Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Private equity has made significant inroads into the specialty of ophthalmology. The purpose of this review is to evaluate the effect of private equity on clinical operations in an ophthalmic practice. RECENT FINDINGS/RESULTS:Private equity had become an important source of capital and management expertise that has resulted in the consolidation of many ophthalmic practices as an alternative to working for a hospital system, insurance carrier, or independent private practice. SUMMARY/CONCLUSIONS:The recent growth of private equity presence in ophthalmology has resulted in significant changes in clinical operations. These changes in clinical operations include the increased importance of data management and data analytics, economies of scale, synergies, and introduction of patient-shared billing opportunities. Although physician input into clinical operations is decreased, provisional care decision-making can be maintained.

Purpose/UNASSIGNED:To assess the frequency of patients reducing the use of artificial tears (ATs) among patients with dry eye disease (DED) following lifitegrast treatment. Patients and Methods/UNASSIGNED:Two independent analyses were performed using the data from the 1-year, randomized, multicenter, Phase 3 SONATA trial and a noninterventional, real-world evidence (RWE) study conducted in patients with DED who were treated with lifitegrast in the United States and Canada. In SONATA, patients who had used ATs in the lifitegrast and placebo groups were included. The RWE study reviewed patients' electronic medical records, prescribing patterns, and practices of physicians throughout the survey. These data were then used to compare the proportion of patients using ATs in the 6-month pre-index period versus the 12-month post-index period. Results/UNASSIGNED:Of 293 patients (lifitegrast, n=195; placebo, n=98) from SONATA, 107 (lifitegrast, n=64; placebo, n=43) used ATs during the on-therapy period while 186 (lifitegrast, n=131; placebo, n=55) did not. Of those not using ATs, the proportion of patients in the lifitegrast group at any time was higher (~67% [n=131]) versus placebo (~56% [n=55]); this was the case at all study time-points (Days 90, 180, 270, and 360). The RWE study included 600 patient charts (US, n=550; Canada, n=50); 75.5% (n=453) reported AT use. There was ~40% decrease in the proportion of patients using ATs as adjunct DED therapy to lifitegrast in the post-index period (n=273) versus those in the pre-index period (n=453). Conclusion/UNASSIGNED:The findings show that the reliance on AT use can be gradually reduced with lifitegrast treatment, eventually leading to a reduction in disease burden.

Importance/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:Lifitegrast or placebo twice daily for 84 days. Main Outcomes and Measures/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02284516.

PURPOSE/OBJECTIVE:To evaluate the safety and efficacy of a nepafenac punctal plug delivery system (N-PPDS) following cataract surgery. SETTING/METHODS:Three U.S. clinical sites DESIGN:: Prospective, multicenter, randomized (2:1), parallel-arm, double-masked, placebo-controlled, phase II pilot study. METHODS:Fifty-six subjects (age>22 years) with expected post-cataract correctable distance vision of 20/30 or better and lower puncta allowing dilation up to 1.0 mm received either the nepafenac (N-PPDS group; n=38 eyes) or a placebo punctal plug delivery system (p-PPDS group; n=18 eyes). All eyes underwent routine unilateral cataract surgery with intraocular lens implantation. The primary and secondary efficacy measures were postoperative ocular pain and inflammation, respectively. RESULTS:The N-PPDS group had a significantly higher percentage of pain-free patients than the p-PPDS group (69% (22/32) vs 38% (6/16) at Day 3; p=0.038 & 67% (24/36) vs 31% (5/16) at Day 7; p=0.018). A higher percentage of patients in the N-PPDS group (52% (15/29) vs 0% (0/14) (p-PPDS)) was pain free at all visits (p=0.001). Anterior chamber cell scores were better in the N-PPDS group (patients with no anterior chamber cells 50% (18/36) vs 19% (3/16) in p-PPDS; p=0.034) at Day 7. The plug retention rate was 98% (55/56) at 14 days. Adverse events having a suspected relationship with the punctal plug treatment occurred in 1 case of the N-PPDS group having to do with placement and 0 in the p-PPDS group. CONCLUSION/CONCLUSIONS:The N-PPDS was safe and effective for the management of ocular pain and inflammation following cataract surgery.

Presbyopia is a common age-related vision disorder characterized by a progressive inability to focus on near objects. If uncorrected or under-corrected, presbyopia can significantly impact patients' quality of life. Presbyopia represents an area of considerable unmet need due to its rising prevalence worldwide as the population ages, the high proportion of under-treated individuals in some parts of the world, and the limitations of currently available corrective methods. Progressive or bifocal spectacles are associated with peripheral blur, a restricted visual field and impaired depth perception, which have been linked to an increased risk of falls in the elderly. Contact lens options can be difficult to maintain due to the development of age-related dry eye symptoms and reduced manual dexterity. Other corrective methods involve surgical interventions that modify the optics of the cornea, replace the crystalline lens, or attempt to restore active accommodation. While patients undergoing surgery report satisfactory outcomes post-operatively, many of them eventually require reading glasses. Non-invasive therapies with novel mechanisms of action are currently being investigated; these include miotic agents and UNR844, a lipoic acid choline ester. In this narrative review, available evidence on presbyopia prevalence, quality of life impact and risk factors are described, with a focus on observational studies in non-clinical settings. The diagnosis pathway and patient journey in presbyopia are outlined, and various treatment options are analyzed. The data reviewed herein reveals significant gaps in the provision of vision correction for this common condition, with a paucity of effective, non-invasive treatment options broadly accessible to presbyopic individuals.

AIMS/OBJECTIVE:Assess the cost-effectiveness of corneal collagen cross-linking (CXL) versus no CXL for keratoconus in the United States (US). METHODS:A discrete-event microsimulation was developed to assess the cost-effectiveness of corneal cross-linking (CXL, Photrexa + KXL combination product) versus no CXL for patients with keratoconus. The lifetime model was conducted from a US payor perspective. The source for CXL efficacy and safety data was a 12-month randomized, open-label, sham-controlled, multi-center, pivotal trial comparing CXL versus no CXL. Other inputs were sourced from the literature. The primary outcome was the incremental cost per quality-adjusted life year gained. Costs (2019 USD) and effects were discounted 3% annually. The impacts of underlying uncertainty were evaluated by scenario, univariate, and probabilistic analyses. RESULTS:Starting at a mean baseline age of 31 years and considering a mixed population consisting of 80% slow-progressors and 20% fast-progressors, the CXL group was 25.9% less likely to undergo penetrating keratoplasty (PK) and spent 27.9 fewer years in advanced disease stages. CXL was dominant with lower total direct medical costs (-$8,677; $30,994 vs. $39,671) and more QALYs (1.88; 21.80 vs. 19.93) compared to no CXL. Considering the impact of reduced productivity loss in an exploratory scenario, CXL was associated with a lifetime cost-savings of $43,759 per patient. CXL was cost-effective within 2 years and cost-saving within 4.5 years. LIMITATIONS/CONCLUSIONS:Limitations include those that are common to similar pharmacoeconomic models that rely on disparate sources for inputs and extrapolation on short-term outcomes to a long-term analytical horizon. CONCLUSIONS:Keratoconus is a progressive and life-altering disease with substantial clinical, economic, and humanistic consequences. The economic value of cross-linking is maximized when applied earlier in the disease process and/or younger age, and extends to improved work productivity, out-of-pocket costs, and quality of life.

PURPOSE/OBJECTIVE:To assess 5-year effectiveness and safety of 2 iStent® trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) not controlled on 1 medication. MATERIALS AND METHODS/METHODS:This prospective, interventional, single-arm, multi-surgeon study (NCT #1252862, clinicaltrials.gov) enrolled eyes with OAG, preoperative intraocular pressure (IOP) of 18-30 mmHg on 1 ocular hypotensive medication, and 22-38 mmHg after medication washout. Eyes underwent standalone implantation of 2 iStent devices and were followed through 60 months postoperatively. Efficacy was quantified by mean diurnal IOP and medication usage. Efficacy endpoints included the proportion of eyes with ≥20% IOP reduction versus baseline unmedicated IOP (primary efficacy), and the proportion of eyes with IOP ≤18 mmHg (secondary efficacy) without medication or secondary glaucoma surgery. Safety parameters included visual acuity, cup-to-disc ratio, visual field, and complications and adverse events. RESULTS:< .0001). At Month 60, 89.7% (26/29) of eyes achieved the primary efficacy endpoint of ≥20% IOP reduction versus baseline unmedicated IOP, and 86.2% (25/29) of eyes achieved the secondary efficacy endpoint of IOP ≤18 mmHg, without medication or secondary glaucoma surgery. Throughout follow-up, 89.7-91.3% of eyes were on no medications. Favorable safety included no secondary glaucoma surgeries, minimal adverse events, and stable visual acuity, cup-to-disc ratio, and visual fields through 5 years postoperative. CONCLUSIONS:This prospective interventional study demonstrates persistent 5-year reductions in IOP and freedom from medications, together with favorable safety, following implantation of 2 first-generation trabecular micro-bypass stents in eyes with OAG on 1 preoperative medication.

PURPOSE/OBJECTIVE:To evaluate terpinen-4-ol lid scrubs (Cliradex) with Microblepharoexfoliation (MBE) (BlephEx) in the treatment of Demodex blepharitis. METHODS:An Institutional Review Board (IRB) approved the randomized prospective double-masked trial of 50 patients with Demodex positive blepharitis. All subjects were given an in-office MBE treatment and randomized to masked lid scrubs (terpinen-4-ol or sham) twice daily for 1 month. All subjects then returned for an additional MBE treatment and received open-label terpinen-4-ol scrubs twice daily for 1 month. OUTCOMES/RESULTS:Demodex levels, Ocular Surface Disease Index, tear osmolarity, MMP-9, Schirmer 1 and grading of the lid margin appearance, meibomian gland dropout, and meibomian gland secretions. RESULTS:Forty-six subjects (23 per group) were included for the analysis; 4 lost to follow up. Total Demodex folliculorum levels in the Cliradex group improved: 4.7 to 3.6 (first month interval P = 0.266) to 2.6 (second month interval P = 0.279), overall P < 0.05 over 2 months. Total levels in the sham group improved: 5.1 to 3.0 (first month interval P < 0.05) to 2.5 (second month interval P = 0.496), overall P < 0.05 over 2 months. No clear statistically meaningful improvements in other dry eye and blepharitis data metrics were observed. CONCLUSIONS:In-office MBE treatments combined with either Cliradex terpinen-4-ol medicated lid scrubs or sham scrubs showed a statistically significant reduction in D. folliculorum infestation levels; however, conclusions on clinical significance could not be made. In-office MBE with terpinen-4-ol lid scrubs showed no significant improvement over sham scrubs.

PURPOSE/OBJECTIVE:To evaluate long-term visual and astigmatic outcomes of sequential corneal crosslinking (CXL) followed by topography-guided photorefractive keratectomy (PRK). SETTING/METHODS:Single-practice outpatient setting. DESIGN/METHODS:Retrospective case review. METHODS:This is a single-surgeon retrospective case review of eyes with keratoconus undergoing sequential CXL and then topography-guided PRK. Change in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), topographic, refractive, and keratometric astigmatism was analyzed using power vector analyses at baseline, 6 months, and 12 months after topography-guided PRK. Changes in higher-order aberrations (HOAs), posterior astigmatism, spherical equivalent (SE), and central corneal thickness (CCT) were also analyzed. Correlations between age, time between CXL and PRK, sex, manifest SE, CCT, maximum and average keratometric values, and HOAs were evaluated for significance. RESULTS:Of the 62 eyes studied, regardless of refractive treatment, topography-guided PRK following CXL in patients with keratoconus improved CDVA (mean 20/30; 2-line improvement) and UDVA (mean 20/50; 4-line improvement). Over 12 months, visual acuity continued to improve across all eyes treated (P < .001). Overall, there were significant improvements in corneal astigmatism, maximum keratometry, mean keratometry, SE, posterior astigmatism, and total HOAs. No significant correlations were found between age, sex, time elapsed between CXL and PRK, and age at the time of either procedure on final visual acuity. CONCLUSIONS:Results of this study reinforced previous findings that topography-guided PRK in previously cross-linked keratoconus eyes proves to be an efficacious and safe method for improving visual acuity and reducing irregular corneal astigmatism, with continued improvement.