Vázquez Amanda, Blanco-Vázquez Marta, Martínez-Plaza Elena, Sobas Eva M, González-García María J, López-Miguel Alberto, Ortega Enrique, Enríquez-de-Salamanca Amalia, Calonge Margarita
From the IOBA (Institute of Applied Ophthalmobiology) (A.V., M.B.V., E.M.P., E.M.S., M.J.G.G., A.L.M., E.O., A.E.S., M.C.), Universidad de Valladolid (UVa), Valladolid, Spain; UDOVA (Pain Unit of Valladolid HURH-HCUV) (A.V., E.O.), National Health System, Castilla y Leon, Spain.
From the IOBA (Institute of Applied Ophthalmobiology) (A.V., M.B.V., E.M.P., E.M.S., M.J.G.G., A.L.M., E.O., A.E.S., M.C.), Universidad de Valladolid (UVa), Valladolid, Spain.
Am J Ophthalmol. 2025 Apr 17;276:170-185. doi: 10.1016/j.ajo.2025.04.004.
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.
慢性神经性眼痛(NOP)可在准分子激光原位角膜磨镶术(LASIK)后与慢性干眼(DE)同时出现,但其具体特征仍知之甚少。本研究旨在比较LASIK术后同时发生DE和NOP的患者与仅发生DE的患者以及无症状LASIK患者的临床特征,以促进NOP的诊断。
前瞻性横断面“病例对照”比较研究。一项纳入89名受试者的LASIK术后研究包括3组:34名发生NOP和DE的患者(NOP-DE组)、25名仅发生DE的患者(DE组)和30名无症状受试者(对照组)。评估包括临床病史和症状问卷(眼表疾病指数、改良Sjögren综合症状问卷、数字评分量表、威尔士干眼疼痛评分量表)、焦虑和抑郁评估(医院焦虑抑郁量表)、泪膜稳定性(渗透压和泪膜破裂时间)和泪液分泌(Schirmer试验)以及眼表完整性。使用贝尔蒙特非接触式眼压计测量角膜机械和热敏感度阈值,而使用科谢-博内眼压计在局部麻醉前后评估触觉敏感度阈值。使用共聚焦显微镜(IVCM)评估中央角膜基底神经丛特征和树突状细胞密度。进行组间比较和相关性分析。
与DE组相比,NOP-DE组患者在改良Sjögren综合症状问卷中表现出明显更多的DE症状(P = 0.019),在数字评分量表和威尔士干眼疼痛评分量表上疼痛程度更高,眼部润滑剂使用增加(P = 0.003),焦虑和抑郁问卷病理结果患者的频率更高(P < 0.001),以及中枢敏化综合征的患病率更高(P < 0.001)。此外,NOP-DE患者在局部麻醉后表现出更高的角膜触觉敏感度(P = 0.002)。IVCM显示,与无NOP的DE患者相比,NOP-DE患者的基底神经丛神经密度更低(P = 0.049),微神经瘤密度更高(P = 0.008)。大多数神经指标与临床参数呈中度至高度相关。
麻醉后角膜触觉敏感度持续较高、神经密度降低以及中央角膜微神经瘤密度增加可能作为确诊LASIK术后慢性DE患者NOP的诊断指标。这些发现强调了将这些测量纳入临床评估以提高诊断准确性并指导该患者群体管理策略的潜在效用。