Allison L. McClellan

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms.

Purpose To examine associations between corneal mechanical thresholds and metrics of dry eye. Methods This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. Results A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearmans ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = −0.13 to −0.27, P < 0.05 for values between −0.18 and −0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = −0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Conclusions Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints.

Dry Eye Profiles in Patients with a Positive Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test Versus Negative Patients

PURPOSE To compare dry eye (DE) symptoms and signs in subjects who tested positive versus those who tested negative for ocular surface matrix metalloproteinase 9 (MMP-9) using the InflammaDry point-of-care test (RPS, Sarasota, FL). METHODS In this cross-sectional study, individuals seen in the Miami Veterans Affairs eye clinic with DE symptoms, as evidenced by DE questionnaire 5 (DEQ5) ≥6, were given standardized questionnaires to assess DE symptoms and ocular and non-ocular pain complaints. Also, a complete evaluation was conducted to measure ocular surface signs of DE. MMP-9 testing was performed using the InflammaDry once in each eye, per the manufacturers instructions. The main outcome measure was a comparison of DE symptoms and signs in MMP-9 positive versus negative subjects. RESULTS Of 128 subjects, 50 (39%) were positive for MMP-9 for InflammaDry testing in either eye. No statistically significant differences in mental health indices, DE symptoms, or ocular surface signs were seen in subjects based on MMP-9 status. CONCLUSION In our population, there was no difference in the DE profile by both symptoms and signs between those testing positive versus negative for MMP-9 on the ocular surface. This suggests that clinical exam alone cannot predict patients with clinically significant inflammation.

The impact of conjunctivochalasis on dry eye symptoms and signs.

PURPOSE The purpose of this project was to study the relationship between conjunctivochalasis (Cch) and ocular signs and symptoms of dry eye. METHODS Ninety-six patients with normal eyelid and corneal anatomy were prospectively recruited from a Veterans Administration hospital over 12 months. Symptoms (via the dry eye questionnaire 5 [DEQ5]) and signs of dry eye were assessed along with quality of life implications. Statistical analyses comparing the above metrics among the three groups included χ(2), analysis of variance, and linear regression tests. RESULTS Participants were classified into three groups: nasal conjunctivochalasis (NCch; n = 31); nonnasal conjunctivochalasis (non-NCch; n = 41); and no conjunctivochalasis (no-Cch; n = 24). Patients with NCch had more dry eye symptoms than those with non-NCch (DEQ5: NCch = 13.8 ± 5.0, non-NCch = 10.2 ± 5.0, no-Cch = 11.6 ± 5.8; P = 0.014), and more ocular pain than those with Non-NCch and no-Cch (numerical rating scale [NRS]: NCch = 4.5 ± 3.0, non-NCch = 2.3 ± 2.8, no-Cch = 3.3 ± 2.6; P = 0.008). They also had worse dry eye signs compared to those with no-Cch measured by Schirmer score with anesthesia (NCch = 14.5 ± 6.9, non-NCch = 16.8 ± 8.2, no-Cch = 19.9 ± 6.4; P = 0.039); meibomian gland dropout (NCch 1.8 ± 0.9, non-NCch = 1.4 ± 1.0, no-Cch = 1.0 ± 1.0; P = 0.020); and eyelid vascularity (NCch = 0.84 ± 0.8, non-NCch = 0.74 ± 0.7, no-Cch = 0.33 ± 0.6; P = 0.019). Moreover, those with NCch more frequently reported that dry eye symptoms moderately to severely impacted their quality of life (NCch = 87%, non-NCch = 51%, no-Cch = 58%; P = 0.005). CONCLUSIONS The presence of NCch associates with dry eye symptoms, abnormal tear parameters, and impacts quality of life compared with non-NCch and no-Cch. Based on these data, it is important for clinicians to look for Cch in patients with symptoms of dry eye.

ω-3 tear film lipids correlate with clinical measures of dry eye

Purpose ω-3 and ω-6 polyunsaturated fatty acids modulate inflammatory processes throughout the body through distinct classes of lipid mediators that possess both proinflammatory and proresolving properties. The purpose of this cross-sectional study was to explore the relationship between lipid profiles in human tears and dry eye (DE) symptoms and signs. Methods Forty-one patients with normal eyelid and corneal anatomy were prospectively recruited from a Veterans Administration Hospital over 18 months. Symptoms and signs of DE were assessed, and tear samples was analyzed by mass spectrometry–based lipidomics. Statistical analyses comparing the relationship between tear film lipids and DE included Pearson/Spearman correlations and t-tests. Results Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were present in more than 90% of tear film samples. The ratio of ω-6 (AA) to ω-3 (DHA+EPA) fatty acids was correlated with multiple measures of tear film dysfunction (tear breakup time, Schirmer 2 scores, and corneal staining; all P < 0.05). Arachidonic acid–derived prostaglandin E2 was detected in the majority of samples and correlated with low tear osmolarity, meibomian gland plugging, and corneal staining. Conclusions Both ω-3 and ω-6 lipid circuits are activated in the human tear film. The ratio of ω-6:ω-3 tear lipids is elevated in DE patients in proportion to the degree of tear film dysfunction and corneal staining. Metabolic deficiency of ω-3 tear film lipids may be a driver of chronic ocular surface inflammation in DE.

Ocular inflammation in the setting of concomitant systemic autoimmune conditions in an older male population

Purpose: This retrospective cross-sectional study was designed to investigate the frequency and types of inflammatory ocular manifestations of specific systemic autoimmune diseases in a South Florida Veterans Affairs Hospital population. Methods: Demographic and medical diagnosis information was extracted from the Veterans Administration database for 1225 patients. These patients were seen in Miami and Broward Veterans Affairs hospitals between April 18, 2008, and April 17, 2013, and were diagnosed with at least 1 of the following: systemic lupus erythematosus, sarcoid, rheumatoid arthritis, polymyalgia rheumatica, Takayasu arteritis, giant cell arteritis, Kawasaki disease, polyarteritis nodosa, Buerger disease, Henoch–Schonlein purpura, Behcet syndrome, granulomatosis with polyangiitis, other polyarteritis nodosa–associated vasculitides, or arteritis not otherwise specified. Results: Of 1225 patients, 618 were seen in the VA eye clinic and 25 were diagnosed with concomitant inflammatory ocular conditions. Uveitis was the most common, and included 8 cases of anterior, 1 anterior–intermediate, 1 intermediate, 2 panuveitis, and 3 unspecified. Other manifestations included 7 cases of keratitis and 2 each of scleritis, episcleritis, and acute ischemic optic neuropathy. The overall frequency of inflammatory ocular disease was 2%. The diseases associated with the highest frequency of ocular involvement were granulomatosis with polyangiitis (1/8), sarcoid (9/198), giant cell arteritis (2/68), and rheumatoid arthritis (11/576). Of these 25 patients, 9 were diagnosed with eye disease before systemic disease. Conclusions: In this population, ocular manifestations were rarely the presenting feature of systemic disease, but autoimmune disorders are an important underlying cause of inflammatory eye disease that should be considered on first evaluation, even in this “nontraditional,” predominantly male, autoimmune disease population.

Epidemiology of Meibomian Gland Dysfunction in an Elderly Population

Purpose: To study the epidemiology of meibomian gland (MG) dysfunction in an elderly, predominantly male population. Methods: Prospective study of 233 subjects seen in the Miami Veterans Affairs eye clinic. Patients underwent a complete ocular surface examination, including dry eye questionnaires and tear assessments (osmolarity, tear breakup time, corneal staining, Schirmer test). The main outcome measures were correlations between MG parameters and demographics, dry eye symptoms, and tear parameters. The studied MG parameters were eyelid vascularity and meibum quality; a score ≥2 for either parameter was considered abnormal. Results: Mean age of the 233 subjects was 63 years (SD = 11); 91% were male and 59% had at least 1 abnormal MG parameter (abnormal quality 55%; vascularity 17%). Demographically, patients with abnormal MG parameters were significantly older than their counterparts without these findings. Whites were more likely to have abnormal eyelid vascularity compared with blacks [n = 36 (31%) vs. n = 1 (1%), P < 0.0005] but no differences were noted between races with respect to meibum quality. Abnormal meibum quality, but not abnormal vascularity, was significantly associated with more severe dry eye symptoms. Similarly, abnormal meibum quality, but not eyelid vascularity, was significantly associated with worse dry eye signs, including decreased tear breakup time and increased corneal staining (P < 0.05 for all). Conclusions: MG dysfunction is a frequent finding in an elderly, predominantly male population with racial differences noted in the frequency of abnormal eyelid vascularity but not in MG quality. Abnormal meibum quality was significantly associated with more severe dry eye symptoms and signs.

Evidence of central sensitisation in those with dry eye symptoms and neuropathic-like ocular pain complaints: incomplete response to topical anaesthesia and generalised heightened sensitivity to evoked pain

Objective To evaluate how closely neuropathic-like ocular pain (NOP) symptoms align with a metric of central sensitisation (ie, the presence of persistent ocular pain after topical anaesthetic placement) in individuals with dry eye (DE) symptoms. Design Cross-sectional study of 224 individuals with DE symptoms seen in the Miami Veterans Affairs eye clinic. An evaluation was performed consisting of questionnaires regarding DE symptoms, NOP descriptors and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Subsequent analyses were performed to examine for differences between those with and without ocular pain after topical anaesthetic placement. Results The mean age was 62 years with 91% being men. DE symptoms and NOP symptoms were higher in subjects with persistent ocular pain after anaesthesia. Most DE signs were not related to persistent pain, with the exception of meibum quality. Individuals with persistent ocular pain also demonstrated greater sensitivity to evoked pain at testing sites on the forehead and forearm. When examining receiver operator characteristic curves considering persistent pain as a gold standard for central sensitisation within the corneal pathway, intensity of ocular pain ratings, Ocular Surface Disease Index scores and sensitivity to light provided the most robust relationships, each with an area under the curve of 0.72. Conclusions Individuals with DE symptoms and persistent ocular pain after topical proparacaine (a marker of central sensitisation to pain) more frequently report NOP-like symptoms and demonstrate increased sensitivity to evoked pain.

Epidemiology of Ocular Surface Squamous Neoplasia in a Veterans Affairs Population.

Purpose: To evaluate the epidemiology of ocular surface squamous neoplasia (OSSN) and its associated risk factors in a South Florida Veterans Affairs Hospital population. Methods: Retrospective case–control study. Twenty-eight confirmed cases of OSSN from 24,179 veterans who received care at the Miami Veterans Affairs Healthcare System and affiliated satellite eye clinics between March 1, 2007, and March 1, 2012. Data extracted from the veterans administration database that comprised demographic information and medical diagnosis information [based on International Classification of Disease (ICD-9) codes]. The main outcome measures were the period prevalence of OSSN and identification of factors associated with the presence of disease. Results: The period prevalence of OSSN in our population was 0.1%. The risk factors studied included UV-related dermatologic diseases (melanoma, squamous and basal cell cancer, and actinic keratosis), UV-related ocular conditions (pterygium), HIV seropositivity, human papilloma virus–related diseases, and tobacco use. The presence of skin malignancy (squamous cell carcinoma and/or basal cell carcinoma) and pterygium was found to be significantly associated with the presence of OSSN [odds ratio, 4.40; 95% confidence interval, 2.03–9.55; P < 0.0005 and odds ratio, 16.2; 95% confidence interval, 7.11–36.9; P < 0.0005, respectively]. Conclusions: The presence of neoplasias and ocular conditions related to sun exposure was the most important risk factor for the occurrence of OSSN in a South Florida Veterans Affairs Healthcare System population consistent with previous epidemiological reports worldwide.

Impact of Eyelid Laxity on Symptoms and Signs of Dry Eye Disease.

Purpose: To study the relationship between eyelid laxity and ocular symptoms and signs of dry eye (DE). Methods: A total of 138 patients with normal external anatomy were prospectively recruited from a Veterans Administration hospital. Symptoms (via the Dry Eye Questionnaire 5 and Ocular Surface Disease Index) and signs of DE were assessed along with presence or absence of eyelid laxity. Results: It was observed that 71% of participants (n = 98) had clinical evidence of eyelid laxity (upper and/or lower) compared with 29% (n = 40) with no eyelid laxity. Individuals with eyelid laxity were older (67 ± 10 vs. 55 ± 8 years without laxity, P < 0.005) and more frequently male (76% of males had laxity vs. 18% females, P < 0.005). Patients with eyelid laxity had increased symptoms and signs of DE compared with their counterparts without laxity including ocular pain described as grittiness (63% vs. 45%, P = 0.049), decreased tear break-up time (8.6 ± 3 vs. 10.3 ± 4 seconds, P = 0.02), increased corneal staining (2.5 ± 3 vs. 1 ± 2, P = 0.002), decreased Schirmer score (14±6 vs. 17±7 mm, P = 0.01), increased meibomian gland drop out (2 ± 1 vs. 0.8 ± 0.8, P < 0.005), increased eyelid vascularity (0.8 ± 0.8 vs. 0.2 ± 0.5, P < 0.005), and more abnormal meibum quality (2 ± 1.3 vs. 1.4 ± 1.2, P = 0.02). In a multivariable analysis considering both signs of DE and laxity, lower eyelid laxity remained significantly associated with ocular surface disease index scores, suggesting a direct effect of laxity on symptoms of DE. Conclusions: The presence of eyelid laxity associates with abnormal tear parameters compared with the absence of eyelid laxity. Based on these data, it is important for clinicians to test for eyelid laxity in patients with symptoms and/or signs of DE.

Human Tear Serotonin Levels Correlate with Symptoms and Signs of Dry Eye

PURPOSE Serotonin, a neurotransmitter known to be involved in nociceptor sensitization, is present in human tears. The purpose of this study was to correlate tear serotonin levels, as a marker of nociceptor sensitization, to facets of dry eye (DE), including symptoms and signs. DESIGN Cross-sectional study. PARTICIPANTS A total of 62 patients with normal eyelid and corneal anatomy were prospectively recruited from a Veterans Administration Ophthalmology Clinic over 11 months. METHODS Dry eye symptoms (Ocular Surface Disease Index [OSDI]), signs (tear break-up time [TBUT], corneal staining, and Schirmers score), and clinical descriptors of neuropathic ocular pain (NOP) (sensitivity to light or sensitivity to wind) were assessed. For tear analysis, each patients tears were collected after instilling 50 μl of sterile saline to the lower cul-de-sac of each eye and using capillary action microcaps to collect the ocular wash. Tear serotonin levels were measured using enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES Correlations between tear serotonin concentrations and DE symptoms and signs. RESULTS The mean age of the population was 61±14 years, and 84% (n = 52) of the patients were male. Serotonin concentrations negatively correlated with Schirmers scores (r = -0.28; P = 0.02) but did not correlate with other DE parameters, such as OSDI scores, sensitivity to light or wind, TBUT, and staining. According to our hypothesis, we divided patients into groups based on both DE symptoms and aqueous tear production; serotonin concentrations were significantly higher in DE group 1 (OSDI ≥6 and Schirmers <8) compared with both DE group 2 (OSDI ≥6 and Schirmers ≥8) and controls (OSDI <6 and Schirmers ≥8). Patients in DE group 2 more frequently reported sensitivity to light (64%) and wind (67%) compared with DE group 1 (40% and 60%, respectively) and controls (8% and 17%, respectively). CONCLUSIONS Patients with DE symptoms and aqueous tear deficiency had higher tear serotonin levels compared with those with DE symptoms but normal tear production and those without DE symptoms.