At 0.5 hour after ASA, the pain score by VAS was 37±20 mm, and the maximum pain, 61±31 mm, occurred at 24 hours. Afterward, it decreased progressively until 72 hours after surgery (19±20 mm). Most patients (81%) scored >60 mm, and 44% required rescue medication. Among the comorbidities, all patients had photophobia and 84% had burning sensation. At 6 hours, the HAD score was 5.4±3.9, within the range of values considered as normal. Conclusion: Postoperative acute ocular pain after ASA showed a characteristic evolution over time. Recognition of the pattern could be important for improving the acceptance of ASA and for improving strategies in pain management in the postoperative period.

Purpose: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication. Design: Cross-sectional study. Participants: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects. Methods: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM). Results: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (−2.57 (−1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm²), nerve branching density (2 (2.50) n/mm²), and dendritic cell density (9.1 (8.84) n/mm²) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels. Conclusions: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.

Purpose: Patients with Retinitis Pigmentosa (RP) commonly experience sleep-related issues and are susceptible to stress. Moreover, variatiaons in their vision are often linked to anxiety, stress and drowsiness, indicating that stress and sleep deprivation lead to a decline in vision, and vision improves when both are mitigated. The objective of this study was to investigate the utility of salivary biomarkers as biochemical indicators of anxiety and sleep deprivation in RP patients. Methods: Seventy-eight RP patients and 34 healthy controls were included in this observational study. Anxiety and sleep-quality questionnaires, a complete ophthalmological exam for severity grading and, the collection of salivary samples from participants were assessed for participants. The activity of biomarkers was estimated by ELISA, and statistical analysis was performed to determine associations between the parameters. Associations between underlying psychological factors, grade of disease severity, and biomarkers activity were also examined. Results: Fifty-two (67%) of patients had a severe RP, and 26 (33%) had a mild-moderate grade. Fifty-eight (58,9%) patients reported severe levels of anxiety and 18 (23.,1%) a high level. Forty-six (59%) patients obtained pathological values in sleep-quality questionaries and 43 (55.1%) in sleepiness. Patients with RP exhibited significant differences in testosterone, cortisol, sTNFαRII, sIgA and melatonin as compared to controls and patients with a mild-moderate and advanced stage of disease showed greater differences. In covariate analysis, patients with a severe anxiety level also showed greater differences in mean salivary cortisol, sTNFαRII and melatonin and male patients showed lower IgA levels than female. Conclusions: The present findings suggest that salivary biomarkers could be suitable non-invasive biochemical markers for the objective assessment of sleep deprivation and anxiety in RP patients. Further research is needed to characterize the effects of untreated negative psychological states and sleep deprivation on increased variability of vision and disease progression, if any.

Purpose: To evaluate the evolution of a set of proposed pain biomarkers in the saliva of subjects following Advanced Surface Ablation (ASA), in order to determine their validity as objective pain measures. Methods: A multicenter, prospective, and descriptive study was carried out to assess the variations between biomarkers and perceived pain. The Inclusion criteria were healthy subjects who underwent a bilateral, alcohol-assisted surface ablation with epithelial removal (ASA). Pain intensity before and after surgery was assessed by Visual Analog Scale (VAS) and the Numeric Pain Rating Scale (NPRS). Cortisol, sAA, sIgA, testosterone, and sTNF alpha RII were assayed at four-time points (V0, baseline; V1, pre-surgery; V2, 1 hr post-surgery, and V3, 72 hrs post-surgery). Comorbidities and Hospital Anxiety and Depression (HADS) questionnaires were administrated before and at 6 hrs after the surgery. All patients were treated with cold patches, topical steroids, topical cold antibiotics, and benzodiazepines after ASA surgery. A descriptive analysis of biomarkers and pain intensity evolution and the agreement between biomarkers and pain was performed. Results: Concentration of sIgA and sTNF alpha RII post-surgery was significantly higher at each visit compared to baseline (p-value: 0.053, p-value: < 0.001, respectively). Relations between VAS scale score and putative biomarker variations were not statistically significant except for the sIgA but only at visit 0 (p-value: 0.024). The HADS questionnaire showed anxiety scores between 0 and 7 in all patients before and at 6 hrs after surgery. Conclusion: In this study, sIgA and sTNF alpha RII are the two potential biomarkers that present correlation with the VAS and these salivary substances showed acceptable levels of reproducibility in healthy subjects.