TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25-73 letters) due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every-16-week dosing regimen was based on central subfield thickness (CST) and BCVA change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE and RHINE (n = 940 and 951, respectively), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimab every 8 weeks (YOSEMITE and RHINE, +10.7 letters and +10.9 letters, respectively) or T&E (+10.7 letters and +10.1 letters, respectively) were comparable with aflibercept every 8 weeks (+11.4 letters and +9.4 letters, respectively). The median number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections, respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% of patients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96. Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without an interval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average: faricimab every 8 weeks -216.0/-202.6 µm, faricimab T&E -204.5/-197.1 µm, aflibercept every 8 weeks -196.3/-185.6 µm), and more patients achieved absence of DME (CST < 325 µm; YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 87%-92%/88%-93%, faricimab T&E 78%-86%/85%-88%, aflibercept every 8 weeks 77%-81%/80%-84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 59%-63%/56%-62%, faricimab T&E 43%-48%/45%-52%, aflibercept every 8 weeks 33%-38%/39%-45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, with a safety profile comparable with that of aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition to promote vascular stability and to provide durable efficacy for patients with DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials.

BACKGROUND: Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). METHODS: TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300). FINDINGS: Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]). INTERPRETATION: Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD. FUNDING: F Hoffmann-La Roche.

Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials.

BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.

Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.

PURPOSE: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD). METHODS: Treatment-naïve patients with nAMD were randomly assigned (1:1) to faricimab 6.0 mg up to every 16 weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0 mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. RESULTS: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n = 61; aflibercept n = 59) and non-Asian country (faricimab n = 604; aflibercept n = 605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved ≥ Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile. CONCLUSION: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03823287 (TENAYA); NCT03823300 (LUCERNE). Date of registration: January 30, 2019.

Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials.

PURPOSE: To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). DESIGN: Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials. PARTICIPANTS: Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n = 32). METHODS: Changes in visual function and imaging/anatomic parameters were evaluated over time using a mixed model for repeated measurement accounting for key baseline characteristics. MAIN OUTCOME MEASURES: Prespecified end points included change in GA area from baseline, best-corrected visual acuity (BCVA) score assessed by Early Treatment Diabetic Retinopathy Study (ETDRS), and visual acuity under low-luminance (LLVA). RESULTS: At 24 months, adjusted mean (standard error) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). Progression of GA was greater in patients with baseline nonsubfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (standard error) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months were -13.88 (1.40) and -7.64 (1.20) in Proxima A, -9.49 (1.29) and -7.57 (1.26) in Proxima B fellow eye CNV cohort, and -11.48 (3.39) and -8.37 (3.02) in Proxima B fellow eye intermediate AMD cohort, respectively. CONCLUSIONS: The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.

Intraocular Pressure Outcomes After Lampalizumab Injections in Patients With Geographic Atrophy.

Importance: Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more recently approved intravitreous agents involve volumes from 0.07 to 0.1 mL. It is not well established whether repeated 0.1-mL intravitreous injections may result in IOP-related complications. Objective: To investigate the effect of 1 year of repeated 0.1-mL intravitreous injections on IOP outcomes. Design, Setting, and Participants: This study was a post hoc analysis of 2 clinical trials investigating the IOP safety of intravitreous lampalizumab on geographic atrophy secondary to age-related macular degeneration. Both trials were conducted between 2014 and 2018 and recruited participants who were 50 years or older and had bilateral geographic atrophy. This post hoc analysis was performed between 2018 and 2022. Interventions: Intravitreous lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks. Main Outcomes and Measures: IOP changes in the 4-week-frequency study arms and ocular adverse events to week 48 in all arms. The hypothesis for this analysis was formulated after data collection. Results: Among a total of 1851 participants, there was no change in mean pre-injection IOP values through 48 weeks in either arm. The adverse events glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm. Conclusions and Relevance: Over 1 year, IOP increases were rare and did not affect treated participants more frequently than sham arm participants. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL. Trial Registration: ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531.

YOSEMITE and RHINE: Phase 3 Randomized Clinical Trials of Faricimab for Diabetic Macular Edema: Study Design and Rationale.

Purpose: Faricimab is a novel anti-angiopoietin-2 and anti-vascular endothelial growth factor (VEGF) bispecific antibody with high affinities and specificities for both VEGF and angiopoietin-2. It is postulated that targeting angiogenic factors and inflammatory pathways in addition to the VEGF pathway will increase treatment durability and improve outcomes. The phase 3 YOSEMITE (ClinicalTrials.gov identifier, NCT03622580) and RHINE (ClinicalTrials.gov identifier, NCT03622593) trials are designed to assess efficacy, safety, and durability of faricimab compared with aflibercept in patients with diabetic macular edema (DME). The trials evaluate a personalized treatment interval (PTI) approach to address heterogeneity in treatment response among patients with DME. Design: Two identically designed, global, double-masked, randomized, controlled phase 3 trials (YOSEMITE and RHINE). Participants: Adults with center-involving DME secondary to type 1 or 2 diabetes mellitus. Methods: These studies were designed to evaluate 3 treatment groups: faricimab 6.0 mg dosed either at fixed dosing every 8 weeks after initial treatment with 6 intravitreal doses at 4-week intervals, or faricimab 6.0 mg dosed according to PTI after initial treatment with 4 every-4-week doses, compared with aflibercept 2.0 mg dosed every 8 weeks after 5 initial every-4-week doses. The primary end point of the studies was change from baseline in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Secondary end points included anatomic, durability, and patient-reported outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. The PTI is a protocol-defined flexible regimen based on the treat-and-extend concept, which allowed up to every-16-week adjustable dosing based on objective and standardized criteria. The PTI design aimed to maximize therapeutic results while minimizing treatment burden. Main Outcome Measures: We describe the rationale for the study design and the novel PTI (up to every-16-week adjustable dosing) approach for treatment with faricimab. Results: YOSEMITE and RHINE enrolled 940 and 951 patients, respectively. Results from each study will be reported separately. Conclusions: YOSEMITE and RHINE were the first registrational trials in retinal disease to incorporate an objective PTI regimen, allowing for up to every-16-week adjustable dosing with a dual angiopoietin-2 and VEGF-A inhibitor, faricimab 6.0 mg, for treatment of DME.

TENAYA and LUCERNE: Rationale and Design for the Phase 3 Clinical Trials of Faricimab for Neovascular Age-Related Macular Degeneration.

Purpose: To describe the design and rationale of the phase 3 TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) trials that aimed to assess efficacy, safety, and durability of faricimab, the first bispecific antibody for intraocular use, which independently binds and neutralizes both angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A) versus aflibercept in patients with neovascular age-related macular degeneration (nAMD). Design: Identical, global, double-masked, randomized, controlled, phase 3 clinical trials. Participants: Adults with treatment-naïve nAMD. Methods: These trials were designed to evaluate patients randomized to receive faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses. The initial doses in the faricimab arm were followed by individualized fixed treatment intervals up to week 60, based on disease activity assessment at weeks 20 and 24, guided by central subfield thickness, best-corrected visual acuity (BCVA), and investigator assessment. The primary efficacy end point was BCVA change from baseline averaged over weeks 40, 44, and 48. Secondary end points included the proportion of patients receiving every-8-week, every-12-week, and every-16-week faricimab and anatomic outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. From week 60, faricimab-treated patients followed a personalized treatment interval (PTI), a novel protocol-driven treat-and-extend regimen with interval adjustment from every 8 weeks to every 16 weeks based on individualized treatment response measured by anatomic criteria, functional criteria, and investigator assessment of patients' disease activity. Main Outcome Measures: Rationale for trial design and PTI approach. Results: The TENAYA and LUCERNE trials were the first registrational trials in nAMD to test fixed dosing regimens up to every 16 weeks based on patients' disease activity in year 1 and incorporate a PTI paradigm during year 2. The PTI approach was designed to tailor treatment intervals to individual patient needs, to reflect clinical practice treatment practice, and to reduce treatment burden. Conclusions: The innovative trial design rationale for the TENAYA and LUCERNE trials included maximizing the benefits of angiopoietin-2 blockade through dosing up to every 16 weeks and PTI regimens based on patients' disease activity while fulfilling health authority requirements for potential registrational efforts.

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.

Microperimetry for geographic atrophy secondary to age-related macular degeneration.

Geographic atrophy (GA) is a progressive, advanced form of age-related macular degeneration leading to visual function impairment and irreversible vision loss. Standard clinical tests to evaluate visual function in patients with GA provide poor anatomic-functional correlation, whereas fundus imaging does not assess the visual function deficit. Microperimetry is a psychophysical visual function test that spatially maps retinal sensitivity and allows for identification of correlation of anatomic features with visual function. In this review, we present an overview of mesopic microperimetry for GA, including commercially available microperimetry devices, strategies to capture a mesopic microperimetry test, and strategies to assess and interpret microperimetry data in patients with GA. We demonstrate the importance of microperimetry data for assessing GA progression and for evaluating visual function loss through anatomic-functional correlations. Although valuable, current microperimetry tests require an extensive time commitment from the patient and examiner, and the development of faster, more reproducible and accessible methods is important to enable broader use of microperimetry in both clinical and research settings.

Management of post-LASIK dry eye: a multicenter randomized comparison of a new multi-ingredient artificial tear to carboxymethylcellulose.

PURPOSE: To compare the efficacy and safety of a preservative-free, multi-ingredient formulation of carboxymethylcellulose 0.5%, hyaluronic acid 0.1%, and organic osmolytes (CMC-HA), to preservative-free carboxymethylcellulose 0.5% (CMC) in the management of postoperative signs and symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK). METHODS: This was a double-masked, randomized, parallel-group study conducted in 14 clinical centers in Canada and Australia. Subjects with no more than mild dry eye instilled CMC-HA or CMC for 90 days post-LASIK. Ocular Surface Disease Index© (OSDI; primary efficacy measure), corneal staining, tear break-up time (TBUT), Schirmer's test, acceptability/tolerability surveys, and visual acuity were assessed at screening and days 2, 10, 30, 60, and 90 post-surgery. Safety analyses included all enrolled. RESULTS: A total of 148 subjects (CMC-HA, n=75; CMC, n=73) were enrolled and assigned to receive treatment, and 126 subjects completed the study without any protocol violations. Post-LASIK, dry eye signs/symptoms peaked at 10 days. OSDI scores for both groups returned to normal with no differences between treatment groups at day 90 (P=0.775). Corneal staining, Schirmer's test, TBUT, and survey results were comparable. Higher mean improvements in uncorrected visual acuity were observed in the CMC-HA group at all study visits, reaching statistical significance at day 30 (P=0.013). Both treatments were well tolerated. CONCLUSION: CMC-HA-containing artificial tears relieved post-LASIK ocular dryness as well as CMC alone, and demonstrated incremental benefit in uncorrected vision, with a favorable safety profile. Results support use of CMC-HA eye drops to reduce signs and symptoms of ocular dryness post-LASIK.

Glaucoma screening using relative afferent pupillary defect.

PURPOSE: To assess the relative afferent pupillary defect (RAPD) by swinging flashlight as a potentially useful screening test for glaucomatous optic neuropathy. METHODS: One hundred seven subjects prospectively recruited from a mixed population of glaucomatous and nonglaucomatous patients were examined for a RAPD by 1 individual masked with regard to disease presence. All subjects underwent a swinging flashlight test with, when necessary, the aid of neutral density filters, to determine whether or not a RAPD was present. A determination of glaucoma diagnosis, as well as classification of disease stage, was subsequently assessed based upon review of history and ophthalmic examination. This clinical information regarding glaucomatous disease was ascertained without knowledge of study RAPD status. The acquisition of such clinical information and performance of swinging flashlight testing for RAPD was conducted by different individuals with the latter being a nonophthalmologist. RESULTS: Statistical analysis demonstrated an odds ratio of 9.71 (95% CI, 3.72-25.40) for glaucomatous disease if a RAPD was present, with a sensitivity of 66.7% and a specificity of 82.9%. Subanalysis of patients who had not previously undergone cataract surgery revealed an odds ratio of 17.05 (95% CI, 4.73-61.44) for glaucomatous disease if a RAPD was present, with a sensitivity of 68.8% and a specificity of 88.6%. CONCLUSIONS: RAPD screening by a swinging flashlight test with neutral density filters was moderately sensitive and strongly specific for glaucoma. Sensitivity, specificity, and predictive value improved when patients who had previously undergone cataract surgery were removed from the analysis.

Axial length does not correlate with degree of visual field loss in myopic Chinese individuals with glaucomatous appearing optic nerves.

PURPOSE: We previously described a group of patients of Chinese ancestry who presented with optic nerve appearance and visual field loss suggestive of glaucoma but did not show progression characteristic of this disease for up to 7 years. The purpose of this study was to assess whether axial length is a risk factor for visual field loss in patients presenting with this cluster of findings. PATIENTS AND METHODS: Twenty patients of Chinese ancestry with characteristics of this previously described condition including myopia, tilted discs, and glaucomatous visual field abnormalities who also had asymmetric visual field loss were enrolled in this study. Patients underwent axial length measurement of both eyes and a fellow eye analysis was performed to determine the relationship between axial length and visual field loss. RESULTS: Tilted discs were found in 30 out of 40 eyes, with cup/disc ratios ranging from 0.5 to 0.9. Myopia >6.00 diopters was also found in 30 out of 40 eyes. In these subjects with disease that was discordant between the 2 eyes, longer axial length was not found to be associated with greater visual field loss (P>0.99, Freeman-Halton extension of the Fisher exact test). No correlation was found between axial length and mean deviation on visual field testing (r=-0.06). CONCLUSIONS: We did not find axial length to be a risk factor for visual field loss in eyes with asymmetric disease in this patient population. These findings suggest that factors other than progressive lengthening of the eye play an important role in the etiology of glaucomatous appearing optic nerve damage and visual field loss in this specific subset of patients.