Private equity ownership of ophthalmology practices: how does it impact clinical research?

PURPOSE OF REVIEW: To explore the impact of private equity ownership of ophthalmology practices on the success of their clinical research programs. RECENT FINDINGS: Private equity partnership in the clinical research space has been steadily occurring over the past decades. In addition to contract research organizations, private equity groups have also consolidated multiple independent clinical research networks. By investing in an increasing number of retina practices, one private equity group is attempting to create a synergistic relationship between clinical practice and clinical research with the goal of supporting a larger, more robust clinical research network. SUMMARY: Although there are physician concerns about the potential deleterious effects of private equity ownership on clinical research capabilities, private equity support has the potential to be an important stimulus for clinical research growth. VIDEO ABSTRACT: http://links.lww.com/COOP/A48.

Patient Preference and Treatment Satisfaction With a Port Delivery System for Ranibizumab vs Intravitreal Injections in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Importance: The port delivery system (PDS) with ranibizumab has demonstrated noninferior and equivalent efficacy compared with monthly intravitreal injections of ranibizumab, an anti-vascular endothelial growth factor (VEGF) agent, in patients with neovascular age-related macular degeneration (nAMD), but evaluating patient preference is important to help inform clinical decision-making. Objective: Evaluate treatment satisfaction for ranibizumab delivered via PDS vs intravitreal injections as well as patient preference among those assigned to PDS. Design, Setting, and Participants: Archway was a phase 3 randomized active-comparator open-label clinical trial conducted at 78 sites in the US. Patients 50 years and older with nAMD diagnosed within 9 months of screening with a documented response to anti-VEGF therapy were included. Of 619 patients screened, 418 were enrolled; 415 were included in the primary analysis and 234 were included in the secondary exploratory analysis. The Archway study ran from September 12, 2019, through primary readout on May 22, 2020. Interventions: Patients were randomized 3:2 to PDS with ranibizumab, 100 mg/mL, with fixed refill exchanges every 24 weeks or intravitreal ranibizumab injections, 0.5 mg, every 4 weeks. Main Outcomes and Measures: Treatment satisfaction was measured using the Macular Disease Treatment Satisfaction Questionnaire in the PDS and intravitreal injection arms at week 40. Patient preference was assessed using the content-validated PDS Patient Preference Questionnaire (PPPQ), which measured the proportion of patients in the PDS arm with monthly monitoring who preferred treatment with the PDS at week 40 over previous intravitreal injections or concurrent fellow-eye injections. Both outcomes were exploratory end points. Results: The mean (SD) age of participants at baseline was 75.0 (7.9) years; 234 participants (59%) were women and 162 (41%) were men. At week 40, differences in overall treatment satisfaction scores were minimal for the PDS and intravitreal injection arms (mean, 68.0; 95% CI, 67.4-68.6; n = 237 and mean, 66.1; 95% CI, 64.9-67.3; n = 159, respectively; difference, 1.9; 95% CI, 0.7-3.1). A total of 234 of 248 patients (94.4%) in the PDS arm were included in the PPPQ analysis. At week 40, almost all patients in the PDS arm preferred treatment via PDS (218 of 234 [93.2%]) vs previous intravitreal injections (3 of 234 [1.3%]), including 172 of 234 (73.5%) with a very strong preference for the PDS. In patients who received concurrent fellow-eye injections (n = 78), 72 (92.3%) preferred the PDS. Conclusions and Relevance: Although PDS treatment was preferred by almost all patients assigned to PDS over previous intravitreal injections, both delivery methods have high treatment satisfaction. These findings provide further evidence for the PDS as a meaningful alternative treatment option for patients with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT03677934.

Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.

PURPOSE: To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Phase 3, open-label, randomized, visual acuity assessor-masked noninferiority and equivalence trial. PARTICIPANTS: Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy. METHODS: Patients were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/ml with fixed 24-week (Q24W) refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5-mg injections every 4 weeks (monthly ranibizumab). MAIN OUTCOME MEASURES: Primary end point was change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter (letters) score from baseline averaged over weeks 36 and 40 (noninferiority margin,-4.5 letters; equivalence margin, ±4.5 letters). RESULTS: Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with the PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 letters (PDS Q24W arm) and 75.5 letters (monthly ranibizumab arm; Snellen equivalent, 20/32). Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 letters (standard error [SE], 0.5 letters) in the PDS Q24W arm and +0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, -0.3 letters; 95% confidence interval, -1.7 to 1.1 letters). PDS Q24W was both noninferior and equivalent to monthly ranibizumab. Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure. Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. Most ocular adverse events in the PDS Q24W arm occurred within 1 month of implantation. CONCLUSIONS: Archway met its primary objective and PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab, with 98.4% of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.

Prospective one-year study of ranibizumab for predominantly hemorrhagic choroidal neovascular lesions in age-related macular degeneration.

PURPOSE: To determine the safety and effect of ranibizumab on predominantly hemorrhagic choroidal neovascular lesions due to age-related macular degeneration. METHODS: Seven subjects with predominantly hemorrhagic choroidal neovascular lesions were treated with intravitreal injections of ranibizumab at baseline, Month 1, and Month 2. Additional monthly injections were given through Month 11 at the discretion of the examiner for a potential maximum of 12 injections. RESULTS: At 12 months, the median visual acuity letter score was 30 (Snellen equivalent: 20/250), with a median change from baseline to last follow-up of +7 letters. Three of 7 subjects (43%) gained 2 or more lines of vision, while no subject lost 2 or more lines. The median change in OCT central subfield thickness from baseline to Month 12 was -109 microm, with a mean of -120 +/- 158 microm. Two eyes had retinal pigment epithelial tears. No ocular adverse events or systemic adverse events were reported related to the usage of ranibizumab. CONCLUSION: With no subject losing 2 or more lines of visual acuity over 12 months and no new safety concerns identified, these predominantly hemorrhagic lesions treated with ranibizumab appeared to have a better visual acuity outcome than the natural history controls of the submacular surgery trials. While the study is limited by few cases enrolled, the results suggest that ranibizumab is able to penetrate through the subretinal hemorrhage to affect the underlying hemorrhagic choroidal neovascular lesion and the natural history.

Racial differences and other risk factors for incidence and progression of age-related macular degeneration: Salisbury Eye Evaluation (SEE) Project.

PURPOSE: To evaluate risk factors for the incidence and progression of age-related macular degeneration (AMD) in a racially heterogeneous, geriatric population. METHODS: Subjects (n = 2240) aged 65 to 84 years underwent 2 examinations separated by 2 years, of which 1937 subjects (85%) were included in this report. Fundus photographs were performed at each examination and were graded by trained readers. Multivariate logistic regression models adjusted for age, sex, race, and clustering between eyes were used to evaluate risk factors for AMD incidence and progression. RESULTS: Smoking was a strong, dose-dependent, risk factor for progression from medium size drusen to large drusen or pigmentary abnormalities within the central 1500-microm macular zone. Smoking was also a strong risk factor for development of incident focal pigmentation within 3000 microm of the foveal center. White participants were significantly more likely than blacks to develop large drusen and focal pigmentation and to progress from medium- to large-sized drusen or pigment abnormalities within the central 1500 microm macular zone. However, whites did not have an increased risk of progression from large drusen or pigment abnormalities within the central 1500-microm perimacular zone to foveal GA or CNV when compared with blacks. CONCLUSIONS: Smoking and race are important risk factors for progression from medium to large drusen or to pigment abnormalities within the central 1500-microm macular zone. Limitations in the power of this study preclude assessment of the roles of smoking and race on the ultimate progression to foveal GA or CNV once central large drusen or pigment abnormalities are present.

The surgical management of cataract: barriers, best practices and outcomes.

Cataract is the leading cause of blindness in the world. Cataract surgery has been shown by multiple studies to be one of the most cost-effective health interventions, and leads to a dramatic increase in quality of life and productivity for many patients. Though there has been marked improvement in the last several decades, surgical delivery services in developing nations are still suboptimal, and a large backlog in cataract cases continues to grow. To decrease this backlog, barriers to surgery, such as direct and indirect patient costs, geographic access to surgical facilities and surgeons, cultural factors, and patient education, must be addressed. In particular, access to services by women and rural patients needs to be improved. It is clear that extracapsular techniques are cost-effective and lead to better post-operative outcomes than intracapsular cataract extraction with aphakic correction. In addition, monitoring surgical outcomes is essential for improving the quality of surgical services. However, other issues regarding the delivery of cataract surgical services, including the role of average power intraocular lenses and the role of non-physician surgeons, are yet unresolved. Information about the true cost of surgery, including costs of surgeon training, equipment, and patient outreach programs, is needed so that the goal of self-sustaining programs may be obtained.

Patients' preferences in choosing therapy for retinal vein occlusions.

PURPOSE: The purpose of this study was to assess preference values for vein occlusions with macular edema and to determine how this may affect patient perceptions of potential treatments. METHODS: The Submacular Surgery Trials Vision Preference Value Scale and questions regarding enthusiasm for potential treatments were administered to 153 patients with vein occlusion. Univariate analyses identified predictors of preference values, followed by adjustment for potential confounders using multivariate linear regression. Relationships between preference values and enthusiasm for potential treatments were assessed. RESULTS: The mean preference values +/- SD were similar for patients with branch vein occlusions and central vein occlusions (0.65 +/- 0.20). Lower preference values were associated with duration of occlusion of >2 years (P=0.03) and poorer last-recorded visual acuity (P=0.02). Approximately one half of patients were moderately or very enthusiastic about undergoing intravitreal injection. Sixty-nine percent of branch vein occlusion patients were moderately or very enthusiastic about the standard of care, laser photocoagulation; only one third of central vein occlusion patients were moderately or very enthusiastic about standard observation. CONCLUSIONS: These data suggest that vein occlusion with macular edema has a significant impact on quality of life. Most patients were willing to undergo potentially invasive treatment.

Infections following laser in situ keratomileusis: an integration of the published literature.

Infections occurring after laser in situ keratomileusis (LASIK) surgery are uncommon, but the number of reports have steadily increased in recent years. This systematic, comprehensive review and analysis of the published literature has been performed in order to develop an integrative perspective on these infections. We have stratified the data by potential associations, microbiology, treatment, and the degree of visual loss, using Fisher's exact tests and Student's t-tests for analysis. In this review, we found that Gram-positive bacteria and mycobacterium were the most common causative organisms. Type of postoperative antibiotic and steroid use was not associated with particular infecting organisms or severity of visual loss. Gram-positive infections were more likely to present less than 7 days after LASIK, and they were associated with pain, discharge, epithelial defects, and anterior chamber reactions. Fungal infections were associated with redness and tearing on presentation. Mycobacterial infections were more likely to present 10 or more days after LASIK surgery. Moderate or severe visual reductions in visual acuity occurred in 49.4% of eyes. Severe reductions in visual acuity were significantly more associated with fungal infections. Flap lift and repositioning preformed within 3 days of symptom onset may be associated with better visual outcome.

Total anterior corneal surface and epithelial stem cell harvesting: current microkeratomes and beyond.

Currently, most corneal lamellar allografts are performed by manually dissecting donor corneoscleral material for transplantation. Manual dissection is technically challenging and time intensive, and excessive handling of tissue may decrease the likelihood of obtaining viable grafts. These mechanical factors, along with problems controlling immune rejection, have prevented limbal stem cell lamellar allografts in particular from becoming more widely used. Anterior lamellar keratoplasty is gaining in clinical importance and usage but is still only practiced by a limited number of surgeons. Recently, new mechanical and femtosecond laser microkeratomes have been adapted to harvest the anterior corneal surface, including the limbal stem cell region. Preliminary results have been encouraging and give hope that this technique may prove to be of benefit to patients in the future.

Corneal edema resolution after "descemetorhexis".

A 79-year-old woman had left eye phacoemulsification complicated by inadvertent excision of Descemet's membrane (DM). One day postoperatively, the visual acuity was counting fingers with diffuse corneal edema. The patient was treated medically, with gradual resolution of the corneal edema over a 6-month period. The torn edge of DM could be visualized as the edema cleared, and no endothelial cell count could be obtained centrally. Approximately 1 year postoperatively, the central endothelial cell count was 2114 cells/mm(2) in the right eye and 827 cells/mm(2) in the left eye. The decreased cell count, increased polymegethism, and pleomorphism suggested that endothelial cells migrated to cover the stromal surface area in the absence of DM.

Outcome of phacoemulsification after pars plana vitrectomy.

PURPOSE: To compare the outcome of phacoemulsification surgery in patients with and without prior vitrectomy, adjusted for confounding factors. DESIGN: Retrospective cohort study. PARTICIPANTS AND CONTROLS: Thirty-one consecutive eyes undergoing phacoemulsification after pars plana vitrectomy (PPV) and 116 consecutive eyes undergoing phacoemulsification without previous PPV. METHODS: Office records of the operating surgeons were reviewed for age, gender, type of cataract, vitrectomy status, best-corrected visual acuity (BCVA) before and after phacoemulsification, intraoperative difficulties, and postoperative complications. Bivariate analyses between these predictors and the main outcome, BCVA of 20/40 or better after phacoemulsification, were performed using Pearson's chi-square tests. An adjusted analysis of the relationship between outcome and vitrectomy status was performed with logistic regression. Pearson's chi-square tests were used to compare type of cataract, intraoperative difficulties, and postoperative complications in study and control eyes. MAIN OUTCOME MEASURES: BCVA of 20/40 or better after phacoemulsification, rates of intraoperative difficulties, and postoperative complications. RESULTS: The most common indication for PPV was macular hole. The average interval from PPV to phacoemulsification was 15.4 months. Study eyes were followed for an average of 10 months compared with 6.6 months for controls. Study eyes were more likely than controls to have predominantly nuclear sclerotic cataracts (P = 0.002). After cataract extraction, 24 of 31 study eyes (77.4%) and 110 of 116 control eyes (94.8%), had BCVAs of 20/40 or better. After adjusting for confounders, eyes without previous vitrectomy were 3.44 times more likely to obtain a BCVA of 20/40 or better than eyes with prior PPV, but this difference was not statistically significant (95% CI, 0.72-16.67). Only 3 of 31 (9.7%) study and 11 of 116 (9.4%) control eyes had intraoperative difficulties (P = 0.47). Posterior capsule plaque was the most common intraoperative difficulty in study eyes; small pupil requiring stretching or iris hooks was most common in controls. Only 1 of 31 (3.2%) study eyes had a postoperative complication other than posterior capsule opacification compared with 18 of 116 (15.5%) controls (P = 0.07). CONCLUSIONS: A large proportion of patients with prior PPV obtain good visual acuity after phacoemulsification. We did not find significantly higher rates of intraoperative difficulties or postoperative complications compared with controls. The benefits of phacoemulsification seem to be limited only by retinal comorbidity.