Methodological Appraisal of Phase 3 Clinical Trials in Geographic Atrophy.

Geographic atrophy (GA) secondary to age-related macular degeneration is a common cause of blindness worldwide. Given the recent approval of the first therapy for GA, pegcetacoplan, we critically appraise methodological aspects of the phase 3 clinical trials published so far in this disease in relation to their design, analysis and interpretation. We reviewed some of the key attributes of all phase 3 clinical trials in GA available in the main public registry of clinical trials as of 20 May 2023. The topics discussed included types of endpoints, eligibility criteria, p-value and effect size, study power and sample size, the intention to treat principle, missing data, consistency of results, efficacy-safety balance and application of results. Five phase 3 clinical trials have reported results, either partially or completely: GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE and GATE. Although there are many similarities between these trials in terms of endpoints or broad eligibility criteria, they differ in several aspects (metric of the primary endpoint, sample size, type of adverse events, etc.) that can influence the results, which are discussed. Readers should understand key methodological aspects of clinical trials to improve their interpretation. On the other hand, authors should adhere to clinical trial reporting guidelines to communicate what was done and how it was done.

Visual disturbances produced after the implantation of 3 EDOF intraocular lenses vs 1 monofocal intraocular lens.

PURPOSE: To compare the visual disturbances experienced by patients receiving 1 of 3 extended depth-of-focus (EDOF) intraocular lenses (IOLs) or a monofocal IOL as the control. SETTING: OMIQ-Recerca Center. Spain. DESIGN: Prospective comparative randomized double-blind study. METHODS: 22 patients were included per group. The IOLs evaluated were the AcrySof IQ Vivity (Vivity group), AT LARA 829MO (AT Lara group), or TECNIS Symfony ZXR00 (Symfony group) and the monofocal AcrySof IQ SN60WF (Monofocal group). The variables analyzed were the light distortion index (LDI), best-fit circle radius (BFC Rad ), and self-reported vision quality with a questionnaire (QoV). Outcomes were evaluated at the 3-month follow-up visit. RESULTS: Under monocular conditions, no differences between groups were detected for the LDI and BFC Rad . Under binocular conditions, significant differences in both variables were produced. The Monofocal group reported better values than Symfony ( P = .025; P = .024) and AT Lara ( P = .002; P = .002) groups. The Vivity group reported better values than Symfony ( P = .015; P = .014) and AT Lara ( P = .001; P = .001) groups. Halos were not reported by 81.8% (18) of patients in the Vivity group, 90.9% (20) of patients in the Monofocal group, 50% (11) of patients in the AT Lara group, and 59% (13) of patients in the Symfony group. CONCLUSIONS: The diffractive EDOF IOL models examined in this study induced similar visual disturbances, which were worse than those produced by the nondiffractive extended-range IOL and the monofocal IOL. The nondiffractive lens and the monofocal lens did not show differences.

Multicountry clinical outcomes of a new nondiffractive presbyopia-correcting IOL.

PURPOSE: To evaluate the effectiveness and safety of a new presbyopia-correcting intraocular lens (IOL) with a nondiffractive design, DFT015, compared with an aspheric monofocal IOL, SN60WF. SETTING: 19 investigational sites in 4 countries: Australia, Canada, Spain, and the United Kingdom. DESIGN: Prospective, randomized, parallel-group, controlled, assessor- and patient-masked clinical study. METHODS: Participants aged ≥22 years with bilateral cataracts were randomized to DFT015 or SN60WF in a 5:4 ratio and masked until final postoperative follow-up at month 6. The primary effectiveness objective was superiority of DFT015 over SN60WF in mean monocular photopic distance-corrected intermediate visual acuity (DCIVA) at month 3. Secondary effectiveness objectives included noninferiority of DFT015 to SN60WF in mean monocular photopic corrected distance visual acuity (CDVA) and superiority in the mean monocular photopic distance-corrected near visual acuity (DCNVA) at month 3. Visual disturbances were assessed at month 6. RESULTS: 282 patients were randomized to DFT015 (n = 159) or SN60WF (n = 123). All effectiveness objectives were achieved at month 3 in first eyes. For monocular photopic results in first eyes, DFT015 demonstrated superior mean DCIVA (least squares means of -0.139 logMAR in favor of DFT015, P < .001), noninferior mean CDVA (97.5% upper confidence limit [UCL] of the difference was <0.1 logMAR) and superior mean DCNVA (95% UCL of the difference was <0.0 logMAR) compared with SN60WF at month 6. DFT015 exhibited a similar visual disturbance profile to that of SN60WF. CONCLUSIONS: DFT015 provided superior intermediate and near vision and a similar visual disturbance profile compared with an aspheric monofocal IOL.

How Do Patients Feel About Visual Field Testing? Analysis of Subjective Perception of Standard Automated Perimetry.

PURPOSE: A high rate of unreliability is an issue in visual field (VF) testing, especially in elderly patients, and warrants patient education. We assessed whether subjective perception of the visual field test (VFT) is a good predictor of its reliability in different age groups and examined age differences in patients' awareness of VF damage. METHODS: This cross-sectional study investigated 107 VFT results of 54 patients with glaucoma or ocular hypertension. Subjective perceptions were compared to reliability indices for cooperation analysis and to mean deviation results for VF damage analysis, and an age-segregated sub-analysis was performed. RESULTS: Kappa coefficients showed poor agreement between subjective and objective parameters. Nevertheless, there were age differences. Younger patients had a higher positive predictive value and sensitivity in cooperation analysis and a higher negative predictive value in VF damage analysis. CONCLUSIONS: Patients' perception of cooperation in VFT is a poor predictor of its reliability. Although young cooperative patients may be aware of their good cooperation, even the youngest are unaware of their poor performance. This emphasizes the importance of giving proper directions to all patients during VFT to obtain better reliability indices. Younger, healthy patients are more aware of their health status, than those with a damaged VF, regardless of age. Therefore, illness education is crucial in all glaucoma patients.

Multicenter visual outcomes comparison of 2 trifocal presbyopia-correcting IOLs: 6-month postoperative results.

PURPOSE: To clinically evaluate visual performance of the AcrySof IQ PanOptix TFNT00 and AT LISA tri 839MP intraocular lenses (IOLs) in binocular visual acuity (VA) and to characterize low-contrast visual performance at 6 months postimplantation. SETTING: Multicenter, 15 sites. DESIGN: Prospective, parallel-group, randomized, double-masked, postmarketing clinical study. METHODS: Binocular uncorrected distance (UDVA, 4 m), intermediate (UIVA, 60 cm), and near (UNVA, 40 cm) visual acuities and binocular defocus curves were evaluated under photopic lighting conditions. Photopic and mesopic contrast sensitivities with and without glare were assessed. RESULTS: The study included 182 subjects (62% women; mean age, 66 ± 9.4 years) who were implanted bilaterally with the TFNT00 IOL (n = 93) or 839MP IOL (n = 89), and binocular VA was evaluated 4 to 6 months (120-180 days) postimplantation. The TFNT00 IOL group showed superior visual outcomes compared with the 839MP IOL group in binocular UIVA (P = .001) and UNVA (P = .003) and noninferior outcomes in UDVA (95% CI, -0.023 to 0.041; upper limit <0.1 logarithm of the minimum angle of resolution [logMAR] [margin of noninferiority]). Mean defocus curve from 0.00 to -3.00 diopter (D) ranged from 0.1 to 0.0 logMAR for both IOLs; better mean VA values (logMAR) were observed in the TFNT00 IOL group between -1.50 and -2.50 D compared with those of the 839MP IOL group. Contrast sensitivity values were similar between the 2 groups in all conditions. CONCLUSIONS: The results of this study showed improved visual performance at near and intermediate distances with the TFNT00 IOL compared with that of the 839MP IOL.

Maximum Medical Therapy: Brinzolamide/Brimonidine And Travoprost/Timolol Fixed-Dose Combinations In Glaucoma And Ocular Hypertension.

INTRODUCTION: Maximal medical therapy (MMT) is the use of ≥3 classes of topical anti-glaucoma agents to achieve maximal intraocular pressure (IOP) reduction while minimizing adverse effects and compliance challenges. PURPOSE: To evaluate the additive IOP-lowering effect of twice-daily brinzolamide 1%/brimonidine 0.2% fixed-dose combination (BBFC) used adjunctively with once daily travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG)/ocular hypertension (OHT). METHODS: In this phase IV, double-masked study, patients on TTFC for ≥28 days, aged ≥18 years, with mean IOP ≥19 and ≤28 mmHg in at least 1 eye were randomized to receive BBFC+TTFC (n=67) or vehicle+TTFC (n=67) for 6 weeks. The primary endpoint was mean change in diurnal IOP from baseline (BL, averaged over 09:00 and 11:00) at Week 6. RESULTS: The study was terminated prematurely due to recruitment challenges. BL mean IOP was similar in both groups (BBFC+TTFC: 21.6±1.78 mmHg; vehicle+TTFC: 21.8±1.90 mmHg). Mean change in diurnal IOP from BL at Week 6 was greater with BBFC+TTFC (-4.25 mmHg, 95% confidence interval [CI]: -4.7, -3.8) than with vehicle+TTFC (-2.11 mmHg, 95% CI: -2.6, -1.6, treatment difference, -2.15 mmHg (95% CI: -2.8, -1.5; P<0.001). Ocular adverse events (AEs) were reported in 11.9% of patients given BBFC+TTFC and 7.5% of patients given vehicle+TTFC. The AE with highest frequency was punctate keratitis (3%) in the BBFC+TTFC group; eye irritation (3%) in the vehicle+TTFC group. CONCLUSION: BBFC+TTFC as MMT demonstrated clinically relevant and statistically significant reductions in mean diurnal IOP in patients with OAG/OHT. AEs were consistent with known safety profiles of individual medications.

Posterior Hyaloid Dissection: Let's Make It Easy with Blue.

PURPOSE: Our aim is to present in this online supplementa ry video (see www.karger.com/doi/10.1159/000486348) an easy new surgical technique using blue dye to dissect the posterior hyaloid when performing pars plana vitrectomy. PROCEDURES: Dual-Blue stain is injected in vitreous cavity just after central vitrectomy is performed. The distribution of the blue stain will allow us to know if there is a posterior vitreous detachment or not ("blue lake fashion" or "blue jelly fashion," respectively) and as an excellent visualization of the vitreous fibers is accomplished, dissection of the posterior hyaloid can be performed without difficulty. RESULTS: This procedure allows a much more simple, fast, and safe dissection of posterior hyaloid even for an inexperienced vitreoretinal surgeon. The cleavage plane between the retina and the posterior hyaloid is easily differentiated. CONCLUSIONS: A more controlled and easy dissection of posterior hyaloid during vitrectomy is accomplished with this simple technique without adding any extra cost. Message of the paper: An easy technique that allows a much easier dissection of the posterior hyaloid during vitrectomy improving visualization and decreasing risks. No extra cost, nor time is needed.