In Vitro and In-Eye Comparison of Commercial Pilocarpine Ophthalmic Solution and an Optimized, Reformulated Pilocarpine for Presbyopia Treatment.

INTRODUCTION: Pilocarpine hydrochloride (pilo) ophthalmic solution has traditionally been used for the treatment of glaucoma, with opportunities to improve the tolerability profile experienced by patients. Pilocarpine hydrochloride ophthalmic solution 1.25% (Vuity™, Allergan, an AbbVie company) was approved in late 2021 for the treatment of adults with presbyopia. This publication describes the properties of the optimized, proprietary vehicle of this new ophthalmic solution developed with the aim of improving tolerability upon instillation. METHODS: An in vitro method determined the time required for the pH of pilo 1.25% in the proprietary vehicle (Optimized Formulation) and a commercially available 1% pilo ophthalmic solution (Generic Formulation) to equilibrate with the pH of simulated tear fluid (STF). In a pilot study, five of the six screened participants received one drop of the Optimized Formulation in one eye and Generic Formulation in the other. Ocular discomfort and vision blur were evaluated for each eye just prior to and at multiple times after drop instillation using visual analog scales (VAS), and adverse events were assessed. RESULTS: The in vitro method showed that the Optimized Formulation achieved faster pH equilibration than the Generic Formulation. The pilot study revealed that the Optimized Formulation demonstrated less ocular discomfort, vision blur, and adverse events compared to the Generic. CONCLUSION: The in vitro and pilot study of the Optimized Formulation indicated that it rapidly equilibrates to the physiologic pH of the tear film, providing greater comfort and tolerability while also minimizing vision blur. Overall, the proprietary vehicle is expected to improve comfort, result in less vision blur, and provide a well-tolerated alternative method to deliver pilo for the treatment of presbyopia when compared to what is commercially available.

TearCare for the Treatment of Meibomian Gland Dysfunction in Adult Patients With Dry Eye Disease: A Masked Randomized Controlled Trial.

PURPOSE: The aim of this study was to demonstrate the safety and effectiveness of a single TearCare procedure compared with a single LipiFlow procedure in treatment of the dry eye disease associated with meibomian gland dysfunction. METHODS: In a multicenter, masked, randomized controlled trial, 135 subjects received a single TearCare (TC) treatment (n = 67) or a single LipiFlow (LF) treatment (n = 68) at baseline and were followed up for 1 month posttreatment. Tear film breakup time, meibomian gland function, and corneal and conjunctival staining scores were assessed as dry eye signs at baseline, 2 weeks, and 1 month; dry eye symptoms were assessed using the Ocular Surface Disease Index, Symptom Assessment in Dry Eye, and eye dryness questionnaires at baseline and 1 month. RESULTS: At 1 month posttreatment, both groups demonstrated significant improvements (P < 0.0001) in mean tear film breakup time and meibomian gland secretion score to 3.0 ± 4.4 and 11.2 ± 11.1 in the TC group and 2.6 ± 3.3 and 11.0 ± 10.4 in the LF group, respectively. The mean eye dryness, Symptom Assessment in Dry Eye, and Ocular Surface Disease Index scores were significantly reduced (P < 0.0001) by 35.4 ± 34.1, 38.2 ± 31.0, and 27.9 ± 20.5 in the TC group and 34.9 ± 26.9, 38.0 ± 25.9, and 23.4 ± 17.7 in the LF group, respectively. There were no statistically significant differences for any result between the groups. However, the TC group demonstrated numerically greater improvements consistently in all signs and symptoms. Device-related ocular adverse events were reported in 3 patients in the TC group (superficial punctate keratitis, chalazion, and blepharitis) and 4 patients in the LF group (blepharitis, 2 cases of foreign body sensation, and severe eye dryness). CONCLUSIONS: A single TearCare treatment significantly alleviates the signs and symptoms of dry eye disease in patients with meibomian gland dysfunction and is equivalent in its safety and effectiveness profile to LipiFlow treatment as shown in this 1-month follow-up study.

Efficacy of Lifitegrast Ophthalmic Solution, 5.0%, in Patients With Moderate to Severe Dry Eye Disease: A Post Hoc Analysis of 2 Randomized Clinical Trials.

IMPORTANCE: An investigation of the treatment effect of lifitegrast ophthalmic solution, 5.0%, in different subgroups by severity of dry eye disease (DED) seems warranted. OBJECTIVE: To explore the heterogeneity across different subgroups of DED and identify which participants were most likely to achieve clinically meaningful benefit with lifitegrast treatment. DESIGN, SETTING, AND PARTICIPANTS: This post hoc responder analysis was performed using the data from the phase 3 OPUS-2 and OPUS-3 studies, which were 12-week, prospective, double-masked, multicenter, placebo-controlled, randomized, parallel-arm clinical trials that previously demonstrated the efficacy of lifitegrast in DED. Pooled data were stratified into 4 subgroups based on severity of inferior corneal staining score (ICSS; ≤1.5 vs >1.5) and eye dryness score (EDS; <60 or ≥60) at baseline. Data were collected from December 7, 2012, to October 5, 2015, and post hoc analysis was performed from April 14, 2020, to July 30, 2021. INTERVENTIONS: Lifitegrast or placebo twice daily for 84 days. MAIN OUTCOMES AND MEASURES: Proportion of participants with (1) a clinically meaningful improvement in signs (ICSS or total corneal staining score [TCSS]) and symptoms (EDS or global visual analog scale [VAS]) and (2) a composite response for a given sign and symptom end point pair at day 84 were measured. Clinically meaningful improvement was defined as at least 30% improvement in symptoms (EDS or global VAS) and either at least a 1-point improvement in ICSS or at least a 3-point improvement in TCSS. For the composite responder analysis, the end point pairs were defined as at least a 30% reduction in EDS and at least a 1-point improvement in ICSS; at least a 30% reduction in EDS and at least a 3-point improvement in TCSS; at least a 30% improvement in global VAS and at least a 1-point improvement in ICSS; and at least a 30% improvement in global VAS and at least a 3-point improvement in TCSS. RESULTS: In total, 1429 participants (716 in the placebo group and 713 in the lifitegrast group) were analyzed (1087 women [76.1%]; mean [SD] age, 58.7 [14.3] years). For the overall pooled population, responder and composite responder rates favored lifitegrast vs placebo (odds ratio range, 1.29 [95% CI, 1.05-1.59] to 2.10 [95% CI, 1.68-2.61]; P ≤ .02). In the composite analysis, the subgroup with ICSS of greater than 1.5 and EDS of at least 60 at baseline (ie, moderate to severe DED) demonstrated a 1.70- to 2.11-fold higher odds of achieving clinically meaningful improvement with lifitegrast across all sign and symptom end point pairs (P ≤ .001). CONCLUSIONS AND RELEVANCE: These post hoc findings suggest that lifitegrast ophthalmic solution, 5.0%, treatment may be associated with a response in participants with moderate to severe signs and symptoms of DED. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02284516.

Prevention and management of refractive prediction errors following cataract surgery.

Patient satisfaction after modern day cataract surgery requires excellent surgical technique but increasingly demands superior refractive outcomes as well. In many cases, there exists an expectation from patients, as well as surgeons, to achieve emmetropia after cataract surgery. This is particularly true in patients electing premium intraocular lens technology to correct astigmatism and presbyopia to minimize spectacle dependence. Despite continued advances in preoperative and intraoperative diagnostics, refractive planning, and surgical technology, residual refractive error remains a primary source of dissatisfaction after cataract surgery. The need to enhance refractive outcomes and treat residual astigmatic or spherical refractive errors postoperatively becomes paramount to meeting the expectations of patients in their surgical outcome. This article reviews the potential preoperative and intraoperative pitfalls that can be the source of refractive error, the various options to enhance refractive outcomes, and potential future technologies to limit residual refractive error after cataract surgery.

Optimum Refractive Target in Patients with Bilateral Implantation of Extended Depth of Focus Intraocular Lenses.

PURPOSE: To determine the refractive target of extended depth of focus (EDOF) intraocular lenses in dominant and non-dominant eyes which provides the best binocular vision at all ranges after cataract surgery. PATIENTS AND METHODS: This retrospective, single-center, non-comparative study included 47 patients who had undergone bilateral cataract surgery with implantation of EDOF IOLs (Tecnis Symfony or Tecnis Symfony Toric) targeting emmetropia in both eyes. Binocular uncorrected visual acuity at distance (UDVA), near (UNVA), intermediate (UIVA), and manifest refraction spherical equivalent (MRSE) were recorded between 1 and 3 months after the second-eye cataract surgery. Scattergrams for combined binocular UDVA, UIVA, UNVA and postoperative MRSE were plotted and the points of minima of the quadratic regression curve for the dominant and non-dominant eyes were considered as the optimum MRSE corresponding to the best overall visual acuity. Subgroup analysis of patients who achieved UDVA and UIVA ≥20/20 and UNVA ≥20/30 was also performed. RESULTS: For the overall group, the optimum MRSE was -0.08 D for dominant and -0.63 D for non-dominant eyes. In a subset of 17 patients who achieved excellent acuity at all distances, the mean MRSE for the dominant and non-dominant eyes was -0.07 ± 0.14 D and -0.21 ± 0.24 D, respectively. CONCLUSION: Excellent visual acuity at all ranges can be achieved with bilateral EDOF intraocular lenses implanted after cataract surgery. Our results indicate the best results when the dominant eye is targeted at emmetropia and the nondominant eye is targeted between -0.21D and -0.63D, with excellent results shown with mild myopia of -0.21 in the non-dominant eyes. Future studies with larger sample sizes and subjective patient-reported outcomes may validate current study outcomes.

Visual outcomes 24 months after LaserACE.

BACKGROUND: To evaluate the effects on near and intermediate visual performance after bilateral Laser Anterior Ciliary Excision (LaserACE) procedure. METHODS: LaserACE surgery was performed using the VisioLite 2.94 µm erbium: yttrium-aluminum-garnet (Er:YAG) ophthalmic laser system in 4 oblique quadrants on the sclera over the ciliary muscle in 3 critical zones of physiological importance (over the ciliary muscles and posterior zonules) with the aim to improve natural dynamic accommodative forces. LaserACE was performed on 26 patients (52 eyes). Outcomes were analyzed using visual acuity testing, Randot stereopsis, and the CatQuest 9SF patient survey. RESULTS: Binocular uncorrected near visual acuity (UNVA) improved from +0.20 ± 0.16 logMAR preoperatively, to +0.12 ± 0.14 logMAR at 24 months postoperatively (p = 0.0014). There was no statistically significant loss in distance corrected near visual acuity (DCNVA). Binocular DCNVA improved from +0.21 ± 0.17 logMAR preoperatively, to +0.11 ± 0.12 logMAR at 24 months postoperatively (p = 0.00026). Stereoacuity improved from 74.8 ± 30.3 s of arc preoperatively, to 58.8 ± 22.9 s of arc at 24 months postoperatively (p = 0.012). There were no complications such as persistent hypotony, cystoid macular edema, or loss of best-corrected visual acuity (BCVA). Patients surveyed indicated reduced difficulty in areas of near vision, and were overall satisfied with the procedure. CONCLUSIONS: Preliminary results of the LaserACE procedure show promising results for restoring visual performance for near and intermediate visual tasks without compromising distance vision and without touching the visual axis. The visual function and visual acuity improvements had clinical significance. Patient satisfaction was high postoperatively and sustained over 24 months. TRIAL REGISTRATION: NCT01491360 (https://clinicaltrials.gov/ct2/show/NCT01491360). Registered 22 November 2011.

Intracameral ketorolac and phenylephrine effect on intraoperative pupil diameter and postoperative pain in cataract surgery.

PURPOSE: To evaluate the study drug OMS302 (Omidria [phenylephrine and ketorolac injection 1.0%/0.3%]) compared with a balanced salt solution (vehicle), ketorolac, and phenylephrine on pupil diameter during cataract surgery and early postoperative ocular pain. SETTING: Twenty-three centers in the United States. DESIGN: Randomized clinical trial. METHODS: Patients were randomized (1:1:1:1) to receive vehicle, phenylephrine, ketorolac, or the study drug containing phenylephrine and ketorolac administered intracamerally during surgery. Intraoperative pupil diameter was determined each minute by video capture. Postoperative ocular pain was evaluated for up to 12 hours. RESULTS: The study evaluated 223 patients. The study drug was significantly better than the vehicle and ketorolac in maintaining mydriasis (least-squares mean differences 0.9 ± 0.1 [SEM] and 0.7 ± 0.1 for the study drug versus vehicle and ketorolac, respectively; P < .0001 each). Ocular pain assessed using the Visual Analog Scale was significantly reduced for the study drug compared with the vehicle or phenylephrine (least-squares mean difference -4.6 ± 2.2 and P = .042 and 5.9 ± 2.2 and P = .009, respectively). Significantly fewer patients treated with the study drug (3 [6.1%]) had an intraoperative pupil diameter smaller than 6.0 mm compared with those treated with the vehicle (25 [47.2%]; P < .0001), ketorolac (18 [34.6%]; P = .0004), or phenylephrine (11 [22.4%]; P = .0216). CONCLUSIONS: The study drug was safe and efficacious in maintaining mydriasis and reducing postoperative ocular pain. Both ketorolac and phenylephrine contributed to the therapeutic effects, with the combination showing superiority to either agent alone in maintaining an intraoperative pupil diameter of 6.0 mm or larger.

Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3).

PURPOSE: Lifitegrast is a lymphocyte function-associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED. DESIGN: Twelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study. PARTICIPANTS: Adults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0-4 scale), eye dryness score (EDS) ≥40 (0-100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry. METHODS: After a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. MAIN OUTCOME MEASURES: The primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo. RESULTS: In the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04-11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44-13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33-11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported. CONCLUSIONS: Lifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

A retrospective analysis of the postoperative use of loteprednol etabonate gel 0.5% following laser-assisted in situ keratomileusis or photorefractive keratectomy surgery.

BACKGROUND: While loteprednol etabonate ophthalmic gel 0.5% (LE gel) is approved for treatment of postoperative ocular inflammation and pain, there have been no reported studies in patients undergoing laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). METHODS: This was a retrospective chart review conducted at five refractive surgical centers in the USA. Data were collected from primary LASIK or PRK surgery cases in which LE gel was used postoperatively as the clinician's routine standard of care and in which patients were followed-up for up to 6 months. Data extracted from charts included patient demographics, surgical details, LE gel dosing regimen, pre- and postsurgical refractive characteristics, intraocular pressure (IOP) measurements, and visual acuity. Primary outcomes included postoperative IOP elevations, adverse events, and early discontinuations. RESULTS: Data were collected on 189 LASIK eyes (96 patients) and 209 PRK eyes (108 patients). Mean (standard deviation [SD]) years of age at surgery was 36.0 (11.7) and 33.9 (11.3) in LASIK and PRK patients. LE gel was prescribed most often four times daily during the first postoperative week, regardless of procedure; the most common treatment duration was 7-14 days in LASIK and ≥30 days in PRK patients. No unusual corneal findings or healing abnormalities were reported. Mean postoperative uncorrected distance visual acuity was 20/24 in LASIK and 20/30 in PRK eyes. Mild/trace corneal haze was reported in 20% of PRK patients; two PRK patients with moderate/severe corneal haze were switched to another corticosteroid. Mean postoperative IOP did not increase over time in either LASIK or PRK eyes (P≥0.331); clinically significant elevations from baseline in IOP (≥10 mmHg) were noted in only three eyes of two PRK patients. CONCLUSION: LE gel appears to have a high level of safety and tolerability when used for the management of postoperative pain and inflammation following LASIK and PRK surgery.

The efficacy of bromfenac ophthalmic solution 0.07% dosed once daily in achieving zero-to-trace anterior chamber cell severity following cataract surgery.

PURPOSE: To evaluate the efficacy of bromfenac ophthalmic solution 0.07% dosed once daily in achieving zero-to-trace (0-5 cells) anterior chamber cells, following cataract surgery with posterior chamber intraocular lens implantation. METHODS: The study designed employed two Phase III, double-masked, placebo-controlled, multicenter clinical trials of 440 subjects, randomized to either bromfenac ophthalmic solution 0.07% (n=222) or placebo (n=218). Subjects self-dosed once daily, beginning 1 day before undergoing cataract surgery with intraocular lens implantation (day -1) and again on the day of surgery (day 0) and for 14 days postoperatively. Follow-up was on days 1, 3, 8, and 15. The outcome measures included the percentage of subjects with zero-to-trace anterior chamber cells at each visit, as determined by the percentage of subjects with ≤5 anterior chamber cells, overall anterior chamber cell grades, and summed ocular inflammation score (SOIS) (combined anterior chamber cell and flare scores). RESULTS: The proportion of subjects with zero-to-trace anterior chamber cells was significantly higher in the bromfenac 0.07% group compared with the placebo group as early as day 3 (P=0.0007), continued at day 8 (P<0.0001), and through day 15 (P<0.0001). At day 15, 80.2% of subjects in the bromfenac 0.07% group achieved zero-to-trace anterior chamber cells compared with 47.2% of subjects who did so in the placebo group. The overall anterior chamber cell scores were significantly lower in the bromfenac 0.07% group compared with the placebo group at days 3, 8, and 15 (P<0.0001 at each visit). The SOIS were also significantly lower in the bromfenac group compared with the placebo group at days 3, 8, and 15 (P<0.0001 at each visit). CONCLUSION: Bromfenac ophthalmic solution 0.07%, dosed once daily was clinically effective in achieving zero-to-trace anterior chamber cell severity after cataract surgery and was superior to placebo in all anterior chamber cell severity and inflammation outcome measures.

Efficacy of a new prescription-only medical food supplement in alleviating signs and symptoms of dry eye, with or without concomitant cyclosporine A.

PURPOSE: To evaluate the effect of a new, prescription-only medical food supplement containing omega-3 and omega-6 essential fatty acids on dry eye signs and symptoms, with or without concomitant topical cyclosporine. METHODS: A total of 43 subjects were randomized and followed for 6 months. Group 1 (n = 23) was assigned to take two soft geltabs of the medical food supplement by mouth twice daily for 6 months. Group 2 (n = 20) was directed to take the medical food supplement in the same manner, along with topical cyclosporine, instilled twice daily during the last 3 months of the study. Subjects were evaluated at baseline, month 1, month 3, and month 6. Primary outcome measures included tear breakup time (TBUT), conjunctival staining, corneal staining, and change in subjective symptoms. RESULTS: Both groups had a statistically significant improvement in TBUT between baseline and month 6. In the food supplement only group, TBUT improved by 0.805 seconds from baseline to month 6. In the supplement/cyclosporine group, TBUT improved by 1.007 seconds from baseline. There was no statistically significant difference in TBUT between the two groups at baseline, month 3, or month 6. There were no significant differences in corneal or conjunctival staining between or within groups. Subjective symptoms were also improved in both groups. CONCLUSION: Supplementation with the proper balance of omega-3 and omega-6 essential fatty acids improved TBUT and relieved patient symptoms. The addition of topical cyclosporine did not convey any statistically significant improvement in TBUT beyond that achieved by the supplement.