Recharacterization of superior limbic keratoconjunctivitis via a subdividing grading method in 236 Chinese patients.

PURPOSE: Superior limbic keratoconjunctivitis (SLK) is an uncommon and often overlooked chronic ocular surface disease. This retrospective consecutive case series study on Chinese patients aimed to characterize the features of this disease, including those undescribed in previous literature. METHODS: Two hundred thirty-six patients diagnosed with SLK were enrolled into this consecutive case study from 2016 to 2019. The demographics, symptoms, Ocular Surface Disease Index, and ocular signs were collected and analyzed. A scoring system (SLK scale index, SSI) that integrated five major sign scores was applied to evaluate SLK severity. RESULTS: Of the 236 SLK patients, dryness was the most common complaint (59.3%). Of 459 SLK eyes, superior limbus/conjunctival staining (SCS) was present in 98% eyes, followed by the superior tarsal conjunctival alterations (85.2%) and superior bulbar conjunctiva hyperemia (80.8%). Approximately 63% of eyes were accompanied by corneal staining. Superior bulbar conjunctivochalasis was a relatively rare sign (41.6%). Among the five major signs, only the prevalence of SCS gradually increased with its severity. In addition, fluorescein staining at the inferior limbus and adjacent conjunctiva (ICS) was found positive in 163 eyes of 84 patients (36%) who had significantly higher SSI than those without ICS (p = 0.013). CONCLUSIONS: We found that SCS is the most common out of the 5 typical signs of SLK. ICS, a new sign, occurred in one-third of patients. SCS, a simple marker of SLK, as well as SSI, an integrated evaluation system, had the advantage of evaluating the severity and objectively characterizing SLK in clinical practice.

Compatibility of a New Ocular Surface Dye with Disposable and Bi-Weekly Soft Contact Lenses: An Experimental Study.

Ocular surface staining for assessing corneal and conjunctival epithelium integrity is typically conducted using fluorescein, lissamine green, or rose Bengal dyes. Recently, a novel vital dye, REmark®, based on riboflavin, has been proposed for ocular surface examination. In the management of corneal and ocular surface diseases (OSD), the use of contact lenses is integral to therapeutic strategies. This study explores the compatibility of REmark® with four different types of disposable or bi-weekly soft contact lenses. Morphological variations observed under stereomicroscopy and ultraviolet (UV) ray transmittance in the visible spectrum (VIS) were evaluated at 2 and 4 h post-immersion of the contact lenses in both the original fluid and the new dye. The findings indicate no significant differences between the group treated with the original liquid and those immersed in REmark®, except for a yellow hue observed in the latter group, which dissipates after 8 h in physiological solution. This study highlights the potential of utilizing the new vital dye for ophthalmologic examinations even in the presence of applied soft contact lenses, offering a promising avenue for improved diagnostic practices and patient comfort.

Efficacy and Safety of the Melanocortin Pan-Agonist PL9643 in a Phase 2 Study of Patients with Dry Eye Disease.

Purpose: The melanocortin receptor pan-agonist PL9643, a potential therapy for ocular diseases, was investigated in a phase 2, 12-week study in patients with dry eye disease (DED). Methods: This was a placebo-controlled study evaluating efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to tears. Primary endpoints were intra-patient changes in inferior corneal fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints were changes in additional DED signs or symptoms. Multiple secondary endpoints were not adjusted for multiplicity. Patients with moderate or severe DED were analyzed in addition to the overall intent-to-treat (ITT) population. Results: In the ITT population (n = 160) the PL9643 group did not demonstrate significant treatment difference versus placebo at week 12/day 85 for the primary endpoints (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) improvement over placebo in mean change from baseline at week 12/day 85 in several sign endpoints, including fluorescein staining in inferior, superior, corneal sum, and total sum regions; Lissamine Green staining in temporal, nasal, conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival redness also showed (nonsignificant) improvement at week 12/day 85. There were no drug-related adverse events (AEs) and no drug-related discontinuations. Conclusions: PL9643 showed no significant efficacy for the ITT population; however, efficacy results across several signs and symptoms in the subpopulation of moderate to severe DED patients, the low number of ocular AEs, and no tolerability issues suggest that PL9643 shows promise as a therapeutic for DED. Clinical Trial Registration number: NCT04268069.

Effect of OTX-101 in Patients with Dry Eye Disease at Day 14 of Treatment: Ocular Surface Endpoint Results from the Phase 2b/3 Clinical Trial.

Dry eye disease (DED) is a multifactorial disorder characterized by loss of tear film homeostasis, which initiates a cycle of ocular surface inflammation and damage. As ocular discomfort symptoms associated with DED can decrease quality of life, affected patients prefer treatments that rapidly improve the underlying disease process. OTX-101 0.09% (CEQUA®) is indicated to increase tear production in patients with DED. The current analysis assessed early efficacy of OTX-101 0.09% in adult patients with bilateral DED by evaluating ocular surface endpoints after 14 days of treatment in the phase 2b/3 trial. In this randomized, double-masked, vehicle-controlled, dose-ranging study, patients received one drop of OTX-101 0.05%, OTX-101 0.09%, or vehicle per eye twice daily for 84 days. Corneal staining, conjunctival staining, tear breakup time (TBUT), and modified Symptom Assessment iN Dry Eye (SANDE) total global symptom score were assessed at baseline and Days 14, 28, 42, 56, and 84/early discontinuation. Overall, 455 patients were randomized (OTX-101 0.05%, n=151; OTX-101 0.09%, n=152; vehicle, n=152); only baseline and Day 14 results for the approved OTX-101 0.09% formulation and vehicle are presented. Least squares (LS) mean (standard error [SE]) change from baseline in conjunctival staining score was -1.3 (0.1) for OTX-101 and -1.0 (0.1) for vehicle. LS mean (SE) change from baseline in corneal staining score was -1.1 (0.17) for OTX-101 and -0.7 (0.17) for vehicle. LS mean (SE) change from baseline in TBUT was 0.52 (0.15) for OTX-101 and 0.36 (0.15) for vehicle. LS mean (SE) change from baseline in modified SANDE total global symptom score was -4.93 (1.54) for OTX-101 and -9.1 (1.54) for vehicle. OTX-101 0.09% demonstrated a numerically greater treatment effect compared with vehicle in conjunctival staining, corneal staining, and TBUT after 14 days.

Impact of upper blepharoplasty, with or without orbicularis oculi muscle removal, on tear film dynamics and dry eye symptoms: A randomized controlled trial.

PURPOSE: Upper blepharoplasty may be related to dry eye symptoms since the function of the orbicularis oculi muscle may affect the tear film. We aimed to assess the effect of blepharoplasty with or without the removal of a strip of orbicularis oculi muscle on tear film dynamics and dry eye symptoms. METHODS: A double-blind, randomized, controlled trial comparing upper blepharoplasty without (group A) or with (group B) orbicularis oculi muscle excision was performed on 54 healthy Caucasian patients. Tear film dynamics and dry eye symptoms were evaluated using multiple dry eye parameters, i.e. tear osmolarity, Schirmer test I, corneal/conjunctival staining, tear break-up time (TBUT), Oxford Scheme, Sicca Ocular Staining Score and Ocular Surface Disease Index questionnaire. All the parameters were assessed preoperatively and 6 and 12 months after upper blepharoplasty. All the groups' outcomes were compared. RESULTS: The differences were not significant between the two upper blepharoplasty techniques regarding most of the above-mentioned outcomes. Subjective symptoms of ocular irritation, consistent with dry eye disease and vision-related impairment, were reduced after upper blepharoplasty independent of the type of the technique applied, while the pre and postoperative outcomes of the objective tear dynamics did not differ 12 months after surgery. However, group B demonstrated a significant increase in tear osmolarity and TBUT at the 6-month follow-up visit. CONCLUSION: An upper blepharoplasty alleviates subjective dry eye complaints in the long term, while not changing the tear dynamics. The improvement was independent of the blepharoplasty technique used.

Clinical significance of contact lens related changes of ocular surface tissue observed on optical coherence images.

PURPOSE: To investigate the relationship between the real contact lens imprint into the conjunctival tissue, observed by optical coherence tomography (OCT) and conjunctival staining and contact lens wearing comfort. METHODS: 17 participants (mean age = 26.6 SD ± 3.6 years; 7 females) were fitted with three different contact lenses base curves of the same silicone hydrogel custom lens type (Visell 50; Hecht Contactlinsen, Au, Germany) in a randomised order. One lens was optimally fitted according to the manufacturer's recommendation, one fitted 0.4 mm flatter and one fitted 0.4 mm steeper. After 4 h of lens wear the contact lens edge in the area of the conjunctiva was imaged nasally and temporally using OCT (Optovue iVue SD-OCT). To correct the artefact due to optical distortion with OCT, the imprint of all worn lenses was measured on a glass plate afterwards. Conjunctival staining in the limbal region after 4 h of lens wear was classified using the CCLRU Grading Scale. Comfort scoring was based on visual analog scales from 0 (very poor) to 100 (excellent). RESULTS: The mean conjunctival imprint of all contact lens edges was 32.0 ± 8.1 µm before and 7.3 ± 6.5 µm after distortion correction of the OCT images. The distortion corrected conjunctival imprint with the 0.4 mm steeper lens (11.5 ± 6.2 µm) was statistically significantly greater compared to the optimally fitted lens (6.5 ± 5.9 µm) (One-way ANOVA followed Tukey-test; p = 0.017) and greater compared to the 0.4 mm flatter lens (3.9 ± 5.3 µm) (p < 0.001). There was no statistically significant difference between the optimally fitted lens and the 0.4 mm flatter lens (p = 0.209). The nasally measured imprint (11.4 ± 9.0 µm) was significantly greater than the temporally measured (3.3 ± 7.6 µm) (p < 0.001). There was no statistically significant correlation between the amount of conjunctival imprint and the graded conjunctival staining (p = 0.346) or the wearer's comfort (p = 0.735). CONCLUSIONS: Contact lens edges imaged by OCT exhibited displacement artefacts. The observed conjunctival imprints are a combination of real conjunctival compression and artefacts. A deeper imprint of the contact lens into the conjunctiva caused by a steeper base curve was not related to clinically significant staining or changes in comfort after 4 h of lens wear. The observed differences between nasal and temporal imprint are likely to be caused by variations of conjunctival thickness and the shape of the underlying sclera.

Daily versus monthly disposable contact lens: Which is better for ocular surface physiology and comfort?

PURPOSE: To investigate the effect of soft contact lenses (SCL) wearing modality and lens materials on the changes in conjunctival bulbar and limbal redness and conjunctival and corneal staining after two months of SCL wear. Comfort level was also analyzed. METHODS: In this longitudinal clinical trial, forty-seven neophyte myopic subjects were fitted with a monthly disposable lens (lotrafilcon-B or comfilcon-A or balafilcon-A) in one eye and a daily disposable lens (nelfilcon-A or stenofilcon-A or nesofilcon-A) in the other eye, randomly selected. Conjunctival bulbar and limbal redness and conjunctival and corneal staining were evaluated before and after lens wear. Effect of lens wearing modality and lens materials on these changes was also determined. Level of comfort was evaluated subjectively twice per day. Comfort level and reduction in end-of-day comfort were compared between different lens wearing modalities and materials. RESULTS: Bulbar and limbal redness and conjunctival and corneal staining were increased (p<0.001) after lens wear, and changes were similar with daily and monthly disposable lens wear (p>0.05). Limbal redness was associated with lens materials, and lotrafilcon-B induced the least among the studied lenses (p<0.05). There was no significant association between the wearing modality and the average comfort level and reduction of end-of-day comfort (p>0.05). CONCLUSION: Two months of SCL wear increased conjunctival redness, conjunctival and corneal staining, which were not associated with the lens wearing modality. There was a reduction in end-of-day comfort, similar to daily and monthly lenses. The change in limbal redness and reduction in end-of-day comfort were associated with the characteristics of the lens material.

Effects of Systane(®) Balance on noninvasive tear film break-up time in patients with lipid-deficient dry eye.

PURPOSE: To evaluate the ability of Systane(®) Balance (SYSB) administered four times per day for 4 weeks to increase noninvasive tear film break-up time (NITFBUT) over baseline compared with a saline (SAL) control in patients with lipid-deficient dry eye (DE). PATIENTS AND METHODS: Patients aged ≥18 years with DE and evidence of meibomian gland dysfunction (ie, abnormal gland expression and missing meibomian glands) were included in this randomized, parallel-group, controlled, investigator-masked comparison study. Patients were randomized to SYSB or SAL four times daily for 4 weeks. The primary efficacy variable was mean change in NITFBUT from baseline at week 4. Ocular surface staining, goblet cell density, and meibomian gland expression were also assessed. Safety assessments included adverse events (AEs), best-corrected visual acuity, and ocular signs. RESULTS: A total of 49 patients received study treatments (SYSB, n=25; SAL, n=24). Most patients were women (67.4%) and Caucasian (63.3%); mean ± standard deviation (SD) age was 44±19 years. DE characteristics at baseline were similar between groups. After 4 weeks of treatment, the mean ± SD NITFBUT increase from baseline was significantly greater with SYSB (2.83±0.74 seconds) compared with SAL (0.66±0.55 seconds; P<0.001, t-test). Improvements in conjunctival and corneal staining, percentage of patients with increased goblet cell density, and meibomian gland expression were also observed with 4 weeks of SYSB over SAL. No AEs were reported for either treatment group; best-corrected visual acuity and ocular signs remained stable or improved compared with baseline. CONCLUSION: SYSB restored tear film stability, improved ocular surface healing, and improved meibomian gland functionality after 4 weeks of use in patients with lipid-deficient DE. No AEs were reported with either SYSB or SAL.