To describe the clinical characteristics of patients suffering from chronic dry eye (DE) and pain after refractive surgery (RS). Cross-sectional, observational, single-visit study. DE-, pain- and psychological-related symptoms were evaluated with specific questionnaires. DE-related tests evaluated tear osmolarity, conjunctival hyperemia, Meibomian gland dysfunction, tear stability and production, and ocular surface staining. Corneal mechanical sensitivity (Cochet-Bonnet) was measured pre/post topical anesthesia, and symptomatic variation post-anesthesia (anesthetic challenge test) was recorded. When pain was present, it was further categorized as neuropathic or nociceptive based on published criteria. We recruited 104 patients (39.5 ± 9.5 years). Most, 85.6%, had corneal RS as opposed to intraocular RS. Migraines, anxiety, depression (p < 0.0001), and central sensitization syndromes (p = 0.0214) were more frequent post-RS than pre-RS. Persistent DE-symptoms, severe in 86.5% patients, developed in a range of 0-204 months post-RS. Dryness and pain were the two most frequent symptoms. The only DE-related tests showing abnormal values were tear osmolarity (315.2 ± 17.1 mOsm/L; normal ≤308) and tear break-up time (4.1 ± 2.5 s; normal >7). Corneal sensitivity was 55.4 ± 7.0 mm, and decreased (p < 0.0001) after topical anesthesia, 6.0 ± 10.4 mm. However, it remained pathologically elevated, ≥10 mm in 61 (58.7%) patients. The normal symptomatic post-anesthesia improvement was absent in 58 (55.7%) patients. Ocular pain was present in 82 (78.8%) patients, and it was categorized as neuropathic in 66 (80.5%) of them, 63.5% of the entire cohort. Chronic ocular pain and its neuropathic subtype were diagnosed in 78.8% and 63.5% respectively of patients seeking consultation for persistent symptomatic DE post-RS.

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.

Chronic neuropathic ocular pain (NOP) can develop alongside chronic dry eye (DE) post-laser-assisted in-situ keratomileusis (LASIK), yet its specific characteristics remain poorly understood. This study aims to compare the clinical characteristics of patients who developed both DE and NOP after LASIK to those with only DE and to asymptomatic LASIK patients, to facilitate the diagnosis of NOP. Prospective, cross-sectional "case-control" comparison study. An 89-subject post-LASIK study comprised 3 groups: 34 patients developing NOP and DE (NOP-DE group), 25 patients developing only DE (DE group), and 30 asymptomatic subjects (control group). Assessments included clinical history and symptom questionnaires (OSDI, mSIDEQ, NRS, WFPRS), anxiety and depression evaluation (HADS), tear film stability (osmolarity and TBUT) and production (Schirmer), and ocular surface integrity. Corneal mechanical and thermal sensitivity thresholds were measured using Belmonte's noncontact esthesiometer, whereas tactile sensitivity threshold was assessed pre-/post-topical anesthesia using the Cochet-Bonnet esthesiometer. In vivo confocal microscopy (IVCM) was used to evaluate the sub-basal nerve plexus characteristics and dendritic cell density in the central cornea. Group comparisons and correlations were conducted. Compared with DE group, patients in the NOP-DE group exhibited significantly more DE symptoms with mSIDEQ (P = .019) higher level of pain with NRS and WFPRS, increased use of ocular lubrication (P = .003), greater frequency of patients with pathological results on anxiety and depression questionnaires (P < .001), and a higher prevalence of central sensitization syndromes (P < .001). Additionally, NOP-DE patients demonstrated higher tactile corneal sensitivity post-topical anesthesia (P = .002). IVCM revealed lower nerve density (P = .049) and higher microneuroma density (P = .008) in the sub-basal nerve plexus of NOP-DE patients compared to DE patients without NOP (P = .008). Most nerve metrics correlated moderately to strongly with clinical parameters. Persistent high corneal tactile sensitivity postanesthesia, reduced nerve density, and increased microneuroma density in the central cornea may serve as diagnostic indicators for confirming NOP in patients experiencing chronic DE post-LASIK. These findings underscore the potential utility of incorporating these measures into clinical assessments to improve diagnostic accuracy and guide management strategies in this patient population.

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.

Background/Objectives: The purpose of this study was to clinically characterize the lacrimal functional unit (LFU) of patients with chronic ocular pain associated with dry eye disease (DED). Methods: Ninety-three participants were included in this cross-sectional study: 28 patients with chronic ocular pain associated with DED (pain-DED), 35 patients with DED but no pain (no pain-DED), and 30 subjects without DED or ocular pain (controls). The following examinations were performed: symptom questionnaires, visual function assessment, tear meniscus, ocular surface evaluation, meibography, corneal sensitivity, Schirmer test, and in vivo corneal confocal microscopy. Results: Both DED groups presented increased DED-related symptoms (p < 0.001), corneal staining (p < 0.001), Meibomian gland loss (p < 0.010), and dendritic cell density (p < 0.001) compared with controls. Comparing both DED groups, the pain-DED group showed higher DED-related symptoms (p < 0.002) and increased microneuroma density (p < 0.001). Additionally, significant positive correlations were observed between symptom questionnaires and corneal staining (vs. OSDI: r = 0.514, p < 0.001; vs. m-SIDEQ: r = 0.504, p < 0.001; vs. NRS: r = 0.361, p < 0.001; vs. WBFPRS: r = 0.317, p = 0.002), dendritic cell density (vs. OSDI: r = 0.429, p < 0.001; vs. m-SIDEQ: r = 0.440, p < 0.001), and microneuroma density (vs. NRS: r = 0.405, p < 0.001; vs. WBFPRS: r = 0.416, p < 0.001). Conclusions: Differences in the LFU, especially in the morphology of sub-basal corneal nerves, are related to the presence of DED and chronic ocular pain and, along with ocular clinical questionnaires, can help phenotype these patients.

An automated tool for corneal nerve fiber tortuosity quantification from in vivo confocal microscopy (IVCM) is described and evaluated. The method is a multi-stage process based on the splitting of the corneal nerve fibers into individual segments, whose endpoints are an extreme or intersection of white pixels on a binarized image. Individual segment tortuosity is quantified in terms of the arc-chord ratio. Forty-three IVCM images from 43 laser-assisted in situ keratomileusis (LASIK) surgery patients were used for evaluation. Images from symptomatic dry eye disease (DED) post-LASIK patients, with ($n=16$) and without ($n=7$) ocular pain, and non-DED post-LASIK controls ($n=20$) were assessed. The automated tortuosity measure was compared to a manual grading one, obtaining a moderate correlation (Spearman’s rank correlation coefficient = $0.49$, $p=0.0008$). The new tortuosity index was significantly higher in post-LASIK patients with ocular pain than in control patients ($p=0.001$), while no significant differences were detected with manual measurement ($p>0.28$). The tortuosity quantification was positively correlated with the ocular surface disease index (OSDI) and a numeric rating scale (NRS) assessing pain ($p=0.0012$ and $p=0.0051$, respectively). The results show good performance of the proposed automated methodology for the evaluation of corneal nerve tortuosity.