The spectrum of allergic ocular diseases.

OBJECTIVE: The purpose of this article is to review the pathophysiologic mechanisms, differential diagnosis, evaluation, and treatment of the various manifestations of ocular allergy, with an especial focus on immunoglobulin E (IgE)-mediated disease. DATA SOURCES: A PubMed search was performed to include articles, using the search terms ocular allergy and allergic conjunctivitis. STUDY SELECTIONS: Recent and relevant human studies in the English language pertaining to our topic of study were selected. Animal studies pertaining to pathophysiology of ocular allergy were also reviewed. We focused on clinical trials, practice guidelines, reviews, and systematic reviews. In addition, case reports were reviewed if they described rare clinical presentations, disease mechanisms, or novel therapies. RESULTS: Ocular allergy encompasses both IgE- and non-IgE-mediated disease, and the clinical severity may range from mild to sight-threatening inflammation. A comprehensive treatment regimen including education, lifestyle measures, topical therapies, and even systemic interventions may be necessary for the effective management of ocular allergies, tailored according to symptom severity. CONCLUSION: Ocular allergy is frequently encountered by allergists and eye-care specialists, and despite progressively increasing incidence, it often remains underdiagnosed and, hence, untreated.

Associations Between Systemic Omega-3 Fatty Acid Levels With Moderate-to-Severe Dry Eye Disease Signs and Symptoms at Baseline in the Dry Eye Assessment and Management Study.

PURPOSE: Omega-3 (n-3) fatty acid supplementation is used to treat systemic inflammatory diseases, but the role of n-3 in the pathophysiology and therapy of dry eye disease (DED) is not definitive. We evaluated the relationship of systemic n-3 levels with signs and symptoms at baseline in the Dry Eye Assessment and Management (DREAM) Study. METHODS: Blood samples from participants at baseline were analyzed for n-3 and n-6, measured as relative percentage by weight among all fatty acids in erythrocytes. Symptoms were evaluated using the Ocular Surface Disease Index. Signs including conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmer's test with anesthesia were also evaluated. RESULTS: There was no correlation between the systemic n-3 levels and DED symptoms. When the associations with signs of DED were assessed, lower DHA levels were associated with higher conjunctival staining, with mean scores of 3.31, 2.96, and 2.82 for low, medium, and high levels of DHA, respectively (linear trend P=0.007). None of the other signs were associated with DHA or the other measures of n-3. CONCLUSION: Previous studies have found varying results on the role of n-3 supplementation with the signs and symptoms of DED. Among patients with DED enrolled in the DREAM Study, lower systemic n-3 levels were not associated with worse symptoms and most signs of DED.

Omegas and Dry Eye: More Knowledge, More Questions.

The omega-3 (ω3) and omega-6 (ω6) essential fatty acid knowledge base has been exploding. In the last 5 years, at least 12 clinical trials on ω3 and ω6 supplementation and dry eye disease (DED) were published in the peer-reviewed literature (2010 to 2015), about double the amount published in the 5 years prior. Although there is increasing scientific evidence that supports the potential use of ω3 and ω6 supplementation for DED, there are limited randomized controlled trials to properly inform evidence-based medicine. Dry eye disease is one of the most common eye conditions that patients seek care for and cannot be disregarded as a trivial condition. The roles of ω3 and ω6 polyunsaturated fatty acids (PUFAs) in the treatment of DED are still not completely understood. There are distinct and sometimes opposite effects of ω3 and ω6 PUFAs, both of which are essential and cannot be synthesized de novo in the body. These fatty acids must be obtained from the diet, which varies widely by region, even within the United States. Omega-3 PUFAs have anti-inflammatory effects; a proper ratio of ω6:ω3 in the diet must be established. Objectively correlating changes in dry eye syndrome with blood levels of ω3 PUFAs has not been done in a large-scale multisite study. Just as Wilder's law of initial value states that "the direction of response of a body function to any agent depends to a large degree on the initial level of that function," the baseline status needs to be taken into account. There is also no consensus on the dose, composition, length of treatment, and so on with ω3 or ω6 PUFAs. Increased quality evidence on the usefulness of over-the-counter supplements is needed to enable eye care providers to confidently outline specific treatment recommendations for using ω3 PUFAs in DED.

Pilocarpine HCl 1.25% for treatment of presbyopia after laser vision correction: pooled analysis of two phase 3 randomized trials (GEMINI 1 and 2).

PURPOSE: To evaluate the efficacy of topical pilocarpine HCl 1.25% (Pilo) in treating presbyopia in individuals with or without a history of laser vision correction (laser-assisted in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]). SETTING: Multiple clinical sites. DESIGN: Pooled analysis of 2 identically designed prospective, randomized, vehicle-controlled studies (GEMINI 1 and 2). METHODS: Adults aged 40 to 55 years with presbyopia received once-daily Pilo or vehicle bilaterally for 30 days. Responder rates for ≥3-line improvement in mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) were determined on day 30. RESULTS: Among participants with a history of LASIK/PRK (n = 39 in the Pilo group, n = 41 in the vehicle group), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.7%, 38.9%, 41.7%, 37.8%, 16.2%, 13.9%, and 8.3% with Pilo and 0.0%, 2.6%, 10.5%, 5.1%, 7.7%, 2.6%, and 0.0% with vehicle. Responder rates in the LASIK/PRK subgroup were significantly higher with Pilo than vehicle at hours 0.25 ( P = .0087), 0.5 ( P = .0001), 1 ( P = .0022), and 3 ( P = .0005). In contrast, there were no significant differences in responder rates between Pilo-treated participants with and without LASIK/PRK. Among non-LASIK/PRK participants in the Pilo group (n = 336), responder rates for ≥3-line improvement in DCNVA on day 30 at hours 0.25, 0.5, 1, 3, 6, 8, and 10, respectively, were 16.8%, 32.7%, 39.0%, 28.0%, 17.4%, 12.6%, and 10.5%. CONCLUSIONS: Pilo treatment effectively and similarly improved DCNVA in presbyopes with or without a history of laser vision correction.

Demodex.

PURPOSE: Demodex folliculorum and Demodex brevis are ectoparasites with an astounding prevalence of 100% in patients aged 70 years and older. Every person in this age group is estimated to carry a colony of 1000 to 2000 mites. With such a high prevalence, little attention has been paid to the mite among eye care practitioners. We demonstrate a clinical sequence in a set of case reports to identify the mite. The clinical sequence includes a clinical history of blepharitis, dry eyes, and/or ocular allergy; slit lamp examination of cylindrical dandruff; and confirmation using light microscope evaluation of epilated lashes. CASE REPORTS: Patient 1 was a 68-year-old woman who demonstrates associations with dry eyes and diabetes. Patient 2 was a 44-year-old man with uncommonly seen D. brevis present. Patient 3 was a 40-year-old woman with dry eyes and allergy, showing mite tails protruding from base of lashes. Patient 4 was a 60-year-old woman who demonstrates the association with rosacea. Patient 5 was a 53-year-old woman intermittently taking topical steroid and antibiotic combination medications, with an actual mite photographed on the surface. CONCLUSIONS: Following a clinical sequence helps identify Demodex, the underdiagnosed, undertreated, and underappreciated ocular surface disease.

Allergic conjunctivitis and dry eye syndrome.

BACKGROUND: Allergic conjunctivitis (AC) and dry eye syndrome (DES) are 2 of the most common anterior inflammatory disorders of the ocular surface and one does not preclude the coexistence of the other. OBJECTIVES: To examine the potential overlap between AC and DES as comorbidities. METHODS: Using the validated questionnaire known as Subjective Evaluation of Symptom of Dryness, we studied self-reported itchiness, dryness, and redness. In an outpatient optometric setting, 689 patients treated from January 1, 2007, to January 1, 2011, were surveyed for their ocular history and categorized according to their reported level of discomfort of itchiness, dryness, and redness. RESULTS: Patients ranged in age from 5 to 90 years (median age, 25 years; 39.5% male; 60.5% female). In the studied 689 patients, clinically significant itchiness was found in 194 (28.2%), dry eyes in 247 (35.8%), and redness in 194 (28.2%). Symptom overlap was demonstrated in many of the patients. Of the 194 patients with itchiness, 112 (57.7%) had clinically significant dryness. In the 247 patients with dry eyes, 112 (45.3%) had clinically significant itch. Redness was apparent in 120 of the 194 patients with itch (61.9%) and 122 of the 247 patients with dryness (49.4%). Statistical analysis demonstrated that self-reported itchiness, dryness, and redness were not independent of each other (P<.001; Pearson χ(2) test). The odds of patients with "itchy eyes" also experiencing dry eyes were 2.11 times and the odds of these patients also experiencing redness were 7.34 times that of patients with nonitchy eyes. CONCLUSIONS: Most patients with "itchy eyes" consistent with AC also have dry eyes and redness. These results suggest that some symptomatic patients concomitantly have features of AC and DES.

An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial.

PURPOSE: To evaluate the efficacy and safety of a nano-emulsion artificial tear (OM3) containing carboxymethylcellulose (CMC) and glycerin, flaxseed oil and castor oil, and three osmoprotectants (levocarnitine, erythritol, and trehalose) compared with an artificial tear (Refresh Optive Advanced [ROA]) containing the same ingredients with the exception of trehalose and flaxseed oil. METHODS: In this multicenter, double-masked, randomized, two-arm, parallel-group, 6-visit study (screening, baseline, and days 7, 30, 60, and 90), subjects with dry eye disease underwent an open-label, 7-day run-in with CMC 0.5% (Refresh Plus), before 1:1 randomization to OM3 or ROA for 90 days (both instilled ≥2 daily). Ocular Surface Disease Index (OSDI; primary endpoint change from baseline at day 90), tear film breakup time (TBUT), and ocular staining (combined/corneal/conjunctival) were assessed; change from baseline in these parameters was calculated at each timepoint. Treatment-related adverse events (AEs) were assessed at each visit. RESULTS: Overall, 242 subjects were randomized (OM3, n = 120; ROA, n = 122). At day 90, significant improvements in OSDI, ocular staining and TBUT were evident in both treatment groups. Significant (P < 0.05) between-group differences in favor of OM3 were observed for combined ocular staining (all timepoints), corneal staining (day 90), and conjunctival staining (day 30). Treatment-related AEs were higher in the ROA (9.8%) versus OM3 (6.7%) group; blurred vision was among the most commonly reported AE (OM3 0% vs ROA 4.1%). CONCLUSION: These findings support the application of OM3, a novel preservative-free, nano-emulsion tear formulation with trehalose and flaxseed oil, for the treatment of dry eye disease.

The anatomical and functional relationship between allergic conjunctivitis and allergic rhinitis.

There are numerous anatomic connections between the allergic conjunctivitis and allergic rhinitis. The most obvious reason is the physical connection via the nasolacrimal apparatus. However, a closer look at innervation, circulatory, lymphatic, and neurogenic systems reveals much more than a physical connection. The eye is richly innervated by parasympathetic nerves that enter the eyes after traveling in conjunction with the parasympathetic input to the nasal cavity. Parasympathetic innervation governing the tear film and nasal secretion can intersect at the pterygopalatine ganglion. Neurogenic inflammation affects both the eye and the nose as evidenced by the presence of the same neurogenic factors. Venous flow is in the SOV area connecting the eye and the nose, once thought to be without valves. In the past, this thinking is the basis for concern about the danger triangle of the face. Recent literature has shown otherwise. Although valves are present, there are still pathways where bidirectional flow exists and a venous connection is made. The most likely area for venous communication is the pterygoid plexus and cavernous sinus. The venous flow and connections also offers a pathway for allergic shiners. Understanding the mutual connections between the nasal mucosa and the ocular surface can also affect treatment strategies.

Prelens tear stability: relationship to symptoms of dryness.

BACKGROUND: Prelens tear thinning time (PLTTT) was used to quantify tear stability relative to symptoms of dryness. METHODS: Twenty-two subjects were measured for PLTTT in this investigator-masked study. Specular reflection was performed, and the timed appearance of a colored interference fringe within the reflection under high magnification indicated PLTTT. Two symptom questionnaires were given: subjective evaluation of symptom of dryness (SESoD) and Ocular Surface Disease Index (OSDI). RESULTS: The median PLTTT was 3.9 seconds for asymptomatic lens wearers. For those with dryness, the median PLTTT was 2.2 seconds. For SESoD, 69% of asymptomatic subjects had an average PLTTT of 3.0 seconds or greater. Eighty-three percent of symptomatic subjects had an average PLTTT of less than 3.0 seconds (P = 0.03). For OSDI, 71% of asymptomatic subjects had an average PLTTT of 3.0 seconds or greater. Seventy-five percent of symptomatic subjects had an average PLTTT of <3.0 seconds (P = 0.04). CONCLUSIONS: The data suggest that a PLTTT breakup time of <3.0 seconds might be suitable criterion for tear film dysfunction causing dryness symptoms. PLTTT may be a rapid and useful clinical method for practitioners to provide a glimpse of self-reported symptoms caused by contact lens-related dryness.

Use of cyclosporine 0.05% ophthalmic emulsion for contact lens-intolerant patients.

PURPOSE: To evaluate the effect of cyclosporine 0.05% ophthalmic emulsion (Restasis, Allergan, Inc., Irvine, CA) on contact lens comfort and reducing dry eye symptoms in patients with contact lens intolerance. METHODS: A 5-week, randomized, investigator-masked study of 17 patients with self-reported contact lens-related dryness. Patients were randomized to cyclosporine twice per day or rewetting drops (carboxymethylcellulose 0.5%, Refresh Contacts) twice per day, to be used before and after lens wear. Changes from baseline in fluorescein staining of the cornea and conjunctiva and in tear breakup time were used to determine improvement of dry eye signs. Symptoms were assessed by lens wear time, use of rewetting drops during lens wear, subjective evaluation of dryness, and the completion of the Ocular Surface Disease Index questionnaire. RESULTS: Five weeks of cyclosporine treatment significantly improved dry eye symptoms (mean improvement of 0.88 +/- 0.64 with cyclosporine; no change of 0 +/- 0.58 [P = 0.01] with rewetting drops). Patients using cyclosporine decreased the use of rewetting drops by a mean 1.0 +/- 1.1 drops per day, and patients using rewetting drops increased their use (mean increase of 0.86 +/- 1.1 drops per day [P = 0.032]). Wearing time increased 1.9 +/- 2.1 hours per day with cyclosporine and 0.93 +/- 1.0 hours per day with rewetting drops (P = 0.258). There were no significant differences in mean corneal staining between groups. After 5 weeks, patients using cyclosporine showed statistically better improvements in temporal bulbar conjunctival fluorescein staining (decrease of 0.63 +/- 0.52 vs. increase of 0.57 +/- 0.67 [P = 0.002]) than patients using rewetting drops. Both treatments were tolerated well. CONCLUSIONS: The results of this pilot study indicate that cyclosporine 0.05% is beneficial for contact lens wearers with dry eye and reduces contact lens intolerance.