Macular Leakage Research Articles

Tocilizumab for cystoid macular edema secondary to retinitis pigmentosa

PurposeTo describe the effect of tocilizumab (TCZ) on cystoid macular edema (CME) and retinal vascular leakage (RVL) in retinitis pigmentosa (RP).MethodsRetrospective case series.ResultsWe present 2 cases of RP with marked inflammatory features in the form of CME and RVL. There was initial diagnostic uncertainty with posterior uveitis. Both patients were treated with corticosteroids, conventional disease-modifying antirheumatic drugs (cDMARDs), and biological DMARDs (bDMARDs) for the inflammatory features with partial and inconsistent treatment response. When treatment was switched to intravenous (IV) TCZ, dramatic reduction in CME and RVL were observed in both patients. Diagnosis of RP was eventually made based on findings of ancillary tests (macular spectral-domain optical coherence tomography, visual fields, full-field electroretinogram). Genetic testing led to a molecular diagnosis of EYS-related autosomal recessive RP in patient 1, while patient 2 had negative gene panel results.ConclusionsIV TCZ can be an effective treatment option in RP-related CME and RVL. Whether this treatment strategy has an effect on prognosis remains to be established, but it is possible considering chronic CME-related retinal damage is a major driver of central vision loss in RP.

Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes

AbstractIntravitreal anti–vascular endothelial growth factor (VEGF) therapy is the standard of care for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); however, vision gains and anatomical improvements are not sustained over longer periods of treatment, suggesting other relevant targets may be needed to optimize treatments. Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation. Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE/RHINE) and nAMD (TENAYA/LUCERNE). These trials evaluated faricimab against the anti-VEGFA/B and anti–placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1 year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE/RHINE and TENAYA/LUCERNE. In YOSEMITE/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0–12 weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE/RHINE and TENAYA/LUCERNE. These findings suggest that dual Ang-2/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy.

Ultrawide-field fluorescein angiography features in patients with anterior uveitis

PurposeTo evaluate the utility of ultrawide-field fluorescein angiography (UWFFA) in patients with anterior uveitis by investigating the detection of retinal vascular leakage (RVL) and the subsequent implications on disease diagnosis and management.Study design/materials and methodsPatients, who were referred to the National Eye Institute (NEI) for evaluation of anterior uveitis and underwent UWFFA imaging at the initial visit, were included in this study. The electronic medical records of eligible patients were reviewed. The UWFFA images were assessed for severity of retinal vascular leakage, presence of macular leakage, and optic disc leakage by a two-grader system, and intergrader agreement was calculated using the κ-value. Patients with altered diagnoses and management attributable to UWFFA results were noted.ResultsA total of 93 eyes of 63 patients were included in the study. Of 93 eyes, 31 (33.3%) eyes had RVL on UWFFA, with 26 (28.0%) eyes and 5 (5.4%) eyes showing mild and moderate-severe RVL, respectively. Twenty-five (26.9%) eyes showed macular leakage, and 7 (7.5%) eyes showed optic disc leakage. The κ-values ranged from 0.85 – 0.87 indicating excellent intergrader agreement. Of the 31 eyes with RVL, the diagnosis was changed to anterior/intermediate uveitis for 9 (29.0%) eyes and to panuveitis for 4 (12.9%) eyes. Systemic treatment was escalated in 5 patients.ConclusionOur results suggest that UWFFA imaging is useful in detecting subclinical posterior involvement in patients with anterior uveitis. Moreover, UWFFA results in altered diagnosis and treatment approaches in a portion of patients.

Risk factors for failing sub-Tenon’s triamcinolone acetonide for uveitic macular edema

BackgroundSub-Tenon’s triamcinolone acetonide (STA) is less effective than intravitreal corticosteroids in the treatment of uveitic macular edema (ME), but does have some relative advantages, including substantially lower cost and decreased risk of post-injection ocular hypertension. It would be useful for clinicians to know which eyes may respond well to STA and not necessarily require intravitreal therapy. The objective of this study is to identify risk factors for failing STA for the treatment of uveitic ME.Main bodyA retrospective cohort study was performed. Medical records were reviewed of patients who underwent STA for the treatment of uveitic ME between January 1, 2013, and July 31, 2022, at the University of Colorado Hospital. Uveitic ME was defined by a central subfield thickness (CST) greater than 320 μm or the presence of intra-retinal cystoid spaces on optical coherence tomography (OCT), or by the presence of petaloid macular leakage on fluorescein angiography (FA). Data collected included age, race/ethnicity, sex, history of diabetes mellitus, anatomic classification of uveitis, use of corticosteroids, use of immunomodulatory therapy, presence of intra-retinal fluid on OCT, CST on OCT, and presence of petaloid macular leakage on FA. STA failure was defined as the need for additional therapy within 12 weeks of STA due to persistent or worsening uveitic ME. One hundred eighty eyes from 131 patients were included. Forty-two eyes (23.3%) were considered treatment failures. In univariate and multivariable analysis, higher baseline CST was associated with a higher likelihood of failing STA (OR 1.17 for each 30 μm increase in CST, P = 0.016).ConclusionsSTA, while not as potent as intravitreal corticosteroids for the treatment of uveitic ME, was still an effective therapy, particularly for patients with lower baseline CST. Given its lower side effect profile and cost compared to intravitreal treatments, clinicians could consider STA as an initial treatment for mild uveitic ME.

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.

Novel Outer Retinal Columnar Abnormalities (ORCA) and Non-Vasogenic Cystoid Macular Edema in Dense Deposit Disease.

To describe the occurrence of bilateral outer retinal columnar abnormalities, non-vasogenic cystoid macular edema, and drusen in the context of dense deposit disease. Case report. An 18-year-old female with dense deposit disease was referred to our specialist center for diagnosis and management with findings consistent with bilateral non-vasogenic cystoid macular edema and drusen. She was followed up in our clinic for forty months and treated with acetazolamide and ketorolac drops. Baseline examination revealed bilateral visual acuity (VA) reduction, and macular elevation with peripapillary drusen on fundus biomicroscopy. Optical coherence tomography revealed bilateral hyporeflective cystoid central macula changes, microcystoid changes with increased central subfield thickness (>450 microns), and outer retinal columnar abnormalities (ORCAs). Fluorescein angiography showed no evidence of macular leakage. Electrodiagnostic testing was within normal limits. Over the course of follow-up, she received treatment with acetazolamide 250mg BD PO and ketorolac 0.5% eye drops, with a partial reduction in her edema and improvement in VA. Dense deposit disease is a rare disease secondary to complement cascade dysregulation, associated with drusen. To the best of our knowledge, this is the first report of bilateral non-vasogenic cystoid macular edema and ORCA in a young female patient with dense deposit disease, confirmed with multimodal imaging.

Multimodal imaging in radiation retinopathy following orbital metastasis

Background: Radiation retinopathy is a major cause of vision loss in patients receiving radiotherapy to the head and orbit. Diabetic retinopathy is included in the differential diagnosis owing to similar clinical features, including microaneurysms, cotton-wool spots, hard exudates, and macular edema. The only significant pathological difference is that radiation retinopathy spares pericytes, unlike diabetic retinopathy. Multimodal imaging helps diagnose and predict the prognosis of radiation retinopathy, which is presented in this case report.
 Case Presentation: A 55-year-old woman diagnosed with stage-4 metastatic breast carcinoma presented with gradual diminution of vision in the left eye (OS) over 5 months. Vision in the right eye was lost because of orbital radiotherapy for orbital metastasis. The patient underwent multiple sessions of chemotherapy and radiotherapy. Examination of the left eye revealed a best-corrected distance visual acuity (BCDVA) of 20/30. Fundus examination of the OS revealed multiple cotton-wool spots and retinal hemorrhages. Fundus fluorescein angiography (FFA) showed diffuse macular leakage with capillary nonperfusion. Multicolor imaging (MCI) with Spectralis™ revealed black dots in the blue and green reflectance images, corresponding to capillary dilatation on FFA. Darker dots were more evident in the infrared images. BCDVA improved to 20/20 in OS after tapering the dose of oral steroids for 2 months, with improvements in hemorrhages and cotton-wool spots. Focal laser photocoagulation was recommended for the treatment of persistent macular edema. The patient declined further treatment, was lost to follow-up, and passed away 6 months later.
 Conclusions: This case highlights the importance of multimodal imaging for the identification and classification of radiation retinopathy. MCI using SpectralisTM has been described for the first time in radiation retinopathy and can be used to complement existing imaging modalities. Future studies involving more patients and a longer follow-up duration may provide better results for the applicability of these imaging modalities in the clinical setting.

Comparative study between fundus fluorescein angiography and optical coherence tomography angiography in evaluation of diabetic maculopathy

Background Diabetic maculopathy is a serious consequence of diabetic retinopathy (DR) that greatly affects the visual acuity. Diabetic macular edema (DME) and diabetic macular ischemia (DMI) are major causes of vision affection in diabetic patients. Purpose The aim of this study was to compare fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) in evaluation of diabetic maculopathy. Patients and methods This comparative cross-sectional study was performed on 87 eyes of 54 patients with type I or type II diabetes, older than 18 years old with any diabetic retinal changes, and 108 eyes of 54 control subjects. An ocular examination was performed as well as color fundus photography, FA, and OCTA. Investigations were done on the same day. FA and OCTA findings were summarized and compared. Results The mean age of the patients was 59.4±8.5 years. OCTA was statistically significantly superior to FA in diagnosing DMI. The foveal avascular zone (FAZ) was ischemic (enlarged) in 74 (85.06%) eyes by OCTA compared with only 46 (52.87%) eyes by FA, with a statistically significant difference (P = 0.001). In addition, OCTA detected microaneurysms significantly more than FA (P = 0.001). The mean FAZ area of the control eyes by OCTA was significantly less than in the ischemic eyes (U = 56.602, P < 0.001), while the superficial capillary plexus (SCP) vascular density (VD) and the deep capillary plexus (DCP) VD in the control eyes was statistically significantly higher than in the ischemic eyes (U = 36.984, P < 0.001, and U = 35.955, P < 0.001, respectively). FA showed diffuse leakage (edema) at the macula as the most common pattern of DME that was detected in 37.9% of the eyes followed by focal macular leakage in 18.4% of the eyes and cystoid leakage in 8% of the eyes while 35.5% of the eyes showed no macular edema. Conclusion OCTA is a cornerstone in DMI diagnosis both qualitatively and quantitatively. In addition, it is essential in evaluating the deep retinal vasculature, while FA is essential in diabetic retinopathy grading and in the diagnosis of DME in a qualitative manner. Both investigations are complementary to each other in diabetic maculopathy evaluation.

Are optical coherence tomography and fluorescein angiography comparable for detection of macular edema in Behçet uveitis?

To investigate the role and agreement of spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) for macular edema (ME) diagnosis in Behçet uveitis (BU). Eyes with ME detected by SD-OCT and/or FA were enrolled. Type of ME by SD-OCT and grade of macular leakage (ML) by FA were investigated. Eyes were divided into three groups according to the agreement of tests. Three groups and factors that could affect the compatibility of tests were statistically analyzed. Sixty-one eyes of 61 patients were included. Both imaging methods detected ME in 42.6% of eyes (group 1). In 47.5% of eyes, ME was revealed by OCT (group 2). The remaining 9.8% of the eyes had ME, detected only by FA (group 3). Grade 2 ML by FA was more common in group 1 (p = 0.01). The grade of ML by FA was similar in groups 2 and 3. In group 2, most of the eyes showed diffuse ME by OCT (p < 0.001). Epiretinal membrane was detected more frequently in group 3 (p = 0.005). Duration and activity of uveitis were similar between groups. SD-OCT was able to detect ME in 90% of the eyes with BU. Duration and activity of uveitis were not related to the compatibility of imaging methods.

Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial

To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial. Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294). Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage. A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year. Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days. Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P= 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r= 0.4; P= 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P= 0.002) and macular (6.2% vs. 12.2%; P= 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P= 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P= 0.016). Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Macular Retinoschisis from Optic Disc without a Visible Optic Pit or Advanced Glaucomatous Cupping (No Optic Pit Retinoschisis [NOPIR

To review eyes with peripapillary and macular retinoschisis without a visible optic pit or advanced glaucomatous optic atrophy, or No Optic Pit Retinoschisis (NOPIR). Retrospective multicenter case series. The study included 11 eyes of 11 patients. Retrospective study of eyes with macular retinoschisis without a visible optic pit, advanced optic nerve head cupping, or macular leakage on fluorescein angiography. Visual acuity (VA), retinoschisis resolution, months to resolution, and recurrence of retinoschisis RESULTS: The mean age was 68.1 ± 17.6 years, mean intraocular pressure was 17.4 ± 3.8 mmHg, and the mean spherical equivalent refractive error was-3.1 ± 2.9 diopters. No subject had pathologic myopia. Seven subjects were treated for glaucoma, and 9 subjects had nerve fiber layer defects on OCT. All eyes had retinoschisis in the outer nuclear layer (ONL) in the nasal macula and extending to the edge of the optic disc, and 8 subjects had fovea-involving retinoschisis. Three nonfoveal and 4 fovea-involved eyes were observed, and 4 fovea-involved eyes with vision loss underwent surgery. Surgery involved preoperative juxtapapillary laser followed by vitrectomy and membrane and internal limiting membrane peeling with intraocular gas and face-down position. The mean baseline VA was significantly worse in the surgery group than that in the observation group (P= 0.020). Retinoschisis resolved and vision improved in all surgical cases. The mean resolution time for the surgery group was 2.75 ± 0.96 months, which was shorter than that for the observation group (28.0 ± 21.2 months; P= 0.014). No eye developed recurrence of the retinoschisis after surgery. Peripapillary and macular retinoschisis can develop in eyes without a visible optic pit or advanced glaucomatous cupping. Eyes without foveal involvement and those with foveal involvement but only mild decrease in vision can be observed for spontaneous resolution. If there is persistent foveal involvement with vision loss, surgery can improve vision by resolving the macular retinoschisis. Surgery for fovea-involved macular retinoschisis without a visible optic pit resulted in faster anatomic resolution and better vision recovery. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A comparative study of the effect of conventional hemodialysis versus hemodiafiltration on the eye

Background and aim Hemodiafiltration (HDF) seems to be the gold standard concerning dialysis-aided renal replacements. Hemodialysis (HD) and severe renal failure both have visual side effects, including high intraocular pressure, band keratopathy, macular leakage, red eyes, retinal hemorrhage, and optical neuropathy. The purpose of this study is to examine the impact of routine conventional HD versus routine HDF on ocular problems in individuals with chronic kidney disease (CKD). Patients and methods This prospective cross-sectional observational study was conducted on 200 patients divided into 100 patients of CKD on regular HD three times weekly (4 h duration) (HD group) and 100 patients of CKD on regular HDF three times weekly (4 h duration) (HDF group). clinical interview, routine laboratory tests, and complete eye examination were done on all participants. Results Prior to treatment, there was no significant difference between the HDF and HD categories for either eye’s central foveal thickness, average macular thickness, visual acuity, intraocular pressure, anterior segment, or fundus examination. In addition, no significant difference was observed between both groups after therapy in both eyes. Conclusion Regular HDF and HD treatments administered for 6 months each had no negative impact on ocular parameters.

Quadrant laser photocoagulation trial to ameliorate choroidal congestion in central serous chorioretinopathy.

To investigate the efficacy and safety of quadrant laser photocoagulation to ameliorate the choroidal congestion in central serous choroidopathy (CSC). Historically controlled study. We prospectively studied 20 eyes with acute CSC in the quadrant laser group, in which laser photocoagulation was applied to the macular leakage point(s) as well as the quadrant of the fundus showing vortex vein dilatation. Central choroidal thickness (CCT), vertical diameter of dilated vortex vein, resolution rate of serous retinal detachment (SRD), and visual field were evaluated post-treatment. We also compared the results with those of 18 retrospectively analyzed eyes with acute CSC in an external control group, in which laser photocoagulation had been applied only to the macular leakage point(s). In the quadrant laser group, 2 eyes were excluded from data analysis due to choroidal neovascularization (CNV). CCT was significantly reduced in both groups, but more significantly in the quadrant laser group. The vertical diameter of the dilated vortex vein was significantly decreased only in the quadrant laser group. The resolution rate of SRD was similar in the two groups. In the quadrant laser group, 8 eyes (44.4%) showed mild deterioration of the visual field, consistent with the area subjected to quadrant laser photocoagulation. Quadrant laser photocoagulation can have limited efficacy for ameliorating vortex vein congestion in CSC. When laser photocoagulation to the macular area is combined with quadrant laser photocoagulation, attention must be paid to the possible development of CNV and visual field deterioration.

Longitudinal Quantitative Ultrawide-field Fluorescein Angiography Dynamics in the RUBY Diabetic Macular Edema Study

The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional outcomes and spectral domain-OCT metrics. This study is a post hoc analysis of the phase II RUBY study: a prospective, randomized trial of patients with diabetic macular edema (DME) treated with either intravitreal aflibercept injection (IAI) or combined IAI/nesvacumab (antiangiopoietin 2 mAb). Subjects with DME that underwent UWFA across all treatment groups (n= 44). A machine learning-enabled feature extraction system generated panretinal quantitative UWFA metrics, including leakage, ischemia, and microaneurysm (MA) burden. Zonal assessments were performed corresponding to the macula, midperiphery, and far periphery. Changes in ischemic area and index (proportion of nonperfusion in analyzable retina), leakage area and index (proportion of leakage in analyzable retina), and MA count at baseline, week 12, week 24, and week 36 were analyzed. Spectral-domain-OCT quantitative metrics, such as central subfield thickness, ellipsoid zone (EZ) integrity parameters, intraretinal fluid (IRF) volume, and subretinal fluid (SRF) volume were extracted via a machine learning-enhanced OCT feature extraction platform and analyzed. Additionally, the effect of these changes on best-corrected visual acuity (BCVA) was evaluated. Mean panretinal leakage index, zonal leakage area, and panretinal MA count improved significantly between baseline and week 36. Panretinal ischemic index decreased between baseline and week 36, with some aspects showing significant improvement. Mean BCVA significantly improved from baseline to week 36. There was a significant inverse correlation between change in BCVA and change in macular leakage area. A direct correlation was observed between both baseline macular leakage area and panretinal leakage index with IRF volume, SRF volume, and EZ disruption on OCT. Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numeric reduction in panretinal ischemic index and area was noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary end point. Proprietary or commercial disclosure may be found after the references.

CLINICAL IMPLICATION OF RETINAL NERVE FIBER LAYER SCHISIS AND MACULAR FLUORESCEIN LEAKAGE IN PRIMARY IDIOPATHIC EPIRETINAL MEMBRANE.

We evaluated the relationship between macular fluorescein leakage and retinal nerve fiber layer (RNFL) schisis and investigated the visual prognostic values after pars plana vitrectomy (PPV) and idiopathic epiretinal membrane removal. We analyzed the correlations between preoperative optical coherence tomography (OCT) parameters and macular leakage. The final best-corrected visual acuity and central macular thickness were compared according to the presence or absence of macular leakage and RNFL schisis. In 80 eyes with idiopathic epiretinal membrane treated with PPV and membrane peeling, preoperative macular leakage was associated with the presence of preoperative RNFL schisis and inner nuclear layer microcysts. Eyes with both macular leakage and RNFL schisis showed worse postoperative best-corrected visual acuity than those without both factors. In the presence of macular fluorescein leakage and RNFL schisis, postoperative best-corrected visual acuity is worse, and improvements in the central macular thickness are greater than those in the absence of both factors.

Multifocal electroretinographic findings in angiographic macular leakage in the setting of intermediate, posterior, or panuveitis

ObjectifÉvaluer les retombées fonctionnelles de l'exsudat maculaire visible à l'angiographie en l'absence de liquide intrarétinien lors de la tomographie par cohérence optique (OCT) dans des yeux présentant une uvéite intermédiaire, une uvéite postérieure ou encore une panuvéite. MéthodesIl s'agit d'une étude rétrospective portant sur des patients qui ont reçu un diagnostic d'uvéite intermédiaire, d'uvéite postérieure ou encore de panuvéite. Ont été inclus les patients qui ont fait l'objet d'une angiographie à la fluorescéine, d'une OCT et d'une électrorétinographie multifocale (ERGmf) selon un échéancier déterminé. Les données démographiques et cliniques comprenaient le type d'inflammation oculaire, la meilleure acuité visuelle corrigée (MAVC) et les résultats de l'OCT, de l'angiographie à la fluorescéine et de l'ERGmf. Les patients ont été répartis en 2 groupes en fonction de la présence d'un exsudat maculaire visible à l'angiographie et d'un œdème maculaire: groupe 1 (aucun œdème maculaire ni exsudat maculaire) et groupe 2 (présence d'un exsudat maculaire sans œdème maculaire). RésultatsAu total, 29 patients (43 yeux) ont été inclus dans l’étude : 13 patients (17 yeux) dans le groupe 1 et 16 patients (26 yeux) dans le groupe 2. On n'a pas noté de différence statistiquement significative entre les 2 groupes au chapitre des paramètres suivants : âge, sexe, cellules de la chambre antérieure, état du cristallin, cellules du vitré, flou vitréen, MAVC ou épaisseur sous-fovéale centrale moyenne. Aucune des mesures obtenues à l'ERGmf, notamment l'amplitude et les temps de culmination des ondes N1 et P1 dans les anneaux 1–5, n'a différé de manière statistiquement significative entre les 2 groupes. Enfin, aucune corrélation n'a pu être établie entre la MAVC ou l’épaisseur sous-fovéale centrale moyenne et l'une ou l'autre des mesures obtenues à l'ERGmf pour les anneaux 1–3. ConclusionsDans des yeux atteints d'uvéite exempts d’œdème maculaire, l'atteinte de la fonction maculaire n'est pas nécessairement pire en présence d'un exsudat maculaire visible à l'angiographie.

Quantitative analysis of ultra-widefield fluorescein angiography in uveitis associated with sarcoidosis

PurposeTo quantitatively assess the angiographic features of uveitis associated with sarcoidosis on ultra-widefield fluorescein angiography (UWFA) and determine their correlations with clinical features. DesignA retrospective cohort study. MethodsSixty-four eyes (64 patients) with sarcoidosis uveitis were included. On UWFA, presence of vasculitis, macular leakage, and optic disc leakage were assessed and features including peripheral ischemic area, vascular leakage area, and punched out lesions were quantitatively analyzed using FIJI (ImageJ2) and correlated with clinical features. ResultsThe mean peripheral ischemic area and leakage area were 0.0419 ± 0.113% and 0.0333 ± 0.0287% of the total retinal area, respectively. Macular and optic disc leakage were present in 18.8% and 59.4% of eyes, respectively. The average number of punched out lesions was 10.02 ± 21.95. Those changes were most abundant in the inferotemporal area. The presence of disc leakage correlated with all the other UWFA parameters (all r ≥ 0.260; all P ≤ 0.038). The leakage area correlated with vitreous cells, baseline and 6-month logMAR visual acuity, steroid dose and duration, erythrocyte sedimentation rate, and C-reactive protein (r = 0.472, 0.288, 0.321, 0.374, 0.250, 0.251, and 0.277; all P ≤ 0.46). ConclusionsThis study quantitatively analyzed UWFA data in sarcoidosis uveitis. Angiographic changes were most frequent in the inferotemporal area. UWFA parameters correlated with one another and clinical variables. These quantitative imaging results warrant a subjective analysis of sarcoidosis uveitis.

Non-cystic macular thickening on optical coherence tomography as an alternative to fluorescein angiography for predicting retinal vascular leakage in early stages of uveitis

To evaluate the relationship between non-cystic thickening of the macula on optical coherence tomography (OCT) and retinal vascular leakage on fluorescein angiogram (FA) in patients with uveitis. A cross-sectional study of patients seen in the uveitis clinic. Patients with any degree of inflammatory cells in the anterior vitreous were included, provided that no macular cyst or subretinal fluid or macular atrophy was observed in OCT. The correlation between OCT features and best corrected visual acuity (BCVA), the degree of inflammation, and FA findings were examined. The severity of vascular leakage in FA was graded for optic nerve, macula and posterior and peripheral leakage. We used generalized estimation equation to assess the associations between macular thickness and volume with angiographic scores. A total of 43 patients (100 exam data) met inclusion criteria. There was a significant relationship between OCT parameters (central macular thickness, 3 mm and 6 mm perifoveal macular thickness as well as total and central macular volume) with angiographic scores (macular, optic disc, posterior and peripheral vascular leakage score) (all P values < 0.0001). The correlation between the 6 mm perifoveal thickness and peripheral vascular leakage score (R = 0.76; P < 0.001) was stronger than the correlation of CMT with this angiographic score (R = 0.69; P < 0.001). Non-cystic thickening of the macula on OCT, especially in perifoveal area, is a reliable predictor of the presence of retinal vascular leakage in patients with uveitis.

Segmentation of macular neovascularization and leakage in fluorescein angiography images in neovascular age-related macular degeneration using deep learning

Background/objectivesWe aim to develop an objective fully automated Artificial intelligence (AI) algorithm for MNV lesion size and leakage area segmentation on fluorescein angiography (FA) in patients with neovascular age-related macular degeneration (nAMD).Subjects/methodsTwo FA image datasets collected form large prospective multicentre trials consisting of 4710 images from 513 patients and 4558 images from 514 patients were used to develop and evaluate a deep learning-based algorithm to detect CNV lesion size and leakage area automatically. Manual segmentation of was performed by certified FA graders of the Vienna Reading Center. Precision, Recall and F1 score between AI predictions and manual annotations were computed. In addition, two masked retina experts conducted a clinical-applicability evaluation, comparing the quality of AI based and manual segmentations.ResultsFor CNV lesion size and leakage area segmentation, we obtained F1 scores of 0.73 and 0.65, respectively. Expert review resulted in a slight preference for the automated segmentations in both datasets. The quality of automated segmentations was slightly more often judged as good compared to manual annotations.ConclusionsCNV lesion size and leakage area can be segmented by our automated model at human-level performance, its output being well-accepted during clinical applicability testing. The results provide proof-of-concept that an automated deep learning approach can improve efficacy of objective biomarker analysis in FA images and will be well-suited for clinical application.

Predictive Assessment of Quantitative Ultra-Widefield Angiographic Features for Future Need for Anti-VEGF Therapy in Diabetic Eye Disease

The objective of this study was to identify biomarkers that predict a future need for anti-VEGF therapy in diabetic retinopathy (DR). Eyes with DR that underwent ultra-widefield angiography (UWFA) and had at least a 1 year follow-up were grouped based on future anti-VEGF treatment requirements: (1) not requiring treatment, (2) immediate treatment (within 3 months of UWFA), and (3) delayed treatment (after 3 months of UWFA). Quantitative UWFA features and clinical factors were evaluated. Random forest models were built to differentiate eyes requiring immediate and delayed treatment from the eyes not requiring treatment. A total of 173 eyes were included. The mean follow-up was 22 (range: 11–43) months. The macular leakage index, panretinal leakage index, presence of DME, and visual acuity were significantly different in eyes requiring immediate (n = 38) and delayed (n = 34) treatment compared to eyes not requiring treatment (n = 101). Random forest model differentiating eyes requiring immediate treatment from eyes not requiring treatment demonstrated an AUC of 0.91 ± 0.07. Quantitative angiographic features have potential as important predictive biomarkers of a future need for anti-VEGF therapy in DR and may serve to guide the frequency of a follow-up.