Ocular Pain Assessment Survey Research Articles

Neuropathic Corneal Pain: Tear Proteomic and Neuromediator Profiles, Imaging Features, and Clinical Manifestations

To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients. Cross-sectional study. Twenty NCP patients and twenty age-matched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer's test, tear break-up time, corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires, as well as IVCM examinations for corneal nerves, microneruomas, epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. Burning and sensitivity to light were the two most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicle-associated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in the NCP patients. The top 10 dysregulated biological pathways in NCP include neurotoxicity, axonal signaling, wound healing, neutrophil degradation, apoptosis, thrombin signaling mitochondrial dysfunction, RHOGDI and P70S6K signaling pathways. Compared to controls, the NCP cohort presented with significantly decreased corneal sensitivity (P<0.001), decreased corneal nerve fiber length (P=0.003), corneal nerve fiber density (P=0.006), nerve fiber fractal dimension (P=0.033), as well as increased in corneal nerve fiber width (P=0.002), increased length, total area and perimeter of microneuromas (P<0.001, P<0.001, P=0.019), smaller corneal epithelial size (P=0.017), and higher nerve growth factor level in tears (p=0.006). These clinical manifestations, imaging features, and molecular characterizations would contribute to the diagnostics and potential therapeutic targets for NCP.

Characteristics of the retina and choroid in fibromyalgia patients and their correlation with disease severity and quality of life

BackgroundTo evaluate retinal and choroidal characteristics of fibromyalgia (FM) patients using spectral-domain optical coherence tomography (SD-OCT), to compare them with healthy controls, and to determine the correlation of these measurements with disease severity and quality of life. MethodsThirty-nine eyes of 39 patients with FM and 44 eyes of 44 age‐ and sex‐matched healthy subjects were enrolled. The retinal nerve fiber layer (RNFL), central macular thickness (CMT), and choroidal thickness (CT) measurements of the subjects were obtained using SD-OCT (Maestro, Topcon Co. Tokyo, Japan), choroidal vascular index (CVI) was calculated by using the binarization method and the results were compared. Disease duration (DD), widespread pain index (WPI), symptom severity scale (SSS), visual analog scale (VAS), ocular pain assessment survey (OPAS), FM impact questionnaire (FIQ), European Quality of Life-5 Dimensions-3 level (EQ-5D-3 L), European Quality VAS score (EQ-VAS) and use of pregabalin were recorded. Correlations between the SD-OCT results and the FM parameters were evaluated. ResultsNo significant difference was found in terms of age and gender (p = 0.612, p = 0.244 respectively). Patients in the FM group had significantly thinner RNFL superior quadrant and CT (p = 0,009 and p < 0.001, respectively). CVI was significantly higher in the FM group (p < 0.001). There was an inverse correlation between OPAS and CT (r = -0.379, p = 0.027) and between VAS and CVI (r = -0.398, p = 0.020). The use of pregabalin had no effect on SD-OCT (p > 0.05). ConclusionPatients with FM demonstrated reduced RNFL superior quadrant and CT and increased CVI. Ocular and general body pain in FM was found to be associated with SD-OCT.

Reliability and validity of the Japanese version of the Ocular pain assessment survey (OPAS-J)

This study aimed to determine the reliability and validity of the Japanese version of the Ocular Pain Assessment Survey (OPAS-J) to measure ocular pain and quality of life. A multi-institutional cross-sectional study was conducted on participants with and without ocular pain. The Wong–Baker FACES® Pain Rating Scale served as the gold standard for measuring the intensity of ocular pain. Sixty-four participants who visited two clinics located in Japan between May 2019 and October 2019 were included in the study. The OPAS was translated and culturally adapted to Japanese. The internal consistency of the OPAS-J was assessed using Cronbach’s alpha coefficient. Twenty-four (37.5%) and 40 (62.5%) participants were classified as having ocular pain and no ocular pain, respectively. All dimensions of the OPAS-J had good reliability, with a Cronbach’s alpha coefficient of 0.870 for ocular pain intensity over the past 24 h and 0.874, 0.899, 0.874, 0.871, and 0.876 for ocular pain intensity over the past 2 weeks, non-ocular pain, interference with quality of life, aggravating factors, and associated factors, respectively. The OPAS-J is a reliable and responsive tool that can be used to quantify ocular pain intensity.

Neuropathic corneal pain impacts patient's quality‐of‐life dimensions more than dry eye disease

AbstractPurpose: To compare the perception of ocular pain in patients with neuropathic corneal pain (NCP) and dry eye disease (DED), and to measure its impact on quality‐of‐life (QoL) dimensions (physical, psychological, social).Methods: A retrospective, cross‐sectional study, comparative study was conducted, including NCP (N = 119) and DED (N = 43) patients. Demographic features, ocular pain assessment survey (OPAS), and ocular surface disease index (OSDI) scores were reviewed. The OPAS comprises physical (vision‐related), social and psychological dimensions of QoL through six items.Results: The mean age of DED and NCP were 56.3 ± 15.7 and 56.2 ± 16.0 years, respectively (p = 0.966). The mean pain intensity scores (scale 0–10) in the last 24 h and 2 weeks were 2.04 ± 2.68 in DED patients and 5.03 ± 3.22 in NCP (p &lt; 0.01) and 2.08 ± 2.91 (DED) and 4.77 ± 3.51 (NCP; p &lt; 0.01) respectively. The interference of pain on QoL for DED and NCP patients was: reading/computer (DED 3.33 ± 3.24, NCP 5.54 ± 3.46, p = 0.003), driving/TV (DED 3.08 ± 3.28, NCP 4.59 ± 3.32, p = 0.024) for physical (visual related) dimension and Gen Act (DED 2.04 ± 2.77, NCP 3.87 ± 3.04, p = 0.001); Mood (DED 3.04 ± 3.39, NCP 5.66 ± 3.48 p = 0.001); Sleep (DED 2.32 ± 3.28, NCP 3.46 ± 3.18, p = 0.014) for the psychological dimension; enjoying life/social relations (DED 2.80 ± 3.26, NCP 5.15 ± 3.50, p = 0.001) for the social dimension of QoL. While pain had no significant impact on the visual dimension of QoL in DED (R = 0.14; p = 0.25), it had a significant impact in NCP patients (R = 0.41; p = 0.001). No significant difference in gender was resulting in any QoL dimension (p &gt; 0.05).Conclusion: Pain in patients with NCP has a more pronounced interference with physical, psychological, and social dimensions of QoL as compared to patients with DED. The vision‐related dimension of QoL is impacted by pain in NCP, but not in DED.

Impact of Peripheral and Corneal Neuropathy on Markers of Ocular Surface Discomfort in Diabetic Chronic Kidney Disease.

There is a reduction in corneal nerve fiber density and length in type 2 diabetes mellitus with chronic kidney disease compared with type 2 diabetes mellitus alone; however, this difference does not result in worse ocular surface discomfort or dry eye disease. This study aimed to determine the clinical impact of corneal nerve loss on ocular surface discomfort and markers of ocular surface homeostasis in people with type 2 diabetes mellitus without chronic kidney disease (T2DM-no CKD) and those with type 2 diabetes mellitus with concurrent chronic kidney disease (T2DM-CKD). Participants were classified based on estimated glomerular filtration rates into two groups: T2DM-CKD (n = 27) and T2DM-no CKD (n = 28). There was a significant difference between the T2DM-CKD and T2DM-no CKD groups in corneal nerve fiber density (14.9 ± 8.6 and 21.1 ± 7.1 no./mm 2 , respectively; P = .005) and corneal nerve fiber length (10.0 ± 4.6 and 12.3 ± 3.7 mm/mm 2 , respectively; P = .04). Fluorescein tear breakup time was significantly reduced in T2DM-CKD compared with T2DM-no CKD (8.1 ± 4.4 and 10.7 ± 3.8 seconds, respectively; P = .01), whereas ocular surface staining was not significantly different (3.5 ± 1.7 and 2.7 ± 2.3 scores, respectively; P = .12). In terms of ocular surface discomfort, there were no significant differences in the ocular discomfort score scores (12.5 ± 11.1 and 13.6 ± 12.1, respectively; P = .81) and Ocular Pain Assessment Survey scores (3.3 ± 5.4 and 4.3 ± 6.1, respectively; P = .37) between the T2DM-CKD and T2DM-no CKD. The current study demonstrated that corneal nerve loss is greater in T2DM-CKD than in T2DM-no CKD. However, these changes do not impact ocular surface discomfort or markers of ocular surface homeostasis.

Developing a Measure to Quantify Ocular Pain Postoperatively: The Adaptation of the Ocular Pain Assessment Survey.

Purpose Since quantification and communication of ocular pain is important for a healthier patient follow-up and postoperative guidance, reliable measures like the Ophthalmic Pain Assessment Survey (OPAS) are needed to assess the outcome and management of different operations. To address that need, we carried out the adaptation of OPAS into Turkish to reach different age groups and backgrounds, widening the use of OPAS on patients who underwent an ophthalmic operation. Methods We used back-translation method and achieved cultural adaptation through content validity scoring by 5 independent ophthalmologists. The survey is then administered three times: preoperatively, postoperatively within 24 hours, and finally a week later in the follow-up visit. Validity is measured in comparison to Visual Analog Scale using Spearman's correlation coefficient and reliability is measured using Cronbach's alpha. Factor analysis is performed by principal component analysis and rotation is performed using Varimax method when necessary. Results We reached a total of 132 patients with a mean age of 64.2 years. Most of them underwent phacoemulsification (n = 83), followed by PRK (n = 37). Overall, the T-OPAS demonstrated good reliability (mean C. alpha: 0.830) and its correlation with the VAS was especially high (S. coeff. >0.5) in the first three sections in all three surveys. Factor analysis yielded 5 subscales, allowing us to shape the final form of T-OPAS. Conclusion Through this adaptation of OPAS into a foreign language, we present a reliable and valid tool for postoperative pain quantification, allowing objective measurement of pain in different populations such as the elderly.

Ocular pain in ocular graft-versus-host disease patients with neurotrophic keratopathy

PurposeNeurotrophic keratopathy (NK) is a degenerative disorder of the cornea characterized by decreased sensory innervation, epitheliopathy, and impaired epithelial healing. In this study, we assessed ocular pain and quality-of-life-related parameters in ocular graft-versus-host disease (oGVHD) patients with and without NK. MethodsWe included 213 oGVHD patients in this retrospective study, including 29 patients with NK assessed by the Cochet-Bonnet esthesiometer. We evaluated their records for ocular pain assessment survey (OPAS) scores and clinical parameters, including corneal sensation, corneal fluorescein staining (CFS) score, Schirmer's test, tear break-up time (TBUT), and ocular surface disease index (OSDI) score. ResultsoGVHD patients with NK had lower corneal sensation (3.4 ± 1.4 vs. 5.9 ± 0.3; p < 0.0001), higher CFS scores (6.4 ± 4.2 vs. 4.7 ± 4.0; p = 0.01), and lower TBUT scores (1.2 ± 2.1 vs. 2.2 ± 3.1; p = 0.08) compared to oGVHD patients without NK and additionally had significantly higher ocular pain intensity scores (OPAS 24-h average eye pain intensity: 2.0 ± 2.8 vs. 1.1 ± 1.9; p = 0.03). Patients with NK more commonly reported burning (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.021) and sensitivity to light (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.049) as compared to patients without NK. ConclusionClinical signs of ocular surface disease are worse in oGVHD patients with NK compared to oGVHD patients without NK. These patients additionally experience higher intensity ocular pain and lower quality-of-life-related parameters.

Efficacy of Intense Pulsed Light Combined Blood Extract Eye Drops for Treatment of Nociceptive Pain in Dry Eye Patients.

Purpose: To investigate the efficacy of intense pulsed light (IPL) combined with deproteinized calf blood extract (DCBE) eye drops for dry eye disease (DED) patients with nociceptive ocular pain. Methods: In this prospective, one-center, interventional study, 23 subjects with DED and ocular pain were treated with a combination of IPL and DCBE eye drops for four sessions at a four-week interval. Subjective and objective assessments on nociceptive pain and dry eye were examined and analyzed. Results: The visual analog scale (VAS), ocular surface disease index, ocular pain assessment survey (OPAS), patient health questionnaire-9 items, generalized anxiety disorder (GAD-7), Athens insomnia scale, corneal fluorescein staining score, meibomian gland secretion quality, and expressibility scores were significantly reduced after the treatment. Tear break-up time and Schirmer I test increased significantly. The brand density of corneal nerves and neuropeptide substance P also significantly increased. OPAS, GAD-7, meibomian gland secretion quality, and expressibility scores were essential factors affecting the VAS changes. Conclusions: IPL combined with DCBE drop therapy was effective for DED patients with ocular pain. With such treatment, both DED symptoms and the sensation of ocular pain may be improved.

Semiautomated and Automated Quantitative Analysis of Corneal Sub-Basal Nerves in Patients With DED With Ocular Pain Using IVCM.

PurposeInvestigate the correlation and agreement between the results of semiautomated and fully automated quantitative analysis of the corneal sub-basal nerve plexus (SNP) in patients with dry eye disease (DED) with ocular pain using in vivo confocal microscopy (IVCM).MethodA total of 50 voluntary participants were enrolled in this study, i.e., 25 DED patients with ocular pain and 25 healthy controls. Each patient underwent an evaluation of ocular symptoms that utilized: the Ocular Surface Disease Index (OSDI), the Ocular Pain Assessment Survey (OPAS), the tear film breakup time (TBUT) test, the Schirmer test, corneal staining, and IVCM. Five SNP images of the cornea of each eye were selected and analyzed using a semiautomated analysis software (NeuronJ) and a fully automated method (ACCMetrics) to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL).ResultsThe intraclass correlation coefficient (ICC) of the CNFD (0.460 [0.382–0.532], p < 0.001), CNBD (0.608 [0.545–0.665], p < 0.001), and CNFL (0.851 [0.822–0.875], p < 0.001) represents the repeatability and consistency of measurements by the NeuronJ and ACCMetrics software. The CNFL values (r = 0.881, p < 0.001) obtained using the two methods have extremely high correlation, and similarly, the CNFD values (r = 0.669, p < 0.001) and CNBD values (r = 0.703, p < 0.001) are highly correlated. The CNFL had the biggest area under the curve (AUC; 0.747 [0.700–0.793], p < 0.001) when using ACCMetrics. In DED patients with ocular pain, the mean CNFD values for semiautomated and fully automated quantization were 23.5 ± 8.1 and 23.8 ± 8.6 n/mm2; the mean CNBD values were 46.0 ± 21.3, 35.7 ± 23.3 n/mm2; and the mean CNFL values were 19.3 ± 4.3 and 15.2 ± 3.8 mm/mm2, which were significantly lower than healthy subjects (p < 0.001).ConclusionThere is a significant correlation between the measurements obtained via ACCMetrics and NeuronJ, especially for CNFL, which can be considered as the primary indicator in the diagnosis of DED with ocular pain. The SNP of the disease was significantly lower than that of healthy subjects.

Concurrent ocular pain in patients with neurotrophic keratopathy

PurposeTo illustrate that ocular pain may occur in patients with neurotrophic keratopathy (NK) that typically are thought to lack symptoms of discomfort, and that aa subset of these patients may also present with neuropathic corneal pain (NCP). MethodRetrospective Case series of 7 stage 1 NK patients who presented with concurrent ocular pain, as confirmed by clinical examination, proparacaine challenge test, and in vivo corneal confocal microscopy (IVCM). Records were assessed for results of ocular surface disease index (OSDI), pain on visual analog scale (VAS), ocular pain assessment survey (OPAS), best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS) score, and IVCM findings. IVCM findings were compared to that of 20 healthy reference controls. ResultsMean age of patients was 63.7 ± 11.6 (range 44–76) years and 56.9 ± 8.6 (range 42–74) years in reference controls (p = 0.11). At presentation, ocular discomfort was 8.0 ± 1.3 (range 7–10) on VAS and mean OSDI scores were 72.26 ± 6.81 (range 62.50–79.54). Mean BCVA was 20/40, and mean CFS scores were 3.43 ± 0.79 (range 2–4) on the Oxford scale. IVCM analysis showed significant decrease in mean total, main and branch nerve densities in ranges consistent with NK as compared to normal controls (p < 0.001 for all), increased dendritiform cell density in three patients (p < 0.001), and the presence of microneuromas in six of the patients. ConclusionPatients with NK are thought to present with hypoesthesia. However, nerve damage and inflammation, which play a role in the development of NK may result in the development of chronic ocular pain, such as NCP, resulting in potential underdiagnosis of either disease.

Low-dose naltrexone is effective and well-tolerated for modulating symptoms in patients with neuropathic corneal pain

PurposeNeuropathic corneal pain (NCP) is caused by damage or disease of the somatosensory nervous system that innervates the cornea and presents with symptoms of pain or persistent unpleasant sensations, such as burning, dryness, or light sensitivity. This retrospective study aims to assess the efficacy and tolerability of low-dose naltrexone (LDN) in refractory NCP patients. MethodsFifty-nine NCP patients with a centralized component treated with oral LDN 4.5 mg at bedtime for at least four weeks were identified. Thirty out of 59 patients who had a baseline pain score ≥4 on the visual analogue scale had completed the ocular pain assessment survey (OPAS) and presented persistent pain, despite instillation of topical anesthetic drops, were included. Changes in pain scores, comorbidities, side effects, among others, were analyzed. Change in ocular pain scores (scale 0–10) and quality of life (QoL) scores (scale 0–100%) were the main endpoints. ResultsMean age (years ± SD) was 45.60 ± 19.30 with a white (80.00%) female (73.33%) predominance. Duration of LDN use was 14.87 ± 11.25 months, and the duration of NCP before treatment was 17.53 ± 17.29 months. Eight patients used LDN as a monotherapy, whereas the remaining used it as an adjunct therapy. LDN resulted in a 49.22% decrease in mean pain score from 6.13 ± 1.93 to 3.23 ± 2.60 (p < 0.001). Mean QoL scores by the OPAS were 5.84 ± 2.57 at the first visit and improved to 3.77 ± 2.91 at the last visit (p = 0.023). Common side effects were vivid dreams, headaches, and stomachache. ConclusionLDN was effective and well-tolerated for NCP treatment.

Topical TRPM8 Agonist for Relieving Neuropathic Ocular Pain in Patients with Dry Eye: A Pilot Study.

Background: Activation of TRPM8, a cold-sensing receptor located on the cornea and eyelid, has the potential to relieve the neuropathic ocular pain (NOP) in dry eye (DE) by inhibiting other aberrant nociceptive inputs. We aimed to investigate the effect of a topical TRPM8 agonist, cryosim-3 (C3), on relieving DE-associated NOP. Methods: We conducted a prospective pilot study of 15 patients with DE-associated NOP. These patients applied topical C3 to their eyelid, 4 times/day for 1 month. The patients underwent clinical examinations. They also completed the Ocular Pain Assessment Survey (OPAS), which is a validated questionnaire for NOP, at baseline, 1 week, and 1 month after treatment. Result: At 1 week, the OPAS scores of eye pain intensity, quality of life (driving/watching TV, general activity, sleep, and enjoying life/relations with other people), and associated factors (burning sensation, light sensitivity, and tearing) improved. The total OPAS scores of eye pain intensity, quality of life, and associated factors remained improved at 1 month. The Schirmer test scores also improved at 1 month. Conclusion: TRPM8 agonist (C3) could be a novel agent for treating patients with DE-associated NOP who are unresponsive to conventional treatments.

Treatment Response to Gabapentin in Neuropathic Ocular Pain Associated with Dry Eye.

Purpose: To investigate the response to gabapentin treatment in patients with dry eye (DE) accompanied by features of neuropathic ocular pain (NOP), and to analyze the differences between clinical manifestations of the groups according to treatment response. Methods: We retrospectively reviewed the records of 35 patients with DE accompanied by NOP features and obtained information on their medical history and previous ocular history. The patients underwent clinical examinations of the tear film, ocular surface, and meibomian gland and completed the Ocular Pain Assessment Survey (OPAS). One month after treatment with topical eye drops, add-on of gabapentin treatment was determined according to the Wong–Baker FACES Pain Rating Scale (WBFPS). A reduction of 2 points or more on the WBFPS was considered a positive treatment response. Enrolled patients were divided into three groups according to the treatment response: topical treatment response group (group 1, n = 11); gabapentin response group (group 2, n = 13); and gabapentin non-response group (group 3, n = 11). The medical history, clinical parameters, and OPAS scores were compared between groups. Results: The incidence of systemic comorbidities was higher in group 2 than in other groups. The corneal staining scores were lower in groups 2 and 3 than in group 1. Among the treatment response groups, group 2 showed improvements in OPAS scores of ocular pain severity, pain other than eyes, and quality of life, while group 1 showed improved OPAS scores of ocular pain severity and ocular associated factors. Group 2 exhibited lower scores of pains aggravated by mechanical and chemical stimuli than group 3. Conclusions: Gabapentin could be effective in patients who have systemic comorbidity and less pain evoked by mechanical and chemical stimuli for the treatment of DE patients with NOP, which is refractory to topical treatment.

Clinical characteristics of dry eye with ocular neuropathic pain features: comparison according to the types of sensitization based on the Ocular Pain Assessment Survey

BackgroundTo compare the clinical characteristics of dry eye patients with ocular neuropathic pain features according to the types of sensitization based on the Ocular Pain Assessment Survey (OPAS).MethodsCross-sectional study of 33 patients with dry eye and ocular neuropathic pain features. All patients had a comprehensive ophthalmic assessment including detailed history, the intensity and duration of ocular pain, the tear film, ocular surface, and Meibomian gland examination, and OPAS. Patients with < 50% improvement in pain intensity after proparacaine challenge test were assigned to the central-dominant sensitization group (central group) and those with ≥50% improvement were assigned to the peripheral-dominant sensitization group (peripheral group). All variables were compared between the two groups.ResultsNo significant differences were observed in age, sex, underlying diseases, history of ocular surgery, duration of ocular pain, tear film, ocular surface and Meibomian gland parameters (all p > 0.05). Ocular pain and non-ocular pain severity and the percentage of time spent thinking about non-ocular pain were significantly higher in the central group than in the peripheral group (all p < 0.05). Central group complained more commonly of a burning sensation than did the peripheral group (p = 0.01).ConclusionsPatients with central-dominant sensitization may experience more intense ocular and non-ocular pain than the others and burning sensation may be a key symptom in those patients.

Efficacy and tolerability of nortriptyline in the management of neuropathic corneal pain

PurposeNeuropathic corneal pain (NCP) is a recently acknowledged disease entity. However, there is no consensus in potential treatment strategies, particularly in patients with a centralized component of pain. This study aims to assess the efficacy and tolerability of the tricyclic antidepressant, nortriptyline, among NCP patients. MethodsPatients with clinically diagnosed NCP and a centralized component of pain, treated with oral nortriptyline, who had recorded pain scores as assessed by the ocular pain assessment survey at the first and last visit were included. Patients were excluded if they had any other ocular pathology that might result in pain or had less than 4 weeks of nortriptyline use. Demographics, time between visits, concomitant medications, systemic and ocular co-morbidities, duration of NCP, side effects, ocular pain scores, and quality of life (QoL) assessment were recorded. ResultsThirty patients with a mean age of 53.1 ± 18.5 were included. Male to female ratio was 8:22. Mean ocular pain in the past 24 h improved from 5.7 ± 2.1 to 3.6 ± 2.1 after 10.5 ± 9.1 months (p < 0.0001). Twelve patients (40.0%) had equal to or more than 50% improvement, 6 patients (20.0%) had 30–49% improvement, 6 patients (20.0%) had 1–29% improvement, 4 patients (13.3%) did not improve, while 2 patients (6.7%) reported increase in pain levels. Mean QoL improved from 6.0 ± 2.5 to 4.3 ± 2.4 (p = 0.019). Eight patients (26.6%) discontinued treatment due to persistent side effects, despite improvement by 22.4%. ConclusionNortriptyline was effective in relieving NCP symptoms in patients with centralized component and insufficient response to other systemic and topical therapies who tolerated the drug for at least 4 weeks. Nortriptyline may be used in the management of patients with NCP.

Comparison of clinical characteristics of post-refractive surgery-related and post-herpetic neuropathic corneal pain

PurposeTo compare the clinical characteristics and in vivo confocal microscopy (IVCM) findings of patients with neuropathic corneal pain (NCP) due to refractive surgery (RS-NCP) and herpetic eye disease (H-NCP) to controls. MethodsSixteen patients with RS-NCP and 7 patients with H-NCP, and 37 healthy reference age- and sex-matched healthy controls were included to the study. The medical records were reviewed for demographic features, detailed disease history, ocular surface disease index (OSDI), ocular pain assessment survey (OPAS) scores. IVCM images of patients were analyzed and compared to reference controls by two masked observers. ResultsThe mean pain intensity score for the last 24 h (5.1 ± 2.4 vs. 3.9 ± 1.2; p = 0.27), last 2 weeks (6.1 ± 2.5 vs. 4.8 ± 2.3; p = 0.13) for RS-NCP vs. H-NCP respectively, and quality of life scores (p = 0.23) were similar in both groups. Quality of life, especially mood (p = 0.06) and enjoying life/relations to others (p = 0.10) were affected in both groups, but were not statistically significant between groups. The mean total nerve density was lower in RS-NCP (5,702.4 ± 4,599.0 μm/mm2) compared to their respective controls (26,422.8 ± 4,491.0; p < 0.001) and in the H-NCP group (2,149.5 ± 2,985.9) compared to their respective controls (22,948.8 ± 3,169.0; p < 0.001). Alterations in DC density were similar between all groups (38.3 ± 48.0 cells/mm2 in RS-NCP, 61.0 ± 76.9 in H-NCP, p = 0.95). ConclusionNeuropathic corneal pain patients due to refractive surgery show similar clinical characteristics, pain levels, quality of life impact, and IVCM findings as patients with NCP due to herpetic eye disease.

PMU135 PATIENT-REPORTED OUTCOME MEASURES IN PATIENTS WITH CHRONIC OCULAR SURFACE PAIN : A LITERATURE REVIEW

Chronic ocular surface pain (COSP) is a persistent eye pain at the ocular surface lasting for a period longer than 3 months that interferes with regular daily activities, and is severely impacting patients’ health related quality of life (HRQoL).The aim of this study was to review the suitability of existing patient-reported outcome measures (PROMs) for use in clinical trials, assessing potential new therapies of COSP. Literature searches were performed in Medline and Embase using Ovid SP platform until March 2019. Specific search terms were used to identify studies assessing QoL in patients experiencing ocular pain. The review was complemented by searching relevant trials using PRO endpoints in ocular pain on clinicaltrials.gov. The measurement characteristics of the identified tools were reviewed in line with FDA’s 2009 PRO Guidance. A total of 1,130 abstracts were identified for initial screening and 177 were selected for full text review. In total 16 tools were identified, and of these, only four (Ocular Pain Assessment Survey (OPAS), Eye Sensation Scale (ESS), Neuropathic Pain Symptom Inventory (NPSI)-Eye and Brief Ocular Discomfort Inventory (BODI) specifically measured ocular pain. OPAS and ESS were originally developed for measuring ocular pain, whereas NPSI-Eye and BODI are modified versions of generic pain scales. As OPAS assesses the most critical HRQoL impacts of COSP such as impact on visual functioning, mood, sleep in addition to severity and type of pain assessment, it appears being the most adequate tool for its usage in future clinical trials. Among the PROMs identified for usage in future COSP clinical trials, OPAS appears to be the most suitable one. Further investigation is needed to ensure that OPAS is an appropriate and well-validated tool to assess new treatments for COSP in accordance with regulatory requirements.

Validity and Reliability of a Novel Ocular Pain Assessment Survey (OPAS) in Quantifying and Monitoring Corneal and Ocular Surface Pain

To validate the Ocular Pain Assessment Survey (OPAS), specifically designed to measure ocular pain and quality of life for use by eye care practitioners and researchers. A single-center cohort study was conducted among patients with and without corneal and ocular surface pain at initial and follow-up visits over a 6-month period. The content of the OPAS was guided by literature review, a body of experts, and incorporating conceptual frameworks from existing pain questionnaires. The Wong-Baker FACES Pain Rating Scale served as the gold standard for measuring the intensity of ocular pain. A total of 102 patients aged 18 to 80 years completed the OPAS at the initial visit. A total of 21 patients were followed up after treatment. Indices of validity and internal consistency (Spearman's rank-order, rs, or Pearson's correlation coefficients, rp), and coefficient of reliability (Cronbach's α) were determined in addition to equivalence testing, exploratory factor analysis (EFA), and diagnostic analysis. Eye pain intensity was the primary outcome measure, and interference with quality of life (QoL), aggravating factors, associated factors, associated non-eye pain intensity, and self-reported symptomatic relief were the secondary outcome measures. The OPAS had criterion validity at both initial (rs= 0.71; n= 102; P < 0.01) and follow-up visits (rs= 0.97; n= 21; P < 0.01). Equivalence tests yielded OPAS and gold standard equivalence for both the initial and follow-up visits. The EFA supported 6 subscales (eye pain intensity at 24 hours and 2 weeks, non-eye pain intensity, QoL, aggravating factors, and associated factors) confirming multidimensionality. Cronbach's α >0.83 for all subscales established strong internal consistency, which correlated with the gold standard, including 24-hour eye pain intensity and QoL interference scores (rp= 0.81, 0.64, respectively P < 0.001). At follow-up, reduction in pain scores was accompanied by improvement in all dimensions of the OPAS. Percentage change in QoL correlated to percentage change in the gold standard (rp= 0.53; P< 0.05). The OPAS was sensitive (94%), specific (81%), and accurate (91%), with a diagnostic odds ratio>50. The OPAS is a valid, reliable, and responsive tool with strong psychometric and diagnostic properties in the multidimensional quantification of corneal and ocular surface pain intensity, and QoL.

185 Severe thrombocytopenia but not neutropenia predicts infection complications during azacitidine therapy in high risk MDS patients

To illustrate that ocular pain may occur in patients with neurotrophic keratopathy (NK) that typically are thought to lack symptoms of discomfort, and that aa subset of these patients may also present with neuropathic corneal pain (NCP).Retrospective Case series of 7 stage 1 NK patients who presented with concurrent ocular pain, as confirmed by clinical examination, proparacaine challenge test, and in vivo corneal confocal microscopy (IVCM). Records were assessed for results of ocular surface disease index (OSDI), pain on visual analog scale (VAS), ocular pain assessment survey (OPAS), best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS) score, and IVCM findings. IVCM findings were compared to that of 20 healthy reference controls.Mean age of patients was 63.7 ± 11.6 (range 44–76) years and 56.9 ± 8.6 (range 42–74) years in reference controls (p = 0.11). At presentation, ocular discomfort was 8.0 ± 1.3 (range 7–10) on VAS and mean OSDI scores were 72.26 ± 6.81 (range 62.50–79.54). Mean BCVA was 20/40, and mean CFS scores were 3.43 ± 0.79 (range 2–4) on the Oxford scale. IVCM analysis showed significant decrease in mean total, main and branch nerve densities in ranges consistent with NK as compared to normal controls (p < 0.001 for all), increased dendritiform cell density in three patients (p < 0.001), and the presence of microneuromas in six of the patients.Patients with NK are thought to present with hypoesthesia. However, nerve damage and inflammation, which play a role in the development of NK may result in the development of chronic ocular pain, such as NCP, resulting in potential underdiagnosis of either disease.