Patient perspectives on dry eye disease and chronic ocular surface pain: Insights from a virtual community-moderated dialogue.

PURPOSE: To understand patients' perspectives on living with dry eye disease (DED), and on the unmet needs in DED and chronic ocular surface pain (COSP) management. METHODS: A moderated, structured discussion with patients with ocular surface diseases and healthcare professionals (HCPs) was conducted using a virtual platform to capture patients' journey with DED, their opinion on unmet needs, and design and conduct of clinical trials in DED and COSP. RESULTS: Nine participants, including four patient representatives from patient organisations, one ophthalmologist and one optometrist participated in the discussion. Patients had DED of varying severity and aetiology; three patients had Sjögren's. Over 4 weeks, 785 posts were entered on the platform. Prior to diagnosis, patients rarely associated their symptoms with DED. Convenience and symptomatic relief scored higher than treating the disease. Patients expressed the need for plain language information and dialogue with knowledgeable and sensitive HCPs. Online forums and social media were suggested as key recruitment resources, whereas convenience and safety concerns were highlighted as main barriers to enrolment. The need for the inclusion of outcome measures that have a real impact on patients' experience of their condition was highlighted. Both target product profiles were received positively by participants, highlighting the twice-daily dosing regimen and convenience of the products. Participants acknowledged the value of digital tools and suggested the need to feel valued post-trial. CONCLUSIONS: This moderated dialogue provided actionable insights on the unmet needs in DED and useful inputs for consideration when designing future clinical trials for DED and COSP.

Understanding chronic ocular surface pain: An unmet need for targeted drug therapy.

Chronic ocular surface pain (COSP) may be defined as a feeling of pain, perceived as originating from the ocular surface, that persists for >3 months. COSP is a complex multifactorial condition associated with several risk factors that may significantly interfere with an individual's daily activities, resulting in poor quality of life (QoL). COSP is also likely to have a high burden on patients with substantial implications on global healthcare costs. While patients may use varied terminology to describe symptoms of COSP, any ocular surface damage in the ocular sensory apparatus (nociceptive, neuropathic, inflammatory, or combination thereof) resulting in low tear production, chronic inflammation, or nerve abnormalities (functional and/or morphological), is typically associated with COSP. Considering the heterogeneity of this condition, it is highly recommended that advanced multimodal diagnostic tools are utilized to help discern the nociceptive and neuropathic pain pathways in order to provide targeted treatment and effective clinical management. The current article provides an overview of COSP, including its multifactorial pathophysiology, etiology, prevalence, clinical presentation, impact on QoL, diagnosis, current management, and unmet medical needs.

Evaluation of an enhanced viscosity artificial tear for moderate to severe dry eye disease: A multicenter, double-masked, randomized 30-day study.

PURPOSE: In a randomized, controlled clinical trial, two lubricant artificial tear formulations with enhanced viscosity were compared: an investigational product at the time, containing carboxymethylcellulose 1.0% and glycerin 0.9% (CMC-GLY) with osmoprotectants, and a standard formula containing carboxymethylcellulose 1.0% alone (CMC). METHODS: This double-masked study recruited patients with moderate to severe dry eye at 10 US centers. After a 7-day run-in with CMC 0.5% (Refresh Tears) patients were randomized to use either CMC-GLY or CMC as needed, but at least 2 times daily for 30 days. Patients were stratified by Ocular Surface Disease Index© (OSDI) score into moderate (23-32) and severe (> 32-65) subgroups. Assessments included OSDI (primary efficacy variable), corneal and conjunctival staining, tear break-up time (TBUT), symptom surveys, and safety variables. Study visits were days 1 (baseline/randomization), 7, and 30. RESULTS: A total of 188 patients (94 CMC-GLY, 94 CMC) were enrolled. The severe subgroup had 67 CMC-GLY and 65 CMC patients. OSDI scores progressively improved and were similar at day 30 between treatment groups. At day 7, only the CMC-GLY group demonstrated significant improvements from baseline in OSDI score (all patients p < 0.001, severe p < 0.001), corneal staining (p = 0.004), and TBUT (p < 0.001). Between-group dose frequency for CMC-GLY was lower at day 7 (p = 0.031). Other efficacy results were similar between groups. The most commonly reported adverse event in both groups was blurred vision. CONCLUSIONS: Overall, the CMC-GLY artificial tear formulation was as effective as the CMC formulation. CMC-GLY demonstrated improvements at an earlier stage (day 7). Both artificial tear formulations were safe and well tolerated, with no treatment-related serious adverse events. These results support the use of the CMC-GLY artificial tear formulation as an effective treatment to reduce the symptoms and signs of dry eye disease.

Thickness mapping of the cornea and epithelium using optical coherence tomography.

PURPOSE: To measure corneal and epithelial thickness across four meridians using Optical Coherence Tomography (OCT) and to compare these measurements between normal non-lens wearers (NLW), rigid gas permeable (RGP) lens wearers, and RGP-wearing keratoconics (KC). METHODS: Both eyes of 60 subjects were measured (20 NLW, nine female:11 male, 27.6 +/- 5.9 years; 20 RGP, 20 female, 23.9 +/- 7.6 years; and 20 KC, seven female:13 male, 32.4 +/- 8.1 years). A customized fixation target employing LEDs in eight directions of gaze was attached to the OCT and corneal images obtained. Raw OCT scans were analyzed to yield values for corneal and epithelial thickness and color-coded maps were compiled. RESULTS: Central corneal thickness (CCT) was thinnest in KC (447 +/- 68 microm) and similar between RGP (518 +/- 32 microm; pKC < 0.001) and NLW (517 +/- 21 microm) (p(KC) < 0.001 NLW pRGP > 0.05). Peripheral corneal thickness in NLW was thickest in the superior temporal and thinnest in the inferior (I) regions (superior temporal(thickest) vs. I(thinnest) p < 0.001). Central epithelial thickness was thinnest in KC (44 +/- 7 microm), followed by RGP (50 +/- 4 microm), then NLW (54 +/- 2 microm) (pKC < 0.001 NLW p(RGP) < 0.05). Central epithelial thickness in the KC group was significantly thinner than in the RGP group (p < 0.001). In the NLW group, peripheral epithelial thickness was thicker (63 +/- 5 microm) than central (p < 0.001) and was thickest in the superior (S) region and thinnest in the inferior (I) region (S(thickest) vs. I(thinnest) p < 0.001). KC epithelium was thinnest in the inferior temporal meridian (42 +/- 5 microm). CONCLUSIONS: Thickness of the normal cornea and epithelium was greatest in the superior region. In all groups, the inferior cornea and epithelium was thinnest, and to a greater extent in the KC group.

Epithelial thickness changes from the induction of myopia with CRTH RGP contact lenses.

PURPOSE: To investigate changes in epithelial thickness after overnight wear of CRTH rigid gas-permeable (RGP) lenses (Paragon Vision Sciences, Mesa, AZ) for the correction of hyperopia. METHODS: Twenty subjects wore a +3.50 D hyperopia-correcting CRTH lens on one eye for a single night in an attempt to induce myopia (first study). The untreated eye served as the control. Corneal and epithelial thickness was measured at nine points across the horizontal meridian by OCT. Measurements were obtained the night before lens wear, immediately after lens removal the next morning, and 1, 3, 6, and 12 hours after removal. Measurements were obtained 28 hours later, to observe recovery. Then, the attempted hyperopic corrections of +1.50 and +3.50 D were evaluated, using CRTH lenses in both eyes of 20 subjects for a single night (second study). RESULTS: All values were compared to baseline unless otherwise stated. In the first study, the treated eye's central and midperipheral epithelial thickness increased by 21.5% +/- 8.6% and 13.3% +/- 7.6%, respectively, after lens removal (P < 0.001). The control eye's central epithelial thickness (CET) increased by 7.1% +/- 6.0% (P < 0.05). In the second study, CET increased by 17.6% +/- 8.5% (P < 0.001) in the +3.50 D-treated eye and by 13.3% +/- 4.8% (P < 0.001) in the +1.50 D-treated eye. Midperipheral epithelial thickening was 5.9% +/- 4.7% (P < 0.05) in the +3.50 D-treated eye and 6.0% +/- 6.3% (P < 0.05) in the +1.50 D-treated eye. CONCLUSIONS: CRTH lenses, designed to correct hyperopia, when worn overnight, caused an increase in CET. The amount of epithelial change seemed to differ with modified lens design.

Corneal refractive therapy with different lens materials, part 1: corneal, stromal, and epithelial thickness changes.

PURPOSE: To assess the corneal swelling response to two myopic correction corneal refractive therapy (CRT) lenses of varying Dk/t values, worn for a single night. Change in thickness of the total cornea, stroma, and epithelium was measured across the horizontal meridian using optical coherence tomography (OCT). METHODS: In this double-masked, randomized study, twenty subjects wore a CRT design lens in each eye, manufactured from Menicon Z (MenZ; Dk/t = 91) and Equalens II (EqII; Dk/t = 47) materials. Baseline corneal thickness was measured centrally and at four points either side of the central cornea using OCT, the night before sleeping at the Centre for Contact Lens Research. The next morning, lenses were removed, and thickness measurements were repeated 1, 3, 6, and 12 h after removal. RESULTS: On lens removal, the MenZ eye had central and paracentral corneal swelling (mean +/- SD) of 4.1 +/- 2.0% and 5.6 +/- 2.4%, and the EqII eye had 5.8 +/- 2.6% and 7.0 +/- 2.6%. These values were significantly different from baseline (ReANOVA; p < 0.001) and were different between lens materials (p < 0.001). The central epithelium thinned by 10.0 +/- 4.5% in the MenZ eye and by 10.2 +/- 8.5% in the EqII eye, with the mid-peripheral epithelium thickening by 13.4 +/- 7.9% in the MenZ eye and 18.3 +/- 9.8% in the EqII eye (all changes different from baseline p < 0.001). These epithelial values were not statistically different between materials (p > 0.05). Stromal swelling values on lens removal were 5.7 +/- 2.2% centrally and 5.5 +/- 3.0% mid-peripherally (MenZ) and 7.7 +/- 3.1% centrally and 6.6 +/- 2.9% mid-peripherally (EqII) (all p < 0.001 from baseline). Central stromal swelling was different between eyes at lens removal (p < 0.001). Stromal thickness in both eyes returned to baseline values within 3 h. CONCLUSION: The higher-Dk/t MenZ material caused significantly less overnight corneal and stromal swelling than the Eqll material, which reinforces the need to prescribe lenses with high Dk/t for overnight wear. Neither central epithelial thinning nor paracentral thickening are significantly affected by Dk/t.

Corneal and epithelial thickness in keratoconus: a comparison of ultrasonic pachymetry, Orbscan II, and optical coherence tomography.

PURPOSE: To compare corneal thickness measurements in individuals with keratoconus using optical coherence tomography (OCT), Orbscan II, and ultrasonic pachymetry and to measure epithelial and stromal thickness in these individuals using OCT. METHODS: Twenty individuals with keratoconus and 20 controls (without keratoconus) were enrolled. The Orbscan II was used to locate the steepest area of the cornea, which was taken to represent the cone apex. Each instrument was used to obtain four total corneal thickness measurements-from the cone apex, corneal center, mid-nasal, and mid-temporal cornea. Optical coherence tomography scans were analyzed to provide epithelial and stromal thickness readings. RESULTS: In individuals with keratoconus, mean central corneal thickness (CCT) measured by ultrasonic pachymetry, Orbscan, and OCT was 494.2 +/- 50.0 microm, 438.6 +/- 47.7 microm, and 433.5 +/- 39.7 microm, respectively. The central keratoconic cornea was 57.7 microm thinner than the normal cornea (post-hoc P<.001). The cone apex was thinner than the central cornea (P<.001). Keratoconic epithelium was 48.2 +/- 5.5 microm centrally and 42.1 +/- 4.5 microm at the apex. Central keratoconic epithelium was 4.7 microm thinner and central keratoconic stroma was 57.8 microm thinner than the normal cornea (P<.001, respectively). Comparing instruments, Orbscan and OCT correlated in CCT measurement (r=0.890) and apical thickness (r=0.846). All instruments produced similar readings for mid-nasal and mid-temporal corneal thickness in participants with keratoconus (P>.05). CONCLUSIONS: Ultrasonic pachymetry produced the highest corneal thickness readings in the center and apex, compared to Orbscan II and OCT. Centrally, the total cornea, epithelium, and stroma were thinner in individuals with keratoconus than in normal individuals.

Corneal and epithelial thickness changes after 4 weeks of overnight corneal refractive therapy lens wear, measured with optical coherence tomography.

PURPOSE: To investigate thickness changes of the total cornea and epithelium across the horizontal corneal meridian after 4 weeks of overnight corneal refractive therapy (CRT) rigid contact lens (Paragon Vision Sciences, Mesa, AZ) wear. METHODS: Thirty subjects were fitted with CRT contact lenses (Dk/t = 67), which were worn overnight for 4 weeks. Corneal thickness was measured at nine locations along the horizontal meridian by using optical coherence tomography (OCT) before lens insertion in the evening. Corneal thickness was measured the next morning immediately after lens removal and 1, 3, 7, and 14 hours later. This was repeated on days 4, 10, and 28 of the study and then 3 days after discontinuing lens wear. RESULTS: Twenty-three subjects completed the study. At lens removal on day 1, the central and paracentral cornea swelled by 4.9% and 6.2%, respectively (both P = 0.000). The central epithelium thinned by 7.3%, and the mid peripheral epithelium thickened by 13% (both P = 0.000). Corneal swelling recovered throughout the day, with most of the deswelling taking place within the first 3 hours after lens removal. Maximal central epithelial thinning reached 13.5% by day 4. Three days after the study completion, corneal and epithelial thickness had recovered to baseline values. CONCLUSIONS: This study shows that CRT lenses induce differential overnight swelling across the cornea, with rapid deswelling during the day. Central epithelial thinning and paracentral thickening occurs, with recovery 3 days after discontinuation of lens wear.