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.

IMPACT OF RETINAL FLUID-FREE MONTHS ON OUTCOMES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Treatment Agnostic Analysis of the HAWK and HARRIER Studies.

PURPOSE: To assess the effect of the total number of fluid-free months after loading on visual and anatomical outcomes in neovascular age-related macular degeneration patients receiving anti-vascular endothelial growth factor therapy. METHODS: This post hoc analysis pooled patient-level data from the brolucizumab 6 mg (n = 718) and aflibercept 2 mg (n = 715) arms of the HAWK and HARRIER randomized clinical trials. Based on data from Weeks 12 to 96, patients were assigned to one of five categories based on fluid-free visits (FFVs; the total number of monthly visits at which they were observed to be without retinal fluid). Three definitions of "fluid-free" were explored based on the location of the fluid observed. RESULTS: Patients allocated to Categories 4 (15-21 FFV) and 5 (22 FFV, always dry) consistently had the best visual and anatomical outcomes at Week 96, whereas patients allocated to Categories 1 (0 FFV, never dry) and 2 (1-7 FFV) consistently had the worst visual and anatomical outcomes. Variability in retinal thickness over time was lowest in Categories 4 and 5. CONCLUSION: Absence of retinal fluid at more visits after loading has a positive association with visual and anatomic outcomes in neovascular age-related macular degeneration patients, regardless of fluid type.

Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD.

PURPOSE: To describe the adverse events associated with brolucizumab, in particular the sequence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or retinal vascular occlusion (RO). METHODS: This was an unmasked post hoc analysis of the randomized HAWK/HARRIER clinical trials. Patients with neovascular AMD in the brolucizumab arms of the trials were included. IOI-related adverse events reported by study investigators were analyzed to determine early signs and the time course of IOI-related adverse events, using a subgroup of patients with definite/probable IOI cases identified in an independent unmasked post hoc review by an external safety review committee. A limited literature review on IOI following anti-VEGF therapy was also conducted. RESULTS: Among 50 patients with definite/probable IOI cases identified by the safety review committee, 12 had RV or RO adverse events reported by the investigators. For 6 of 12, IOI (other than RV) was reported before RV or RO. The duration from the first IOI adverse event to the first RV or RO adverse event ranged from 16 to 171 days for 5 patients and was 553 days for 1 patient. Four of the 6 patients received ≥ 1 brolucizumab injection on or after the date of the first IOI adverse event and before the first RV or RO adverse event. CONCLUSIONS: IOI may precede RV or RO in some patients treated with brolucizumab.

RANIBIZUMAB TREATMENT IN TREATMENT-NAIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Results From LUMINOUS, a Global Real-World Study.

PURPOSE: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in treatment-naive patients with neovascular age-related macular degeneration enrolled in LUMINOUS study. METHODS: This 5-year, prospective, multicenter, observational study recruited 30,138 adult patients (treatment-naive or previously treated with ranibizumab or other ocular treatments) who were treated according to the local ranibizumab label. RESULTS: Six thousand two hundred and forty-one treatment-naive neovascular age-related macular degeneration patients were recruited. Baseline (BL) demographics were, mean (SD) age 75.0 (10.2) years, 54.9% females, and 66.5% Caucasian. The mean (SD) visual acuity (VA; letters) gain at 1 year was 3.1 (16.51) (n = 3,379; BLVA, 51.9 letters [Snellen: 20/92]) with a mean (SD) of 5.0 (2.7) injections and 8.8 (3.3) monitoring visits. Presented by injection frequencies <3 (n = 537), 3 to 6 (n = 1,924), and >6 (n = 918), visual acuity gains were 1.6 (14.93), 3.3 (16.57), and 3.7 (17.21) letters, respectively. Stratified by BLVA <23 (n = 382), 23 to <39 (n = 559), 39 to <60 (n = 929), 60 to <74 (n = 994), and ≥74 (n = 515), visual acuity change was 12.6 (20.63), 6.7 (17.88), 3.6 (16.41), 0.3 (13.83), and -3.0 (11.82) letters, respectively. The incidence of ocular/nonocular adverse events was 8.2%/12.8% and serious adverse events were 0.9%/7.4%, respectively. CONCLUSION: These results demonstrate the effectiveness and safety of ranibizumab in treatment-naive neovascular age-related macular degeneration patients.

Optimization of Diabetic Macular Edema Management in the Real World: A Model of Excellence in Retina Units: The EMUREX Initiative.

PURPOSE: To define and develop a model of excellence for the clinical management of diabetic macular edema (DME) patients in a real-world setting. METHODS: A multidisciplinary joint commission (5 ophthalmologists, 1 nurse, and 1 pharmaceutic) established a series of preliminary recommendations based on clinical guidelines and DME activity results from 8 Pilot Hospitals (PH). These were validated by members of each PH and a group of DME patients in discussion workshops. Thus, the validated guideline (VG) took into consideration different aspects, namely, main core points (ranging 0-100), criteria, and indicators. Finally, each PH own setting was compared to the VG in order to settle down a starting point to clinical excellence. RESULTS: Mean PH score was 51.5 (range 30-65). As compared to their maximum, main points that showed best scores were Clinical Guidelines and Protocols (78%) and Portfolio of Services (73%). Topics reaching close to 50% scoring included Resources (55%), Innovation (54%), Care Process (53%), Organization (52%), and Leadership (50%). Lowest scores were observed in the Strategic Alliances (46%) and Staff (37%) points. CONCLUSIONS: Analysis of each PH by the VG delivered a global vision of the starting situation, especially focused in the identification of the different improvement areas. In order to further extend this model into the Public Health System, the effect of implementing it in different hospitals should be assessed to analyze its impact on daily clinical practice and health economics.

FUNCTIONAL AND ANATOMICAL SIGNIFICANCE OF THE ECTOPIC INNER FOVEAL LAYERS IN EYES WITH IDIOPATHIC EPIRETINAL MEMBRANES: Surgical Results at 12 Months.

PURPOSE: To describe the functional and anatomical outcomes of pars plana vitrectomy with epiretinal membrane and internal limiting membrane peel in eyes with and without ectopic inner foveal layers (EIFLs). METHODS: In this retrospective multicenter study, patients diagnosed with idiopathic epiretinal membranes who underwent pars plana vitrectomy with epiretinal membrane and internal limiting membrane peel were enrolled, with a minimum follow-up of 12 months. Preoperative and postoperative spectral domain optical coherence tomography scans were qualitatively and quantitatively evaluated. The association of the EIFL and other spectral domain optical coherence tomography parameters with preoperative and postoperative best-corrected visual acuity (BCVA) was analyzed. RESULTS: One hundred eleven eyes of 107 patients were included. Preoperatively, the EIFLs were present in 56 of 111 eyes (50.4%). The presence of EIFL was significantly associated with lower preoperative and postoperative BCVA (P < 0.001). Ectopic inner foveal layer thickness was negatively correlated with preoperative BCVA (r = 0.58, P < 0.001). Postoperatively, the EIFL persisted in 51 of 56 eyes (91%) with Stage 3 and 4 epiretinal membranes. Ectopic inner foveal layer thickness decreased significantly after surgery (P < 0.001), but postoperative EIFL thinning had no direct effect on postoperative change in BCVA. At 12 months from surgery, EIFL thickness maintained a significant negative correlation with BCVA (r = 0.55, P < 0.001). CONCLUSION: The presence of EIFL should be considered a negative prognostic factor for postoperative anatomical and functional recovery.

PARS PLANA VITRECTOMY FOR THE TREATMENT OF TRACTIONAL AND DEGENERATIVE LAMELLAR MACULAR HOLES: Functional and Anatomical Results.

PURPOSE: Functional and anatomical outcomes of vitrectomy with membrane peeling were compared in tractional lamellar macular holes (LMH)/macular pseudoholes (MPH) versus degenerative LMH. METHODS: This multicenter retrospective study enrolled patients with a minimum follow-up of 6 months. The association of spectral domain optical coherence tomography parameters with preoperative and postoperative best-corrected visual acuity was analyzed. RESULTS: Seventy-seven (74.8%) tractional LMH/MPH and 26 (25.2%) degenerative LMH were included. Preoperative best-corrected visual acuity was better in tractional LMH/MPH (0.39 ± 0.2 logarithm of the minimal angle of resolution, 20/50 Snellen equivalent) than degenerative LMH (0.56 ± 0.2 logarithm of the minimal angle of resolution, 20/66 Snellen equivalent; P < 0.001). Premacular membranes were found in all tractional LMH/MPH, whereas LMH-associated epiretinal proliferation (LHEP) was present in all degenerative LMH. Primary anatomical success was achieved in 97/103 eyes (94.2%), with foveal restoration occurring earlier in degenerative LMH (1.6 ± 2.3 vs. 3.3 ± 3.6 months; P = 0.025). Best-corrected visual acuity improved in both tractional LMH/MPH and degenerative LMH (P < 0.001 and P = 0.012, respectively) but was better in tractional LMH/MPH (P = 0.001). CONCLUSION: The presence of premacular membranes and absence of LMH-associated epiretinal proliferation in all tractional LMH/MPH further distinguishes this from degenerative LMH. Best-corrected visual acuity improved in both subgroups but more so in tractional LMH/MPH. Complete anatomical restoration of foveal microanatomy was rare in degenerative LMH, reflecting significant morphological and pathophysiological differences between the two lesions.

PREOPERATIVE VITREORETINAL INTERFACE ABNORMALITIES ON SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY AS RISK FACTOR FOR PSEUDOPHAKIC CYSTOID MACULAR EDEMA AFTER PHACOEMULSIFICATION.

PURPOSE: We assessed the role of vitreoretinal interface status in the development of pseudophakic cystoid macular edema (PCME) after cataract surgery. METHODS: Prospective cohort study in which 112 patients (112 eyes) scheduled for cataract surgery were selected at random to undergo spectral domain optical coherence tomography (OCT) within 1 week preoperatively and at 1 and 3 months postoperatively. Spectral domain OCT macular images included no vitreoretinal contact, focal and diffuse vitreomacular adhesion, focal and diffuse vitreomacular traction, epiretinal membrane, macular hole, and macular edema. RESULTS: The incidence of PCME was 11.6% (13 eyes), all of them being diagnosed at 1 month, and 7 eyes resolved at 3 months. The only risk factor for PCME was detection of nonsurgical epiretinal membrane by spectral domain OCT before phacoemulsification, being developed in 5 of 16 eyes (χ = 0.08, odds ratio 4.53, 95% confidence interval 1.28-16.13). Other variables such as posterior vitreous detachment, subfoveal choroidal thickness, diabetes, or hypertension were not significantly associated with PCME. CONCLUSION: In this cohort, preoperative detection of epiretinal membrane by spectral domain OCT was a risk factor for PCME after cataract extraction. It is recommended to perform a spectral domain OCT before cataract surgery because the presence of an epiretinal membrane may be passed unnoticed by fundus examination.

Clinical Decision-Making when Treating Diabetic Macular Edema Patients with Dexamethasone Intravitreal Implants.

Diabetes mellitus (DM) is a metabolic disease frequently associated with comorbidities that include diabetic macular edema (DME). The current medical approach to treating DME involves intravitreal injections with either anti-vascular endothelial growth factors or steroids. However, the burden associated with intravitreal injections and DM-derived complications is high, underlining the need to find optimal treatment regimens. In this article we describe the considerations we apply when treating DME patients with dexamethasone intravitreal implants (Ozurdex®), particularly those that influence the clinical decision-making process during the follow-up period. These considerations are based both on the available medical literature and on our clinical experience following the use of these implants in this type of patient, the goal being to optimize the number of injections and the clinical outcome of this therapy. We also provide a general overview of the pathophysiology of DME, highlighting the inflammatory component as a rationale to use steroids in these patients.

ANATOMICAL AND FUNCTIONAL OUTCOMES OF SYMPTOMATIC IDIOPATHIC VITREOMACULAR TRACTION: A Natural History Study From the Pan American Collaborative Retina Study Group.

PURPOSE: To describe the natural history of eyes with symptomatic idiopathic vitreomacular traction (VMT). METHODS: Retrospective multicenter study of 168 eyes with spectral-domain optical coherence tomography (SD-OCT) findings consistent with idiopathic VMT. All eyes were graded according to SD-OCT findings. Grade 1 was defined as incomplete cortical vitreous separation with foveal attachment. Grade 2 was defined as Grade 1 plus intraretinal cysts or clefts. Grade 3 was defined as Grade 2 plus a foveal detachment. All patients were followed for at least 6 months. RESULTS: There were 168 patients (51 men) with a mean age of 68.8 ± 10.7 years. Patients were followed for a mean of 22.7 ± 20.1 months. The mean duration of symptoms before the initial presentation was 3.65 ± 5.42 months. At baseline, 72 eyes had Grade 1, 74 eyes had Grade 2, and 22 eyes had Grade 3 SD-OCT findings. Over the follow-up period, 36 eyes (21.4%) had spontaneous resolution of the VMT with normalization of the foveal anatomy. The mean time to resolution was 12.3 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of the eyes, with 6 eyes developing a lamellar macular hole and 7 eyes developing a full-thickness macular hole. This occurred at a mean of 10.3 ± 10.7 months after the presentation. Subgroup analysis based on baseline SD-OCT grade showed that 4.1% (3 of 73) of Grade 1 eyes compared with 6.8% (5 of 74) of Grade 2 eyes, and 23.8% (5 of 21) of Grade 3 eyes developed a full-thickness macular hole or lamellar macular hole (P = 0.0109, chi-square test). In the remaining 119 eyes, at the last follow-up, 65 eyes had Grade 1, 42 eyes had Grade 2, and 12 eyes had Grade 3 VMT. On average, the best-corrected visual acuity improved from 0.40 ± 0.35 logarithm of the minimum angle of resolution (Snellen, 20/50) at baseline to 0.35 ± 0.36 logarithm of the minimum angle of resolution (Snellen, 20/45; P = 0.0372), and the mean central macular thickness improved from 350 ± 132 µm to 323 ± 121 µm. CONCLUSION: Spontaneous resolution of VMT occurred in 21.4% (36 of 168) of eyes after a mean follow-up of 11.4 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of eyes. The baseline SD-OCT grade may predict the progression to full-thickness macular hole.

Current state of therapeutic strategies with ranibizumab in neovascular age-related macular degeneration.

PURPOSE OF REVIEW: To summarize the current dosing strategies in the management of neovascular age-related macular degeneration with intravitreal injections of ranibizumab. RECENT FINDINGS: A variety of therapeutic strategies has been recently described as an alternative to the monthly fixed treatment. The efficacy and local and systemic safety results of each approach is relevant in order to make a clinical decision and to provide patients an accurate information. SUMMARY: The proposed therapeutic strategies achieve positive visual outcomes when compared with monthly fixed regimen in the clinical trials. However, the real-life practice does not reflect these results. The main cause of this difference is the incapability to adopt any of the different strategies as the clinics are completely booked and this turns into a delay in the diagnostic and treatment visits.

LONG-TERM OUTCOMES OF 23-GAUGE PARS PLANA VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING AND GAS TAMPONADE FOR MYOPIC TRACTION MACULOPATHY: A Prospective Study.

PURPOSE: To investigate the long-term safety and efficacy of microincisional 23-gauge pars plana vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade in the treatment of myopic traction maculopathy. METHODS: A prospective nonrandomized multicenter study was designed. Patients with myopic traction maculopathy without macular hole and retinal detachment were included in the study between January 2009 and May 2012. All patients underwent microincisional 23-gauge pars plana vitrectomy with ILM peeling and 12% C3F8 gas tamponade. In all cases, brilliant blue G staining of the ILM was performed. All patients were prospectively evaluated. The evolution of best-corrected visual acuity (BCVA) and macular thickness were recorded. RESULTS: Myopic traction maculopathy resolved in 28 of the 30 patients (93%) included. Mean follow-up was 33.8 ± 13 months (range, 24-60 months). Mean time of myopic traction maculopathy resolution after surgery was 2.65 ± 1.4 months. At 1 month after surgery, one patient developed a macular hole and another one a rhegmatogenous retinal detachment. After 2 years, another patient developed a retinal detachment. Statistically significant improvements in macular thickness compared with baseline were found at all follow-up visits (P < 0.001, Student's t-test). At final visit, BCVA improved significantly compared with baseline (P = 0.044, Wilcoxon's test). However, a statistically significant improvement in visual acuity was achieved only in eyes with a preoperative Snellen visual acuity ≥ 20/63 (P = 0.027). In contrast, the final BCVA of eyes with worse preoperative visual acuity (<20/63) did not improve significantly (P = 0.41, Wilcoxon's test). CONCLUSION: Microincisional 23-gauge pars plana vitrectomy with ILM peeling and gas tamponade is effective in the treatment of myopic traction maculopathy, with low postoperative complications. Globally, both BCVA and macular thickness improved significantly during the follow-up period. However, greater visual acuity improvements were only seen in eyes with preoperative BCVA equal to or better than 20/63 Snellen equivalent. Some concerns remain about the risk of macular hole formation after ILM peeling. Further studies are necessary to investigate this issue.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO PATHOLOGIC MYOPIA: SIX YEARS OUTCOME.

PURPOSE: To report the visual outcome after 6-year follow-up in highly myopic eyes with choroidal neovascularization treated with anti-vascular endothelial growth factor drugs. METHODS: Retrospective, nonrandomized, multicenter, consecutive, and interventional case series. RESULTS: Seventy-eight patients were treated with intravitreal bevacizumab and 19 with ranibizumab. Mean age of the patients was 56.5 years (SD, 13.3). The average number of letters read was 56.7 (SD, 19.0) at baseline; 65.7 (SD, 18.4) at 12 months; 63.6 (SD, 20.6) at 24 months; 62.4 (SD, 21.4) at 36 months; 60.6 (SD, 22.0) at 48 months; 58.9 (SD, 22.9) at 60 months, and 58.4 (SD, 22.7) at 72 months (P < 0.01, between initial vs. 12, 24, and 36 months; P = 0.07, 0.3, and 0.5 between initial vs. 48, 60, and 72 months, respectively; Student's t-test paired data). The mean total number of intravitreal injections was 3.3 (SD, 2.3; range, 1-9). CONCLUSION: Bevacizumab and ranibizumab are effective therapies and show similar clinical effects in myopic eyes with choroidal neovascularization. Visual acuity gain is maintained at a 3-year follow-up. The improvement is no longer statistically significant at Years 4, 5, and 6.

Intraocular pressure elevation after uncomplicated pars plana vitrectomy: results of the Pan American Collaborative Retina Study Group.

PURPOSE: To compare the incident rates of sustained elevation of intraocular pressure (IOP) after uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane and the unoperated fellow eye. METHODS: Retrospective multicenter study of 198 patients who underwent pars plana vitrectomy for an idiopathic epiretinal membrane that was followed for at least 12 months. The diagnosis of sustained IOP elevation was defined as an elevation of IOP ≥ 24 mmHg or an increase of ≥ 5 mmHg in the IOP from baseline on 2 separate visits that warranted the initiation of ocular hypotensive therapy. The main outcome measured was the development of sustained IOP elevation as defined above. RESULTS: Patients were followed for an average of 47.3 ± 24 months (range, 12-106 months). In the vitrectomized eyes, 38 of the 198 (19.2%) patients developed elevated IOP compared with 9 of the 198 (4.5%) unoperated fellow eyes (P < 0.0001, Fisher exact test; odds ratio, 4.988). Possible risk factors include a family history of open-angle glaucoma (P = 0.0004 Fisher exact test; odds ratio, 7.206) and cataract surgery (P = 0.0270 Fisher exact test; odds ratio, 2.506). CONCLUSION: Uncomplicated PPV seems to increase the IOP, particularly in those who are pseudophakic and have a family history of open-angle glaucoma. This increase in IOP may lead to glaucomatous damage if not managed appropriately. Patients with a previous PPV need to be followed by an ophthalmologist to monitor the IOP in the vitrectomized eye.

Physical activity in end-stage renal disease patients: a pilot project in Puerto Rico.

OBJECTIVE: Physical activity has been found to have a positive effect on the clinical outcomes of patients with chronic diseases, including end-stage renal disease (ESRD). The purpose of this study was to describe end-stage renal disease patients on hemodialysis and describe, as well, their physical activity levels. METHODS: Participants were recruited from the renal unit of Hospital Universitario in San Juan. The variables of interest were 1) socio-demographic and health status information and 2) physical activity levels and patterns. RESULTS: Thirty-one participants with end-stage renal disease completed the questionnaires (17 men and 14 women). The average age of the participants was 54+17 years. Eighty-seven percent (87%) answered that they were not active before beginning hemodialysis treatment. Only 4 patients were employed. These four patients performed activities of moderate intensity ranging from 0 to 2267 MET-mins/week. Nineteen participants reported that they performed a variety of household chores. Home physical activity scores consisted of an average of 1025+1856 MET-mins/week (median 200 MET-mins/week). The total physical activity energy expenditure in leisure-time activities was an average of 111+167 MET-mins/ week. The average total physical activity for all the categories from the IPAQ was an average of 1688+2250 MET-mins/week (median 544 MET-mins/week). They sat for about 454+293 minutes per day (approximately 7.5 hours daily). A Spearman's correlation test found there to be a significant inverse relationship between total physical activity energy expenditure and years in hemodialysis treatment, regardless of age (p = -0.301; p < 0.05). CONCLUSION: In this study, the author describes the physical inactivity in a group of ESRD patients receiving hemodialysis and the significant physical activity variability among them. Moreover, those participants who had been on hemodialysis the longest tended to be the most sedentary, regardless of age. Therefore, it is important to raise awareness, educate and assess, and, if warranted, recommend physical activity to chronic kidney disease patients, including those with end-stage renal disease who are receiving hemodialysis.

Phacoemulsification with implantation of a trifocal intraocular lens in eyes with asteroid hyalosis and synchysis scintillans.

PURPOSE: To compare the visual outcomes in both eyes of patients who undergo phacoemulsification and trifocal intraocular lens (IOL) implantation and have asteroid hyalosis (AH) or synchysis scintillans (SS) in only one eye. METHODS: A retrospective comparative case series was performed. We evaluated uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), predictability, safety, efficacy, and satisfaction after implantation of the same model of trifocal IOL in both eyes (PhysIOL FineVision Pod-F and Micro-F and Rayner RayOne Trifocal). RESULTS: A total of 164 eyes of 82 patients (41 females, 50%) met the inclusion criteria. There were no statistically significant differences in sphere, cylinder, spherical equivalent, UDVA, UIVA, or UNVA between the groups. Postoperative CDVA was slightly better in the control group (logMAR 0.03) than in the AH/SS group (logMAR 0.04) (P: 0.014). There were no statistically significant differences in predictability, safety index, or efficacy index between the groups. Overall subjective satisfaction was good (98.2%). CONCLUSIONS: Visual outcomes and satisfaction are good after implantation of trifocal IOLs in eyes with AH or SS. Therefore, trifocal IOLs should not be ruled out in these patients when no other vitreoretinal disorder is present.

Natural History and Surgical Outcomes of Lamellar Macular Holes.

PURPOSE: To assess the natural history and surgical outcomes of lamellar macular holes (LMHs). DESIGN: Retrospective and consecutive case series. SUBJECTS: Patients with LMHs from multiple tertiary care centers. METHODS: Clinical charts and OCT scans were reviewed. MAIN OUTCOME MEASURES: The visual acuity (VA) changes and the occurrence rate of full-thickness macular hole (FTMH) were studied in both groups. Within the operated group, factors associated with 6-month VA and development of FTMH were explored. RESULTS: One hundred seventy-eight eyes were included, of which 89 were monitored and 89 underwent surgery. In the observation group, the mean VA decreased from 0.25 ± 0.18 to 0.28 ± 0.18 logarithm of the minimum angle of resolution (logMAR; P = 0.13), with 14 eyes (15.7%) that lost ≥ 0.2 logMAR VA, after 45.7 ± 33.3 months. Nine eyes (10.1%) spontaneously developed an FTMH. In the operated group, the mean VA increased from 0.47 ± 0.23 to 0.35 ± 0.25 logMAR at 6 months (P < 0.001) and 0.36 ± 0.28 logMAR (P = 0.001) after 24.1 ± 30.1 months. By multivariate analysis, better baseline VA (P < 0.001), the presence of an epiretinal membrane (P = 0.03), and the peeling of the internal limiting membrane (ILM; P = 0.02), with a greater effect of ILM perihole sparing, were associated with a greater 6-month VA. Perihole epiretinal proliferation sparing was associated with a better postoperative VA by univariate analysis (P = 0.03), but this was not significant by multivariate analysis. Eight eyes (9.0%) developed a postoperative FTMH. Using Cox proportional hazard ratios [HRs], pseudophakia at baseline (HR, 0.06; 95% confidence interval [CI], 0.00-0.75; P = 0.03) and peeling of the ILM (HR, 0.05; 95% CI, 0.01-0.39; P = 0.004) were protective factors, while ellipsoid zone disruption (HR, 10.5; 95% CI, 1.04-105; P = 0.05) was associated with an increased risk of FTMH. CONCLUSION: Observed eyes with LMH experienced, on average, progressive VA loss. Patients with LMH and altered vision may benefit from surgery. Internal limiting membrane peeling, with perihole ILM sparing, represents a crucial step of the surgery associated with a greater VA and a lower risk of postoperative FTMH. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.

PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide. DESIGN: Multicenter national nAMD database observational study. SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification. MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions. CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.