Mean Central Subfield Thickness Research Articles

Punctate hyperreflective vitreous opacities: a ubiquitous finding in healthy children beyond infancy.

The vitreous evolves from birth over lifetime. Little is known about the appearance of the healthy vitreous during childhood. We aimed to characterise posterior vitreous features in healthy children using spectral domain optical coherence tomography (SD-OCT). Retrospective cohort study including healthy eyes of 78 children aged 2-12 years and 39 healthy adults. Patients diagnosed with intraocular inflammation or vitreoretinal pathology were excluded. Proportion of eyes with presence of punctate hyperreflective vitreous opacities (PHVO). Percentage of B-scans demonstrating PHVO within an OCT volume scan, correlation between presence of PHVO and patients' age group, retinal measurements, and presence of premacular bursa were analysed. 154 paediatric eyes (median age 9.08 (IQR 5.17-9.75) years) and 76 adult eyes (30.75 (IQR 26.42-38.08) years) were included; 12244 OCT images were reviewed. All eyes (100%) in the paediatric group and 73% in the adult group presented PHVO. The median percentage of OCT images showing PHVO was 77.05% (IQR 51.23-88.52) in children and 8.0% (IQR 0-16.03) in adults (p < 0.001). Separate analysis of right and left eyes confirmed the results (p < 0001). Premacular bursa appeared in 20.5% of paediatric and 31.6% of adult eyes (p = 0.103). Mean central subfield thickness was significantly lower in children (257 ± 21 µm vs. 276 ± 18 µm, p < 0.001), while median total macular volume was similar (8.59 (IQR 8.25-8.86) mm3 vs. 8.62 (IQR 8.39-8.96) mm3, p = 0.145). This study demonstrates that PHVO are ubiquitous physiologic vitreous findings in healthy children beyond infancy. These findings enhance the understanding of the development of the posterior segment of the eye and might improve paediatric OCT interpretation, potentially avoiding misdiagnoses and unnecessary interventions in children.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema

ObjectiveTo investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME).MethodsForty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 μm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity.ResultsOne-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed.ConclusionThe SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME.Clinical Trial Number (CAAE)22969019.4.0000.5440.

Association of Various Optical Coherence Tomographic Patterns of Diabetic Macular Edema With Central Subfield Thickness and Visual Acuity: A Cross-Sectional Observational Study.

Introduction Diabetic macular edema (DME) is the most common and vision-threatening complication in diabetic patients with diabetic retinopathy (DR), especially in those with Type 2 diabetes mellitus. Optical coherence tomography (OCT) is a reliable tool most commonly used for assessing macular morphology and provides quantitative information on the macula. OCT also examines the outer retinal layers, which can predict visual outcomes. Thus, our study aims to identify the association of various OCT-detected DME morphological patterns with central subfield thickness (CST) and visual acuity. Materials and methods This is a cross-sectional observational study of 50 patients with DME detected on OCT who visited the Ophthalmology Department of Saveetha Medical College and Hospitals for a period of six months, from November 2023 to April 2024. A complete ocular examination, including best corrected visual acuity, scored with the logMAR scale, anterior segment examination, and fundus biomicroscopy using 90D and 78D lenses, was performed. Early Treatment of Diabetic Retinopathy Study (ETDRS) grading of DR into mild to very severe non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) was noted. Spectral-domain OCT was used to diagnose DME. The CST was measured, and DME was classified into four patterns: sponge-like retinal swelling (SLRS), cystoid macular edema (CME), subretinal fluid (SRF), and posterior hyaloid traction (PHT). Results In the present study, males represented 60%, and females represented 40%. The mean age of the patients was 58.07 ± 6.80 years, with a mean duration of diabetes of 11.91 ± 5.14 years. Of the 50 patients with 100 eyes, only 60 eyes showed DME on OCT. CME was the most common morphological pattern (37%), while the least common pattern was PHT (10%). No significant association was found between a specific morphological pattern and control of diabetes. The most common pattern observed was SLRS in moderate NPDR, CME in severe NPDR, SRF in very severe NPDR, and PHT in PDR. Very severe NPDR patients showed all patterns of DME, and the PHT pattern was observed only in very severe NPDR and PDR. The highest mean CST was observed in the very severe NPDR stage, and the least was in the moderate NPDR stage. The mean CST was highest in SRF patterns and lowest in SLRS patterns. The best mean visual acuity was observed in the SLRS pattern, while the worst mean visual acuity was observed in the SRF pattern, followed by the PHT pattern. Conclusion Our study highlights the importance of OCT in patients with diabetes, as OCT patterns of DME are critical for predicting visual outcomes in DR. Severe grades of DR are usually associated with SRF and PHT patterns. Since patients with SRF and PHT patterns have the worst visual outcomes, these patients, upon identification, need to be counseled about their poor visual prognosis. Those with less severe DR should be closely monitored and advised on effective diabetes control to prevent progression and protect their vision.

Pro Re Nata brolucizumab for early onset and treatment-naïve diabetic macular edema: A prospective study.

To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up. Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year. A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events. Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

Real-World 1-Year Outcomes of Treatment-Intensive Neovascular Age-Related Macular Degeneration Switched to Faricimab

PurposeTo report one-year anatomical and functional real-world outcomes of treatment intensive neovascular age related macular degeneration (nAMD) patients switched to faricimab DesignRetrospective multi-centre cohort study SubjectsConsecutive nAMD patients on 4-weekly treatment interval with either ranibizumab or aflibercept 2mg in the last three visits within a treat and extend protocol (high treatment burden) prior to switch to faricimab at Moorfields Eye Hospital between 5/9/2022- 5/12/2022. MethodsTotal number of nAMD patients switched to faricimab were identified from electronic medical records and those who met criteria of high treatment burden were included. Data collected included pre and post-switch visual acuity (VA), treatment intervals, length of follow-up, baseline macular morphology, changes in central subfield thickness (CST), macular fluid status and adverse events. Main outcome measuresVA, CST, presence of intraretinal fluid (IRF), subretinal fluid (SRF) and injection intervals over one-year following switch to faricimab. ResultsA total of 130/ 286 (45.5%) eyes met inclusion criteria of being switched due to high treatment burden and 117 were included in analysis. Prior to switch to faricimab, these eyes received mean total number of injections of 33.4±19.6 over mean of 51.3±34.9 months. Mean number of injections in 12 months preceding switch was 10.1±1.6 and mean interval of the preceding three injections was 4.2±0.3 weeks. Mean VA, CST and percentage of patients with dry macula prior to switch were 66.0±11.9 ETDRS letters, 259.6±76.0μm and 18.3% respectively. Following switch, there was no statistical difference in mean VA after each visit and at 12 months. Mean CST statistically significantly reduced following the 3rd faricimab injection and at 12 months by 20.0μm (p=0.035) and 22.1μm (p=0.041) respectively. Mean treatment intervals increased to 6.9±2.3 weeks (p<0.005) at 12 months with 42.9% and 11.4% of patients being on ≥8 weekly and ≥12 weekly treatment intervals respectively. ConclusionAt 12 months, patients with nAMD with previous record of high treatment burden when switched to faricimab maintained visual acuities and improved anatomical outcomes on extended treatment intervals. Physician bias is inherent in these types of observational studies so a prospective randomised controlled trial is recommended to validate these findings.

Real-World Outcomes of a Loading Phase with Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration (n-AMD) and Diabetic Macular Edema (DME).

The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration (n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers. Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit. Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (± standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (± 0.43) to 0.53 (± 0.36; P = 0.13) and from 0.51 (± 0.34) to 0.32 (± 0.24; P: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: - 166.5μm; P = 0.0009/DME: - 110.8μm; P = 0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (> 100μm) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME. Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME.

Supplemental Intravitreal Ranibizumab Injections in Eyes Treated with the Port Delivery System with Ranibizumab in the Archway Trial

PurposeTo determine the proportion and characteristics of eyes with neovascular age-related macular degeneration (nAMD) treated with the Port Delivery System with ranibizumab (PDS) that receive supplemental intravitreal ranibizumab injections due to changes in best-corrected visual acuity (BCVA) and/or central subfield thickness (CST), and to investigate the safety and efficacy of supplemental injections in eyes with the PDS. DesignPost-hoc analyses of data from the phase 3, randomized, multicenter, open-label, active-comparator Archway trial (NCT03677934). ParticipantsAdults with nAMD diagnosed within 9 months of screening previously responsive to anti–vascular endothelial growth factor (anti-VEGF) therapy. Intervention418 patients were randomized to the PDS with ranibizumab 100 mg/mL with fixed refill-exchanges every 24 weeks (Q24W) or monthly intravitreal ranibizumab 0.5 mg for 96 weeks. ResultsOf the 246 eyes treated with the PDS Q24W and assessed for supplemental treatment criteria, the vast majority (94.6%–98.4%) did not receive supplemental treatment during each retreatment interval, with 87.4% not receiving supplemental treatment at any point during the trial. Of the 31 eyes receiving supplemental treatment, 58.1% received 1 injection and 32.3% received 2. At baseline, eyes receiving supplemental treatment were significantly more likely to have thicker retinas (mean CST 370.5μm vs 304.4μm; P = 0.0001), subretinal fluid (54.8% vs 21.2%; P < 0.0001), and larger pigment epithelial detachment height (215.7μm versus 175.9μm; P = 0.003). These features have previously been associated with difficult-to-treat nAMD. Whereas BCVA and CST generally remained constant throughout the trial in eyes without supplemental treatment, the small number of eyes receiving supplemental treatment on average lost 1 line of vision from baseline to week 96 (mean –5.7 Early Treatment Diabetic Retinopathy Study score letters) and CST continued to increase over time. Absolute BCVA at week 96 was similar irrespective of supplemental treatment status (71.1 and 73.7 letters). BCVA and CST generally improved within 28 days of supplemental treatment. ConclusionsAlthough the PDS Q24W effectively maintains vision and retinal stability in most eyes with nAMD, a small proportion of patients with features of difficult-to-treat nAMD may benefit from supplemental intravitreal anti-VEGF injections and initial close monitoring is recommended.

Phase I Study of Tivozanib Eye Drops in Healthy Volunteers and Patients with Neovascular Age-Related Macular Degeneration

PurposeTo evaluate the safety, pharmacokinetics, and exploratory efficacy of tivozanib eye drops in healthy volunteers and patients with neovascular age-related macular degeneration (nAMD). DesignThis multicenter, group-sequential dose escalation phase 1 study consisted of a placebo-controlled, double-masked study of healthy volunteers (Cohorts 1 and 2) and an open-label study of nAMD patients (Cohort 3). ParticipantsHealthy volunteers: Japanese or White men aged 20 to <50 years. Patients with nAMD with central subfield thickness ≥300 μm and best-corrected visual acuity score ≥23 letters in the study eye. MethodsIn the single-dose cohort of healthy men (Cohort 1: Steps 1–5), 1 or 2 tivozanib eye drops (30 μL/drop, 5-minute interval; 0.5, 1.0, and 2.0 w/v%) or placebo were administered in 1 eye once. In the multiple-dose cohort of healthy men (Cohort 2: Steps 1–6), 1 or 2 tivozanib eye drops (0.5, 1.0, and 2.0 w/v%) or placebo were administered 3 times daily (TID) in 1 eye for 21 days. In the multiple-dose cohort of nAMD patients (Cohort 3, Steps 1–3), 1 or 2 tivozanib eye drops (0.5 and 1.0 w/v%) were administered TID in 1 affected eye for 21 days. Main Outcome MeasuresThe safety outcome measures included adverse events (AEs). The pharmacokinetic outcome was serum tivozanib concentration. Among the exploratory efficacy outcomes, central subfield thickness (CST) was evaluated. ResultsIn total, 40, 48, and 28 participants were enrolled in Cohorts 1, 2, and 3, respectively. Serious AEs did not occur in Cohorts 1–3. The most frequent AE in multiple-dose cohorts was reversible punctate keratitis: placebo arm, 8.3% (healthy men, 1/12); tivozanib arm, 47.2% (healthy men, 17/36) and 14.3% (nAMD, 4/28). Serum tivozanib exposure increased dose-dependently and was similar in healthy men and patients with nAMD. In patients with nAMD, mean CST changes from baseline to Day 22 were −27.6 ± 54.88 (0.5 w/v%; 1 drop, TID), −35.6 ± 49.64 (1.0 w/v%; 1 drop, TID), and −43.7 ± 55.19 μm (1.0 w/v%; 2 drops, TID). ConclusionsTivozanib eye drops showed a favorable safety profile in healthy Japanese and White men and Japanese patients with nAMD.

Treatment Outcomes of Intravitreal Aflibercept for Uveitic Macular Edema.

To evaluate the efficacy of intravitreal aflibercept for UME (uveitic macular). A retrospective review of records of patients that received aflibercept for UME from January 2017 to August 2022 was conducted. The primary outcomes were mean change in visual acuity (VA) and central subfield thickness (CST) 6 and 12 months from the start of aflibercept treatment. A total of 16 eyes of 12 patients were included. Indications for treatment included eyes that had previously demonstrated a history of elevated intraocular pressure secondary to a steroid response (n = 10) or a history of non-response or partial response to local corticosteroids (n = 6). Fifteen eyes (94%) demonstrated a reduction in CST after their initial injection. At 6-months, mean VA gain was 2.6 ± 7.7 letters (p = 0.24) from a mean VA of 67.8 ± 10.7 letters at baseline and mean CST improved by 97.6 ± 113.5 μm (p = 0.004) from 458.6 ± 123.1 μm at baseline. Fourteen eyes had 12-months of follow up and received a median of 4 injections over 12 visits. The mean VA at 12-months remained stable compared to baseline (mean change of -1.4 ± 12.5 letters (p = 0.87)) while the CST improved by a mean of 90.9 ± 114.6 μm (p = 0.053) compared to baseline. Intravitreal aflibercept injections resulted in reduced central subfield thickness at all time-points. It appears to be an effective treatment alternative for UME, particularly for patients who are not responsive to local corticosteroids or who have contraindications to corticosteroid treatment.

Real-World Outcomes of the 0.19 mg Fluocinolone Acetonide Intravitreal Implant for Diabetic Macular Edema.

Purpose: To evaluate the real-world clinical and safety outcomes of a 0.19 mg fluocinolone acetonide intravitreal implant to treat diabetic macular edema (DME). Methods: This retrospective analysis comprised patients treated with a single fluocinolone acetonide intravitreal implant for the clinical indication of ME secondary to diabetic retinopathy. Primary outcomes included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and the frequency of DME-related treatments 12 months before and up to 36 months after fluocinolone acetonide administration. Safety outcomes were also assessed. Results: One hundred forty-eight eyes (115 patients) were followed for a mean (±SD) of 12.3 ± 4.2 months before and 29.4 ± 14.5 months after fluocinolone acetonide administration. A 0.8-letter decrease (Early Treatment Diabetic Retinopathy Study) in the mean BCVA was observed at month 24. The BCVA was 70 letters (20/40 Snellen equivalent) or more in 20.6% of eyes at baseline and in 23.7% of eyes 24 months after implant administration. The mean CST was 379.9 μm and 323.7 μm, respectively. The CST was 300 μm or less in 58.7% of eyes at month 24 (P < .001). The mean frequency of intravitreal antivascular endothelial growth factor injections or laser photocoagulation decreased from 4.9 to 1.5 per year after fluocinolone acetonide administration (P < .001). Implant migration to the anterior chamber occurred in 3 eyes, 2 of which were vitrectomized and later required removal. Conclusions: The 0.19 mg fluocinolone acetonide intravitreal implant provided long-term stabilization of VA and macular anatomy in patients with DME, despite a significant reduction in treatment frequency.

Retinal and choroidal efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration

Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.

One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry

PurposeTo compare one-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal vascular endothelial growth factor (VEGF) inhibitor injections were delivered. DesignCohort study ParticipantsThere were 2288 treatment-naïve eyes with DME starting intravitreal VEGF inhibitor therapy from 31 October 2015 to 31 October 2021 from the Fight Retinal Blindness! international outcomes registry. MethodsEyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n=1172) versus Group B with greater than the median (n=1116). Main Outcome MeasureMean visual acuity (VA) change after 12 months of treatment. ResultsThe mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8, 4.4) letters for eyes in Group A versus 5.2 (4.4, 5.9) letters for eyes in Group B (p=0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76, -61) μm and -85 (-92, -78) μm for eyes in Group A versus Group B, respectively (p=0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (p<0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. ConclusionsThis registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy.

Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.7, anti-VEGF + 10.6 letters; CRVO: DEX + 2.8, anti-VEGF + 6.8 letters). DEX initiated eyes had fewer injections and visits than anti-VEGF initiated eyes. The BRVO-DEX eyes had greater initial mean changes in VA and central subfield thickness (CST) and achieved inactivity sooner than BRVO-anti-VEGF eyes. The mean CST after the first three months was above 350 μm in all but the BRVO-anti-VEGF group, suggesting undertreatment. In routine care DEX is uncommonly used when available as initial treatment of BRVO and CRVO requiring supplemental anti-VEGF within the first year. The 12-month outcomes were similar, but DEX initiated eyes had fewer injections and visits but more episodes of raised IOP Vs those starting anti-VEGF.

The effect of glycosylated hemoglobin levels on the response to intravitreal dexamethasone implant for treating diabetic macular edema

This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was − 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Two-Year Follow-Up Study of Patients with Neovascular Age-Related Macular Degeneration Undergoing Anti-VEGF Treatment during the COVID-19 Pandemic

Background: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression. Methods: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic. Results: The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 ± 1.51 months (p = 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (p &lt; 0.001). The delayed group showed greater mean BCVA deterioration (p = 0.027) and central subfield thickness (p = 0.037) at 6 months and worse maximum subretinal fluid height (p = 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year. Conclusion: the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals.

Safety and Efficacy of CLS-TA by Anatomic Location of Inflammation: Results from the Phase 3 PEACHTREE Clinical Trial

ABSTRACT Purpose To explore the efficacy of CLS-TA, a proprietary suprachoroidal injectable suspension of triamcinolone acetonide, in noninfectious uveitis (NIU) with macular edema (ME), categorized by anatomic subtype. Methods Patients diagnosed with ME associated with NIU of any etiology and anatomic subtype were eligible for the phase 3 PEACHTREE trial of CLS-TA. Post-hoc analyses were performed, stratified by discrete anatomic subtype of uveitis (anterior, intermediate, posterior, and panuveitis.) Results Across all anatomic subtypes at 24 weeks, patients receiving CLS-TA at baseline and week 12 demonstrated mean increases in BCVA ranging from +12.1 to +15.9 letters, mean central subfield thickness (CST) improvement ranging from −120.1 µm to −189.0 µm, and IOP changes ranging from +0.5 to +3.1 mmHg. Overall, reports of adverse events were similar among subtypes. Conclusions Irrespective of the uveitic anatomic subtype among patients treated for ME associated with NIU, a clinical benefit in participants treated with CLS-TA was demonstrated, with a comparable safety profile.

Efficacy and Safety of Faricimab for Macular Edema due to Retinal Vein Occlusion: 24-Week Results from the BALATON and COMINO Trials

To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion. Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192). Patients with treatment-naïve foveal center-involved macular edema resulting from branch (BALATON) or central or hemiretinal (COMINO) RVO. Patients were randomized 1:1 to faricimab 6.0 mg or aflibercept 2.0 mg every 4 weeks for 24weeks. Primary end point: change in best-corrected visual acuity (BCVA) from baseline to week 24. Efficacy analyses included patients in the intention-to-treat population. Safety analyses included patients who received ≥ 1 doses of study drug. Enrollment: BALATON, n = 553; COMINO, n = 729. The BCVA gains from the baseline to week 24 with faricimab were noninferior versus aflibercept in BALATON (adjusted mean change,+16.9 letters [95.03% confidence interval (CI), 15.7-18.1 letters] vs.+17.5 letters [95.03% CI, 16.3-18.6 letters]) and COMINO (+16.9 letters [95.03% CI, 15.4-18.3 letters] vs.+17.3 letters [95.03% CI, 15.9-18.8 letters]). Adjusted mean central subfield thickness reductions from the baseline were comparable for faricimab and aflibercept at week 24 in BALATON (-311.4 μm [95.03% CI,-316.4 to-306.4 μm] and-304.4 μm [95.03% CI,-309.3 to-299.4 μm]) and COMINO (-461.6 μm [95.03% CI,-471.4 to-451.9 μm] and-448.8 μm [95.03% CI,-458.6 to-439.0 μm]). A greater proportion of patients in the faricimab versus aflibercept arm achieved absence of fluorescein angiography-based macular leakage at week 24 in BALATON (33.6% vs. 21.0%; nominal P= 0.0023) and COMINO (44.4% vs. 30.0%; nominal P= 0.0002). Faricimab was well tolerated, with an acceptable safety profile comparable with aflibercept. The incidence of ocular adverse events was similar between patients receiving faricimab (16.3% [n= 45] and 23.0% [n= 84] in BALATON and COMINO, respectively) and aflibercept (20.4% [n= 56] and 27.7% [n= 100], respectively). These findings demonstrate the efficacy and safety of faricimab, a dual Ang-2/VEGF-A inhibitor, in patients with macular edema secondary to retinal vein occlusion. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

XTEND: Two-Year Results from a Global Observational Study Investigating Proactive Dosing of Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration.

XTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels. Study eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive. Overall, 1466 patients from 17 countries were treated. For the overall population, the mean ± standard deviation (SD) age was 78.7 ± 8.5 (range 50-100)years, and 891 patients (60.8%) were female. The mean ± SD baseline BCVA was 54.3 ± 20.3 letters and CST was 374 ± 126µm. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was + 4.3 (3.4, 5.3) and + 2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was - 106 (- 114, - 99) μm and - 109 (- 117, - 102) μm at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA ≥ 70 letters. Patients received a mean ± SD of 7.7 ± 2.7 injections by M12 and 10.8 ± 5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL. The 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-naïve nAMD. The proportion of patients achieving ≥ 70 letters at M24 increased, and patients with baseline BCVA ≥ 70 letters maintained vision regardless of the followed IVT-AFL label. ClinicalTrials.gov identifier: NCT03939767. A video abstract is available for this article. Supplementary file2 (MP4 364624 KB).

Real-World Outcomes of Faricimab Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

The purpose of this study was to assess preliminary real-world outcomes in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) treated with intravitreal faricimab. This was a retrospective, observational consecutive-case real-world study of patients with nAMD or DME initiated on intravitreal faricimab between November 2022 and April 2023. Treatment-naïve patients and patients previously treated with alternate anti-vascular endothelial growth factor (anti-VEGF) agents were initiated on an intended treatment plan of four monthly faricimab injections as a loading regime. Efficacy was assessed across four treatment groups. Primary outcomes assessed for both cohorts were changes in best corrected visual acuity (BCVA) and central subfield thickness (CST) on optical coherence tomography (OCT). Secondary outcomes were alterations in OCT-defined structural features. From 127 patients, 146 eyes received at least one dose of faricimab. Mean BCVA, measured in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, from baseline to fifth visit increased from: 59.0±12.8 to 62.2±14.3 in treatment-naïve nAMD; 61.1±17.6 to 63.5±14.8 in previously-treated nAMD; 61.1±13.0 to 72.8±11.5 in treatment-naïve DME; and 60.8±14.6 to 63.3±15.6 in previously-treated DME. Mean CST reduced in all four treatment groups between initiation to final loading dose, from: 442.8±172.0µm to 305.2±117.0µm (p<0.0001) in treatment-naïve nAMD; 355.2±115.1µm to 297.9±92.54µm (p<0.0001) in previously-treated nAMD; 465.8±109.1µm to 343.1±100.3µm (p<0.0001) in treatment-naïve DME; and 492.5±133.1µm to 388.5±131.4µm (p<0.0001) in previously-treated DME. Real-world outcomes showed some improvement in BCVA and CST for nAMD and DME following faricimab administration, including in patients previously treated with other anti-VEGF agents. Further work involving larger cohorts over longer periods is required to determine whether improvement is maintained, and if intervals can be extended to match those observed in clinical trials.

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

PurposeTo evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend–based regimen (T&E) with up to every-16-week (Q16W) dosing in the YOSEMITE/RHINE (NCT03622580/NCT03622593) phase 3 trials of diabetic macular edema (DME). DesignRandomized, double-masked, noninferiority phase 3 trials. ParticipantsAdults with visual acuity loss due to center-involving DME. MethodsPatients were randomized 1:1:1 to faricimab 6.0 mg Q8W, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg Q8W. The T&E up to Q16W dosing regimen was based on central subfield thickness (CST) and best-corrected visual acuity (BCVA) change. Main Outcome MeasuresIncluded changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. ResultsIn YOSEMITE/RHINE (N=940/951), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92/96/100 average) with faricimab Q8W (YOSEMITE/RHINE, +10.7/+10.9 letters) or T&E (+10.7/+10.1 letters) were comparable with aflibercept Q8W (+11.4/+9.4 letters). The median number of study drug injections was lower with faricimab T&E (YOSEMITE/RHINE, 10/11 injections) versus faricimab Q8W (15 injections) and aflibercept Q8W (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was further improved during year 2, with >60% of patients on Q16W dosing and ∼80% on ≥Q12W dosing at week 96. Almost 80% of patients who achieved Q16W dosing at week 52 maintained Q16W dosing without an interval reduction through week 96. Mean CST reductions were greater, and more patients achieved absence of DME (CST <325μm) and absence of intraretinal fluid with faricimab Q8W or T&E versus aflibercept Q8W through year 2. Overall, faricimab was well tolerated, with a safety profile comparable to aflibercept. ConclusionsClinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to Q16W were maintained through year 2. Faricimab given as a personalized T&E–based dosing regimen supports the role of dual angiopoietin-2/VEGF-A inhibition to promote vascular stability and provide durable efficacy for patients with DME.