Oral Gabapentinoids and Nerve Blocks for the Treatment of Chronic Ocular Pain.

PURPOSE: There is a recognition that nerve dysfunction can contribute to chronic ocular pain in some individuals. However, limited data are available on how to treat individuals with a presumed neuropathic component to their ocular pain. As such, the purpose of this study was to examine the efficacy of our treatment approaches to this entity. METHODS: A retrospective review of treatments and outcomes in individuals with chronic ocular pain that failed traditional therapies. RESULTS: We started eight patients on an oral gabapentinoid (gabapentin and/or pregabalin) as part of their pain regimen (mean age 46 years, 50% women). Two individuals reported complete ocular pain relief with a gabapentinoid, in conjunction with their topical and oral medication regimen. Three individuals noted significant improvements, one slight improvement, and two others no improvement in ocular pain with gabapentin or pregabalin. We performed periocular nerve blocks (4 mL of 0.5% bupivacaine mixed with 1 mL of 80 mg/mL methylprednisolone acetate) targeting the periocular nerves (supraorbital, supratrochlear, infratrochlear, and infraorbital) in 11 individuals (mean age 54 years, 36% women), 10 of whom had previously used a gabapentinoid without ocular pain improvement. Seven individuals experienced pain relief after nerve blocks that lasted from hours to months and four failed to benefit. Five of the individuals who experienced pain relief underwent repeat nerve blocks, weeks to months later. CONCLUSIONS: Approaches used to treat chronic pain outside the eye can be applied to ocular pain that is not responsive to traditional therapies.

Individuals with migraine have a different dry eye symptom profile than individuals without migraine.

BACKGROUND: Many individuals with migraine report symptoms of dry eye (DE). However, it is not known whether DE profiles are similar between individuals with and without migraine. To bridge this gap, we evaluated symptoms and signs of DE, including symptoms suggestive of nerve dysfunction, in a large group of individuals with DE symptoms, and compared profiles between individuals with migraine and those without migraine or headache. METHODS: Prospective cross-sectional study of individuals with DE symptoms seen at the Miami VA. RESULTS: Of 250 individuals, 31 met International Classification of Headache Disorders criteria for migraine based on a validated screen. Individuals with migraine were significantly younger (57 vs 62 years) and more likely to be female (26% vs 6%) than controls. Individuals with migraine had more severe DE symptoms and ocular pain compared with controls (mean Ocular Surface Disease Index 53.93 ± 21.76 vs 36.30 ± 22.90, p=0.0001; mean Neuropathic Pain Symptom Inventory modified for the Eye 39.39 ± 23.33 vs 21.86 ± 20.17, p=0.0001). The difference in symptom profile occurred despite similar ocular surface parameters between the groups. CONCLUSIONS: Individuals with migraine had a different DE symptom yet a similar DE sign profile when compared with controls without migraine. This suggests that DE symptoms in individuals with migraine may be driven by nerve dysfunction as opposed to ocular surface abnormalities.

Effect of non-invasive intranasal neurostimulation on tear volume, dryness and ocular pain.

PURPOSE: To evaluate the effect of one TrueTear session on change in tear volume and symptoms of dryness and ocular pain. METHODS: Retrospective interventional case series of patients seen in a dry eye clinic. Seventy-five individuals underwent an ocular surface examination and one session of neurostimulation. Outcome measures included objective change in tear volume measured via phenol red test, and subjective change in sensations of dryness and ocular pain measured on a 0-10 Numerical Rating Scale. RESULTS: The mean age of the 75 individuals was 59±13 years, and the majority were male (73%). Intranasal neurostimulation increased tear volume (mean 13.40±8.00 mm, p<0.0005) and reduced intensities of dryness (mean -2.85±2.79, p<0.0005) and ocular pain (mean -1.48±2.41, p<0.0005 for both). However, these effects were independent of one another as change in symptom report did not correlate with change in tear volume (r=-0.13, p=0.25 for dryness; r=0.07, p=0.56 for pain). In a multivariable model, the strongest predictors for increased tear volume were lower baseline tear volume (standardised beta (ß)=-0.50, p<0.0005) and absence of an autoimmune disease (ß=-0.36, p=0.001) (R2=0.30). The strongest predictors for reduced dryness and pain scores were lower baseline dryness and ocular pain scores. No complications related to neurostimulation were noted. CONCLUSION: Intranasal neurostimulation increased tear volume and reduced intensities of dryness and ocular pain, independently of one another.

Pregabalin Failed to Prevent Dry Eye Symptoms after Laser-Assisted in Situ Keratomileusis (LASIK) in a Randomized Pilot Study.

PURPOSE: Perioperative pregabalin administration has been found to reduce the risk of persistent pain after a variety of surgical procedures. However, this approach has not been tested in relation to eye surgery. As such, the purpose of this study was to evaluate whether perioperative pregabalin can reduce the presence of dry eye (DE) symptoms, including eye pain, six months after laser-assisted in situ keratomileusis (LASIK). METHODS: Prospective, masked, randomized single-center pilot study. Patients were treated with either pregabalin (oral solution of pregabalin 150 mg twice daily, first dose prior to surgery, continued for a total of 28 doses over 14 days) or placebo solution. The primary outcome was dry eye symptoms as measured by the Dry Eye Questionnaire 5 (DEQ-5). Secondary outcome measures included pain-related eye symptoms. RESULTS: In total, 43 individuals were enrolled in the study and randomized to pregabalin (n = 21) or placebo (n = 22). Of those, 42 individuals completed the final visit after six months of follow-up. Some differences were noted between the two groups at baseline, including a higher frequency of females in the pregabalin group. At 6-months, there were no significant differences in the percentage of patients with DE symptoms (DEQ5 ≥ 6, 57% vs. 33%, p = 0.14), DE symptom severity (DEQ5, 6.6 ± 5.0 vs. 4.5 ± 4.2, p = 0.14), ocular pain intensity (numerical rating scale, 1.10 ± 1.48 vs. 0.38 ± 0.97, p = 0.08), or neuropathic pain complaints (Neuropathic Pain Symptom Inventory-Eye, 2.81 ± 4.07 vs. 3.14 ± 5.85, p = 0.83) between the pregabalin and control groups. Ocular signs were likewise similar between the groups, and of note, did not correlate with DE symptoms. The strongest predictor of DE symptoms six months post-surgery was the presence of DE symptoms prior to surgery. CONCLUSIONS: Perioperative pregabalin did not reduce the frequency or severity of DE symptoms at a six month follow-up after LASIK in this small pilot study.

Dysfunctional Coping Mechanisms Contribute to Dry Eye Symptoms.

Dysfunctional coping behaviors, such as catastrophizing, have been implicated in pain severity and chronicity across several pain disorders. However, the impact of dysfunctional coping has not been examined under the context of dry eye (DE). This study evaluates relationships between catastrophizing and measures of DE, including pain severity and pain-related daily interference. The population consisted of patients seen at Miami Veterans Affairs eye clinic between April 2016 and October 2017. Patients filled out standardized questionnaires assessing symptoms of DE and eye pain, non-ocular pain, mental health, coping behaviors (Pain Catastrophizing Scale, PCS), and pain-related daily interference as a perceived impact on quality of life (Multidimensional Pain Inventory, Interference Subscale, MPI-Interference), and all patients underwent an ocular surface examination. In total, 194 patients participated, with a mean age of 58.8 ± 9.6 years, the majority being male, non-Hispanic, and black. PCS (catastrophizing) was correlated with DE symptom severity, including Dry-Eye Questionnaire 5 (DEQ5; r = 0.41, p < 0.0005), Ocular Surface Disease Index (OSDI; r = 0.40, p < 0.0005), and neuropathic-like eye pain (Neuropathic Pain Symptom Inventory-Eye (NPSI-Eye; r = 0.48, p < 0.0005). Most tear metrics, on the other hand, did not correlate with PCS. Linear regressions showed that PCS, non-ocular pain intensity, and number of pain conditions were significant predictors of DEQ5 (overall DE symptoms), while PCS and non-ocular pain intensity were predictors of NPSI-Eye scores, as were insomnia scores and analgesic use. In a separate analysis, PCS and DE symptoms (OSDI) associated with pain-related interference (MPI-Interference) along with non-ocular pain intensity, post-traumatic stress disorder (PTSD), number of pain conditions, and non-Hispanic ethnicity. These findings suggest that catastrophizing is not significantly related to signs of DE, but is strongly associated to pain-related symptoms of DE and daily interference due to pain.

Modification of the Neuropathic Pain Symptom Inventory for use in eye pain (NPSI-Eye).

Chronic eye pain, which has previously been assumed to be due to ocular surface abnormalities (ie, "dry eye [DE] disease"), has recently garnered attention as a potential indicator of neuropathic ocular pain in some patients. The purpose of this study was to evaluate the psychometric properties of a modified version of the Neuropathic Pain Symptom Inventory in individuals with eye pain (NPSI-Eye). Enrolled participants (n = 397) completed the NPSI-Eye, general pain severity questionnaires, DE symptom report, and psychological health indices. Participants also underwent mechanical pain sensitivity testing of the cornea, tear film assessment, and evaluation of the efficacy of anesthetic eye drops to relieve pain. Short-term test-retest reliability of the NPSI-Eye was excellent (intraclass correlation coefficient = 0.98, P < 0.001). Correlations between the NPSI-Eye and indicators of general eye pain were ≥0.65 (P < 0.001), whereas correlations between the NPSI-Eye and DE symptom severity and psychological health indices were lower (rho = 0.56, 0.32, 0.37; all P < 0.001). Individuals who reported little or no decrease in pain after anesthetic eye drops (hypothesized to indicate eye pain with at least partial central involvement) had significantly higher NPSI-Eye scores than participants whose eye pain was completely relieved by anesthetic (P < 0.05). Overall, our results support preliminary validation of the NPSI-Eye, yielding similar metrics to those reported in Bouhassira et al.'s original NPSI publication (2004). However, additional evaluation and refinement of some questions may be desirable, including the potential elimination of items that were not highly endorsed.

Resolution of pain with periocular injections in a patient with a 7-year history of chronic ocular pain.

PURPOSE: We report a case of a male patient with chronic ocular pain that resolved completely following peripheral nerve blocks. OBSERVATIONS: A 66-year-old male presented with a seven-year history of severe left eye pain and photophobia. The pain began after retinal detachment repair with scleral buckle placement. Previous treatments included topical (autologous serum tears, corticosteroids, diclofenac, cyclosporine) and oral (gabapentin, diclofenac) therapies with no pain relief. The patient's pain was so severe that he requested enucleation. After discussion, the decision was made to perform periocular nerve blocks. Prior to the procedure, the patient reported an average pain intensity of 8 out of 10 and photophobia daily. Following left supraorbital, supratrochlear, infraorbital and infratrochlear injections with bupivacaine and methylprednisolone, pain intensity and photophobia improved to 1-2 out of 10. One week later, repeat infraorbital and infratrochlear nerve blocks were given, after which time the patient reported complete resolution of symptoms that lasted for 7 months. Repeat nerve blocks were administered with repeat resolution of pain. There were no complications associated with the procedures. CONCLUSIONS AND IMPORTANCE: Chronic ocular pain can be a debilitating condition. Periorbital nerve blocks can provide pain relief and should be considered as a potential treatment option after medical management has failed.

Photophobia and sensations of dryness in patients with migraine occur independent of baseline tear volume and improve following botulinum toxin A injections.

BACKGROUND: To evaluate the efficacy of botulinum toxin A (BoNT-A) in reducing photophobia and dry eye symptoms in individuals with chronic migraine. Additionally, we aimed to evaluate tear film volume as a potential contributor to symptoms in these patients. METHODS: Retrospective review of 76 patients who received BoNT-A for chronic migraine between 23 August 2017 and 13 December 2017 at the Miami Veterans Affairs Medical Center Neurotoxin Clinic. Demographic data and all comorbidities were queried via chart review. Standardised validated surveys were administered to assess symptoms prior to and after BoNT-A injection. Preinjection tear volumes were obtained using the phenol red thread (PRT) test. RESULTS: Preinjection migraine, photophobia and dry eye symptom scores were all significantly correlated, p<0.05, and none were associated with preinjection PRT results. After BoNT-A, improvements in migraine, photophobia and dry eye symptoms were also significantly correlated, p<0.05 and similarly did not associate with preinjection PRT results. Photophobia scores significantly improved following BoNT-A, while dry eye symptoms significantly improved in those with severe symptoms at baseline (DEQ-5 score ≥12), p=0.027. In logistic regression analysis of all individuals with dry eye symptoms (DEQ-5 ≥6), individuals with more severe dry eye symptoms were more likely improve, OR 1.27, 95% CI 1.06 to 1.51, p<0.01. CONCLUSIONS: BoNT-A significantly improved photophobia in patients being treated for migraine and also improved dry eye symptoms in patients with severe symptoms at baseline, independent of baseline tear film volume. These improvements may be due to modulation of shared trigeminal neural pathways.

Epidemiology of Persistent Postsurgical Pain Manifesting as Dry Eye-Like Symptoms After Cataract Surgery.

PURPOSE: To evaluate the epidemiology of persistent postsurgical pain (PPP) manifesting as dry eye (DE)-like symptoms 6 months after surgery. METHODS: This single-center study included 119 individuals whose cataract surgeries were performed by a single surgeon at the Bascom Palmer Eye Institute and who agreed to participate in a phone survey 6 months after surgery. Patients were divided into 2 groups: the PPP group was defined as those with a Dry Eye Questionnaire-5 score ≥6 and without PPP as those with a Dry Eye Questionnaire-5 score <6 at 6 months after cataract surgery. RESULTS: Mean age of the study population was 73 ± 8.0 years; 55% (n = 66) were female. PPP was present in 34% (n = 41) of individuals 6 months after surgery. Factors associated with an increased risk of PPP were female sex [odds ratio (OR) = 2.68, 95% confidence interval (CI) = 1.20-6.00, P = 0.01], autoimmune disorder (OR = 13.2, CI = 1.53-114, P = 0.007), nonocular chronic pain disorder (OR = 4.29, CI = 1.01-18.1, P = 0.06), antihistamine use (OR = 6.22, CI = 2.17-17.8, P = 0.0003), antireflux medication use (OR = 2.42, CI = 1.04-5.66, P = 0.04), antidepressant use (OR = 3.17, CI = 1.31-7.68, P = 0.01), anxiolytic use (OR = 3.38, CI = 1.11-10.3, P = 0.03), and antiinsomnia medication use (OR = 5.28, CI = 0.98-28.5, P = 0.047). PPP patients also reported more frequent use of artificial tears (P < 0.0001), higher ocular pain levels (P < 0.0001), and greater neuropathic ocular pain symptoms, including burning (P = 0.001), wind sensitivity (P = 0.001), and light sensitivity (P < 0.0001). CONCLUSIONS: PPP in the form of persistent DE-like symptoms is present in approximately 34% of individuals 6 months after cataract surgery. The frequency of PPP after cataract surgery is comparable to that of other surgeries including laser refractive surgery, dental implants, and genitourinary procedures.

Epidemiology of Persistent Dry Eye-Like Symptoms After Cataract Surgery.

PURPOSE: To evaluate the frequency and risk factors for persistent postsurgical pain (PPP) after cataract surgery, defined as mild or greater dry eye (DE)-like symptoms 6 months after surgery. METHODS: This single-center study included 86 individuals who underwent cataract surgery between June and October 2016 and had DE symptom information available 6 months after surgery. Patients were divided into 2 groups: controls were defined as those without DE symptoms 6 months after surgery (defined by a Dry Eye Questionnaire 5 (DEQ5) score <6), cases were defined as those with mild or greater DE-like symptoms 6 months after surgery (DEQ5 ≥6). RESULTS: Mean age of the study population was 71 ± 8.6 years; 95% (n = 82) were men. DE-like symptoms were reported in 32% (n = 27) of individuals 6 months after cataract surgery; 10% (n = 8) reported severe symptoms (DEQ5 ≥12). Patients with DE-like symptoms after cataract extraction also had higher ocular pain scores and specific ocular complaints (ocular burning, sensitivity to wind and light) compared with controls with no symptoms. A diagnosis of nonocular pain increased the risk of DE-like symptoms after cataract surgery (odds ratio 4.4, 95% confidence interval 1.58-12.1, P = 0.005). CONCLUSIONS: Mild or greater PPP occurred in approximately 1/3 of individuals after cataract surgery. Prevalence of severe PPP is in line with that of refractive surgery, dental implants, and genitourinary procedures.

Epidemiology of discordance between symptoms and signs of dry eye.

BACKGROUND/AIMS: The frequent lack of association between dry eye (DE) symptoms and signs leads to challenges in diagnosing and assessing the disease. METHODS: Participants underwent ocular surface examinations to evaluate signs of disease and completed questionnaires to assess ocular symptoms, psychological status and medication use. To assess nociceptive system integrity, quantitative sensory testing (QST), including vibratory and thermal threshold measures and temporal summation of pain were obtained at the forearm and forehead. Correlations between DE discordance score (degree of discrepancy between symptom severity and DE signs) and patient characteristics were determined. Higher discordance scores indicated more symptoms than signs. RESULTS: 326 patients participated (mean age: 62 years; SD: 10 years; 92% men). Age was negatively correlated with DE discordance score (Pearson r=-0.30, p<0.0005), while mental health indices were positively correlated. Chronic pain elsewhere in the body (ie, non-ocular pain conditions) and intensity ratings of prolonged aftersensations of pain evoked by noxious hot and cold stimuli were also significantly correlated with DE discordance score. Multiple linear regression demonstrated that post-traumatic stress disorder and non-ocular pain intensity were important predictors of DE discordance score, Dry Eye Questionnaire-5 and Ocular Surface Disease Index and that DE discordance was also sensitive to QST as well. CONCLUSIONS: The present study provides evidence that the degree of discordance between DE symptom report and measurable signs of ocular surface disease is associated with comorbidities related to clinical pain and to hyperalgesia as demonstrated with QST. Understanding the epidemiology of DE discordance can aid in interpreting the DE exam and individualising treatment.

The Association of Dry Eye Symptom Severity and Comorbid Insomnia in US Veterans.

PURPOSE: To investigate the association between dry eye (DE) and insomnia symptom severity. METHODS: Cross-sectional study of 187 individuals seen in the Miami Veterans Affairs eye clinic. An evaluation was performed consisting of questionnaires regarding insomnia (insomnia severity index [ISI]) and DE symptoms, including ocular pain, followed by a comprehensive ocular surface examination. Using a two-step cluster analysis based on intensity ratings of ocular pain, the patient population was divided into two groups (high and low ocular pain groups: HOP and LOP). A control group was ascertained at the same time from the same clinic as defined by no symptoms of DE (Dry Eye Questionnaire 5 [DEQ5], <6). The main outcome measure was the frequency of moderate or greater insomnia in the DE groups. RESULTS: The mean age of the study sample was 63 years, and 93% were male. All insomnia complaints were rated higher in the HOP group compared with the LOP and control groups (P<0.0005). Most (61%) individuals in the HOP group experienced insomnia of at least moderate severity (ISI≥15) compared with the LOP (41%) and control groups (18%) (P<0.0005). Black race (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.2-6.0; P=0.02), depression severity (OR, 1.2; 95% CI, 1.1-1.3; P<0.0005), and DE symptom severity (DEQ5; OR, 1.1; 95% CI, 1.01-1.2; P=0.03) were significantly associated with clinical insomnia (ISI≥15) after controlling for potential confounders. CONCLUSIONS: After adjusting for demographics and medical comorbidities, we show that DE symptom severity is positively associated with insomnia severity.

Traumatic brain injury, dry eye and comorbid pain diagnoses in US veterans.

AIMS: The purpose of the study is to evaluate the relationship between dry eye (DE) and pain diagnoses in US veterans with and without traumatic brain injury (TBI). METHODS: Retrospective cohort study of veterans who were seen in the Veterans Administration Hospital (VA) between 1 January 2010 and 31 December 2014. Veterans were separated into two groups by the presence or absence of an International Classification of Diseases, Ninth Revision diagnosis of TBI and assessed for DE and other comorbidities. A dendrogram was used to investigate the linkage between TBI, DE, chronic pain and other comorbid conditions. RESULTS: Of the 3 265 894 veterans seen during the 5-year period, 3.97% carried a diagnosis of TBI. Veterans with TBI were more likely to have a diagnosis of DE compared with their counterparts without TBI (37.2% vs 29.1%, p<0.0005). The association was stronger between TBI and ocular pain (OR 3.08; 95% CI 3.03 to 3.13) compared with tear film dysfunction (OR 1.09; 95% CI 1.07 to 1.10). Those with TBI were also about twice as likely to have a diagnosis of chronic pain, headache, depression or post-traumatic stress disorder compared with their counterparts without TBI. Cluster analysis of TBI, DE and pain diagnoses of interest revealed that central pain syndrome, cluster headache, sicca syndrome, keratoconjunctivitis sicca and late effect of injury to the nervous system (as can be seen after TBI) were all closely clustered together. CONCLUSIONS: DE and pain disorders occur at higher frequencies in patients with a diagnosis of TBI, suggesting a common underlying pathophysiology.

Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia.

INTRODUCTION: "Dry eye" or "keratoconjunctivitis sicca" is a multifactorial disease estimated to have a worldwide prevalence of 5-33%. Conventional therapies targeting the ocular surface with artificial tears, anti-inflammatories, punctal closure, eyelid hygiene, and antibiotics do not provide relief in all patients, especially those with neuropathic-like ocular complaints (wind hyperalgesia and photophobia). We anticipated that ocular transcutaneous electrical nerve stimulation (TENS) would alleviate symptoms of ocular pain, photophobia, and dryness in these latter individuals. METHODS: All individuals who received electrical stimulation between May 10, 2016 and April 6, 2017 for the treatment of chronic ocular pain at the oculofacial pain clinic of the Miami Veterans Administration Hospital were included in this retrospective review. All patients had symptoms of dryness along with other neuropathic-like symptoms (e.g., photophobia) and minimal signs of tear dysfunction. Ocular pain intensity, symptoms of dryness, and light sensitivity were compared pre-treatment and five min post-treatment via a two-tailed paired Student's t-test. RESULTS: The use of TENS significantly reduced the mean pain intensity in both the right and left eyes five min after treatment compared to prior to treatment (p < 0.05, paired t-test). The use of TENS significantly decreased light sensitivity in both eyes (p < 0.05). The findings for symptoms of dryness, however, were equivocal with a significant decrease in the left eye but not the right (p < 0.05, paired t-test). DISCUSSION: Our data indicate that TENS may similarly provide analgesia in patients with dry eye symptoms as it does for many other chronic pain conditions. Furthermore, the noted effect on symptoms of photophobia and dryness suggest that all may be linked by similar trigeminal-thalamic-cortical pathways. Prospective studies with electrical stimulation of dry eye are needed to further elucidate its benefit and mechanism of action.

Modified open-access scheduling for new patient evaluations at an academic chronic pain clinic increased patient access to care, but did not materially reduce their mean cancellation rate: A retrospective, observational study.

STUDY OBJECTIVE: To determine if open-access scheduling would reduce the cancellation rate for new patient evaluations in a chronic pain clinic by at least 50%. DESIGN: Retrospective, observational study using electronic health records. SETTING: Chronic pain clinic of an academic anesthesia department. PATIENTS: All patients scheduled for evaluation or follow-up appointments in the chronic pain clinic between April 1, 2014, and December 31, 2015. INTERVENTIONS: Open-access scheduling was instituted in April 2015 with appointments offered on a date of the patient's choosing ≥1 business day after calling, with no limit on the daily number of new patients. MEASUREMENTS: Mean cancellation rates for new patients were compared between the 12-month baseline period prior to and for 7months after the change, following an intervening 2-month washout period. The method of batch means (by month) and the 2-sided Student t-test were used; P<0.01 required for significance. MAIN RESULTS: The new patient mean cancellation rate decreased from a baseline of 35.7% by 4.2% (95% confidence interval [CI] 1.4% to 6.9%; P=0.005); however, this failed to reach the 50% reduction target of 17.8%. Appointment lag time decreased by 4.7days (95% CI 2.3 to 7.0days, P<0.001) from 14.1days to 9.4days in the new patient group. More new patients were seen within 1week compared to baseline (50.6% versus 19.1%; P<0.0001). The mean number of new patient visits per month increased from 158.5 to 225.0 (P=0.0004). The cancellation rate and appointment lag times did not decrease for established patient visits, as expected because open-access scheduling was not implemented for this group. CONCLUSIONS: Access to care for new chronic pain patients improved with modified open-access scheduling. However, their mean cancellation rate only decreased from 35.7% to 31.5%, making this a marginally effective strategy to reduce cancellations.

Bulbar conjunctival microvascular responses in dry eye.

PURPOSE: Conjunctival microvascular responses may be a surrogate metric of efferent neural pathway function innervating the ocular surface as changes in blood flow occur within seconds after a stimulus. As somatosensory dysfunction may partially underlie dry eye (DE), in this study we evaluate whether bulbar conjunctival microvascular alterations correlate with various aspects of DE. METHODS: Fifty-six DE patients were prospectively recruited from a Veterans Affairs ophthalmology clinic over an 11-month period. DE symptoms and ocular pain were assessed along with DE signs. A novel functional slit lamp biomicroscope (FSLB) was used to image the temporal bulbar conjunctiva from the right eye before and after central corneal stimulation with an air puff. Blood flow velocities were measured and noninvasive microvascular perfusion maps (nMPMs) were created. RESULTS: The bulbar blood flow velocity was 0.50 ± 0.15 mm/s at baseline and increased to 0.55 ± 0.17 mm/s after stimulation (P < 0.001); the average change in velocity was 0.05 ± 0.09. nMPMs values and venule diameter, on the other hand, did not significantly increase after stimulation (1.64 ± 0.004 at baseline, 1.65 ± 0.04 after stimulation, P = 0.22 and 22.13 ± 1.84 µm at baseline, 22.21 ± 2.04 µm after stimulation, P = 0.73, respectively). Baseline blood flow velocity positively associated with Schirmer scores (r = 0.40, P = 0.002). Those with higher self-rated wind hyperalgesia demonstrated less change in blood flow velocity (r = -0.268, P = 0.046) after air stimulation on the central cornea. CONCLUSION: Conjunctival blood flow velocity, but not vessel diameter or complexity, increases after wind stimuli. Baseline flow positively correlated with Schirmer scores while change in flow negatively correlated with self-reported wind hyperalgesia.

Characteristics of Ocular Pain Complaints in Patients With Idiopathic Dry Eye Symptoms.

OBJECTIVE: The purpose of this study was to examine the severity and quality of ocular pain complaints in patients with dry eye symptoms. METHODS: Subjects with clinically relevant dry eye symptoms (dryness, discomfort, tearing) of unknown origin seen in the Miami Veterans Affairs eye clinic were administered questionnaires for dry eye symptoms and ocular pain and underwent a standardized ocular examination. Qualities and severity ratings of ocular pain in subjects with idiopathic dry eye were compared with similar measures from published data in other chronic pain populations. RESULTS: The study sample consisted of 154 subjects, of which 91% were men and ranged in age from 27 to 89 (mean age=61). Fifty-three percent of participants reported an average ocular pain of at least moderate intensity (numerical rating scale≥4), with specific characteristics (i.e., "burning" spontaneous pain) reported at frequencies comparable to prevalent chronic neuropathic pain syndromes as reported in the literature. Significant correlations were found between ocular pain metrics and dry eye symptom severity scores (r=0.57-0.66). Dry eye signs, however, did not generally correlate with ocular pain severity. CONCLUSIONS: A significant proportion of subjects with idiopathic dry eye symptoms reported moderate or greater ocular pain intensity, with most endorsing descriptors commonly used by patients with nonocular neuropathic pain conditions. Identifying subgroups of dry eye patients based on the presence and characteristics of ocular pain complaints may improve dry eye subclassification and better individualize treatment strategies.

Longitudinal Examination of Frequency of and Risk Factors for Severe Dry Eye Symptoms in US Veterans.

Importance: Dry eye syndrome is a common condition that affects millions of individuals. Many cross-sectional studies have evaluated risk factors for dry eye severity, but few have assessed risk factors or symptom progression over time. Objectives: To assess symptom progression in dry eye syndrome and determine risk factors associated with severe symptoms at 1 year. Design, Setting, and Participants: A longitudinal study was conducted from October 1, 2013, to April 30, 2015, among patients at the Miami Veterans Affairs Hospital with a wide variety of dry eye symptoms and signs (ranging from none to severe). Main Outcomes and Measures: Change in dry eye symptom severity during 1 year, as assessed by responses to dry eye symptom questionnaires administered at the initial visit and 1 year later, as well as baseline risk factor analysis for severe dry eye symptoms at 1 year, defined as a Dry Eye Questionnaire 5 score of 12 or more. Results: Of the 120 patients (mean [SD] age, 64 [11] years; 109 male and 11 female), 26 of 58 (44.8%) with either no symptoms or mild or moderate symptoms at baseline progressed to more severe symptoms at 1 year, while 46 of 62 patients (74.2%) with severe symptoms at baseline reported that severe symptoms persisted at 1 year. Baseline ocular risk factors for severe dry eye symptoms at 1 year included more severe dry eye symptoms, ocular pain, and neuropathic pain-like ocular symptoms. Nonocular risk factors included sleep disturbances (eg, sleep apnea and insomnia), mental health status (eg, posttraumatic stress disorder and depression), nonocular pain, and medications (eg, anxiolytics and analgesics). In a multivariable analysis, the most significant risk factors were sleep apnea (odds ratio [OR], 3.80; 95% CI, 1.00-14.49; P = .05), Dry Eye Questionnaire 5 score (OR, 1.15; 95% CI, 1.02-1.30; P = .02), and posttraumatic stress disorder score (OR, 1.04; 95% CI, 1.01-1.08; P = .02). Conclusions and Relevance: Patients with severe dry eye symptoms and ocular pain at baseline were more likely to have persistent severe dry eye symptoms on 1-year follow-up. Furthermore, nonocular risk factors that have been associated with dry eye cross-sectionally, such as psychiatric comorbidities and nonocular pain, were also associated with severe dry eye symptoms at 1 year. Although this cohort was limited to US veterans, which may not be generalizable to other populations, our results suggest that pain perception and severity are important when evaluating and managing dry eye.

Evidence that dry eye is a comorbid pain condition in a U.S. veteran population.

INTRODUCTION: Recent evidence suggests that dry eye (DE) may be comorbid with other chronic pain conditions. OBJECTIVES: To evaluate DE as a comorbid condition in the U.S. veteran population. METHODS: Retrospective review of veterans seen in the Veterans Administration Healthcare System (Veteran Affairs) between January 1, 2010, and December 31, 2014. Dry eye and nonocular pain disorders were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. Dry eye was further separated into ICD-9 codes representing tear film dysfunction or ocular pain. χ2 and logistic regression analyses were used to examine frequency and risk of DE, ocular pain, and tear film dysfunction by pain disorders. RESULTS: Of 3,265,894 veterans, 959,881 had a DE diagnosis (29.4%). Dry eye frequency increased with the number of pain conditions reported (P < 0.0005). Ocular pain was most strongly associated with headache (odds ratio [OR] 2.98; 95% confidence interval [CI] 2.95-3.01), tension headache (OR 2.64; 95% CI 2.58-2.71), migraine (OR 2.58; 95% CI 2.54-2.61), temporomandibular joint dysfunction (OR 2.39; 95% CI 2.34-2.44), pelvic pain (OR 2.30; 95% CI 2.24-2.37), central pain syndrome (OR 2.24; 95% CI 1.94-2.60), and fibromyalgia/muscle pain (OR 2.23; 95% CI 2.20-2.26), all P < 0.0005. Tear film dysfunction was most closely associated with osteoarthritis (OR 1.97; 95% CI 1.96-1.98) and postherpetic neuralgia (OR 1.95; 95% CI 1.90-2.00), both P < 0.0005. CONCLUSIONS: Dry eye, including both ocular pain and tear film dysfunction, is comorbid with pain conditions in this nationwide population, implying common mechanisms.