Faricimab for the Treatment of Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.

Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients and long-term visual acuity decline due to complications such as macular atrophy and fibrosis. Targeting the angiopoietin/Tie (Ang/Tie) pathway beyond the VEGF pathway may be a possible therapeutic strategy; which may has the potential to solve some of the previous mentioned challenges. Faricimab is a new; bispecific antibody targeting both VEGF-A and the Ang-Tie/pathway. It was approved by FDA and; more recently; by EMA for treating w-AMD and DME. Results from phase III trials TENAYA and LUCERNE (w-AMD) and RHINE and YOSEMITE (DME) have shown the potential of faricimab to maintain clinical efficacy with more prolonged treatment regimens compared to aflibercept (12 or 16 weeks) with a a good safety profile

Comparison of Indocyanine Green Angiography and Swept-Source Wide-Field Optical Coherence Tomography Angiography in Posterior Uveitis

Purpose: To compare indocyanine green angiography (ICGA) and swept-source wide-field optical coherence tomography angiography (SS-OCTA) for the assessment of patients with posterior uveitis. Method: SS-OCTA montage images of 5 x 12 x 12 mm or 2 x 15 x 9 mm, covering ~70–90 degree of the retina of consecutive patients with posterior uveitis were acquired. The choriocapillaries and choroidal slabs were compared to findings on ICGA. Results: Sixty-eight eyes of 41 patients were included (mean age 47.2 ± 20.4 years; 58.5% female). In 23 (34%) lesions were visible on OCTA, but not discernable on ICGA. In turn, out of the 45 eyes with clearly discernable lesions on ICGA, 22 (49%) and 21 (47%) eyes showed no corresponding areas of flow deficit on OCTA in the CC and choroidal slab, respectively. Lesion size strongly correlated among ICGA and OCTA choriocapillaries- (CC) (r = 0.99, p ≤ 0.0001) and choroidal slabs (r = 0.99, p ≤ 0.0001), respectively. The mean lesion size on the late frames of ICGA (8.45 ± 5.47 mm2) was larger compared to the lesion size on OCTA CC scan (7.98 ± 5.47 mm2, p ≤ 0.0001) and choroidal scan (7.69 ± 5.10 mm2, p = 0.002), respectively. The lesion size on OCTA CC scan was significantly larger than on the OCTA choroidal scan (p ≤ 0.0001). Conclusion: SS-wide field OCTA may be a promising tool to assess posterior uveitis patients and may replace ICGA to a certain extent in the future

Retinal Tectonics after Macular Pucker Surgery: Thickness Changes and En-Face Displacement Recovery.

PURPOSE To study visual function, retinal layer thickness changes and tangential displacement after Pars Plana Vitrectomy (PPV) for EpiRetinal Membrane (ERM). METHODS Retrospective series of patients undergoing PPV for ERM, with 6-month follow-up including best-corrected visual acuity (BCVA), Optical Coherence Tomography (OCT), M-charts, ERM grading, and InfraRed fundus photo at time 0 (T0, pre-op) at month 1 (T1), 3 (T3), 6 (T6) post-op (±1 week). Retinal layer thickness and tangential (en-face) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En-face displacement was calculated as optical flow of consecutive images. RESULTS Average BCVA improved from 0.28±0.08 logMAR at T0 to 0.16±0.25 at T6 (p=0.05), BCVA improvement correlated with BVCA at T0 (p<0.001). Vertical metamorphopsia decreased from 1.33°±0.70° at T0 to 0.82°±0.69° at T6 (p<0.05). Foveal thickness reduced from 453±53µm at T0 to 359±31µm at T6 (p<0.05) and reduction correlated with BCVA improvement (p<0.05). Foveal layers decreased (p<0.05) in all cases. Mean en-face deformation was 155.82±50.17µm and mostly occurred in the first month: T0-T1 displacement was 83.59±30.28µm, T1-T3 was 36.28±14.45µm, while T3-T6 was 39.11±22.79µm (p<0.001) on average. Peri-foveal and parafoveal deformation correlated with OCT foveal thickness reduction at all time intervals (1, 3, 6 months: p<0.01). CONCLUSION ERM peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en-face and in-depth changes correlate with visual function

Topical treatment of diabetic macular edema using dexamethasone ophthalmic suspension: A randomized, double-masked, vehicle-controlled study.

PURPOSE To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME). METHODS This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of 0. RESULTS Mean CMT showed a greater decrease from baseline with OCS-01 (N = 99) than vehicle (N = 45) at Week 12 (-53.6 vs -16.8 μm, p = 0.0115), with significant differences favouring OCS-01 from Weeks 2 to 12. OCS-01 was well-tolerated, and increased intraocular pressure was the most common adverse event. Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS-01 and 1 letter with vehicle (p = 0.125). In a post-hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS-01 group improved 3.8 letters compared with 0.9 letters with vehicle. CONCLUSION Topical OCS-01 was significantly more effective than vehicle in improving central macular thickness in patients with DME. Visual improvement was better in eyes with lower baseline vision

Herpetic anterior uveitis following COVID-19 vaccines: a case series

PurposeTo report a case series of herpetic uveitis following COVID-19 vaccinations.MethodsDemographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well.ResultsTwenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28–83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3–42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2.ConclusionThis report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing

The Role of Intravitreal Corticosteroids in the Treatment of DME: Predictive OCT Biomarkers

Abstract: This work aims to summarize predictive biomarkers to guide treatment choice in DME. Intravitreal anti-VEGF is considered the gold standard treatment for centers involving DME, while intravitreal steroid treatment has been established as a second-line treatment in DME. However, more than 1/3 of the patients do not adequately respond to anti-VEGF treatment despite up to 4-weekly injections. Not surprisingly, insufficient response to anti-VEGF therapy has been linked to low-normal VEGF levels in the serum and aqueous humor. These patients may well benefit from an early switch to intravitreal steroid treatment. In these patients, morphological biomarkers visible in OCT may predict treatment response and guide treatment decisions. Namely, the presence of a large amount of retinal and choroidal hyperreflective foci, disruption of the outer retinal layers and other signs of chronicity such as intraretinal cysts extending into the outer retina and a lower choroidal vascular index are all signs suggestive of a favorable treatment response of steroids compared to anti-VEGF. This paper summarizes predictive biomarkers in DME in order to assist individual treatment decisions in DME. These markers will help to identify DME patients who may benefit from primary dexamethasone treatment or an early switc

Herpetic anterior uveitis following COVID-19 vaccines: a case series.

PURPOSE To report a case series of herpetic uveitis following COVID-19 vaccinations. METHODS Demographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well. RESULTS Twenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28-83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3-42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2. CONCLUSION This report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

INTRODUCTION Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. METHODS The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm). RESULTS LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. CONCLUSION These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. TRIAL REGISTRATION Clinicaltrial.Gov Registration Identifier: NCT03878420

Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations.

Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity

Idiopathic multifocal choroiditis/punctate inner choroidopathy with acute photoreceptor loss or dysfunction out of proportion to clinically visible lesions.

PURPOSE To report acute/subacute vision loss and paracentral scotomata in patients with idiopathic multifocal choroiditis/punctate inner choroidopathy due to large zones of acute photoreceptor attenuation surrounding the chorioretinal lesions. METHODS Multimodal imaging case series. RESULTS Six women and 2 men were included (mean age, 31.5 ± 5.8 years). Vision ranged from 20/20-1 to hand motion (mean, 20/364). Spectral domain optical coherence tomography demonstrated extensive attenuation of the external limiting membrane, ellipsoid and interdigitation zones, adjacent to the visible multifocal choroiditis/punctate inner choroidopathy lesions. The corresponding areas were hyperautofluorescent on fundus autofluorescence and were associated with corresponding visual field defects. Full-field electroretinogram (available in three cases) showed markedly decreased cone/rod response, and multifocal electroretinogram revealed reduced amplitudes and increased implicit times in two cases. Three patients received no treatment, the remaining were treated with oral corticosteroids (n = 4), oral acyclovir/valacyclovir (n = 2), intravitreal/posterior subtenon triamcinolone acetate (n = 3), and anti-vascular endothelial growth factor (n = 2). Visual recovery occurred in only three cases of whom two were treated. Varying morphological recovery was found in six cases, associated with decrease in hyperautofluorescence on fundus autofluorescence. CONCLUSION Multifocal choroiditis/punctate inner choroidopathy can present with transient or permanent central photoreceptor attenuation/loss. This presentation is likely a variant of multifocal choroiditis/punctate inner choroidopathy with chorioretinal atrophy. Associated changes are best evaluated using multimodal imaging