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

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

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

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

Predictive Factors and Management of Macular Edema after Retropupillary Iris-Claw Intraocular Lens Implantation in Aphakia: National Multicenter Audit-Report 2.

The aim of this multicenter, national clinical audit is to evaluate the predictive factors and management of postoperative macular edema (ME) after retropupillary iris-claw intraocular lens (RICI) implantation and pars plana vitrectomy (PPV). Preoperative, surgical and postoperative data were collected. Number and type of intravitreal injections (IT) administered (anti-VEGF or dexamethasone implant), visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) assessed by OCT were collected at 1, 3, 6 and 12 months. From 325 eyes (325 patients), 11.7% (38/325) developed postoperative ME. Previous complicated cataract surgery with no capsular support was the only significant predictive factor for developing postoperative ME (OR 2.27, 95% CI 1.38-4.52, p = 0.02) after RICI implant. Mean time to ME development was 11.4 ± 10.7 weeks, and mean CRT peaked at 3 months follow-up. Different treatment options were non-steroidal anti-inflammatory (NSAIDs) drops (31.6%, 12/38), dexamethasone (DEX) implant (50%, 19/38), anti-VEGF (7.9%, 3/38) or combined IT (10.5%, 4/38). Cumulative probability of ME resolution was higher in the group treated with IT than in the group treated with topical NSAIDs (85.2% vs. 58.3%, p = 0.9). Performing RICI implantation after complicated cataract surgery is a risk factor for the development of postoperative ME. DEX implants may be an effective treatment for postoperative ME in these cases.

Radiomics-Based Assessment of OCT Angiography Images for Diabetic Retinopathy Diagnosis.

Purpose: To evaluate the diagnostic accuracy of machine learning (ML) techniques applied to radiomic features extracted from OCT and OCT angiography (OCTA) images for diabetes mellitus (DM), diabetic retinopathy (DR), and referable DR (R-DR) diagnosis. Design: Cross-sectional analysis of a retinal image dataset from a previous prospective OCTA study (ClinicalTrials.govNCT03422965). Participants: Patients with type 1 DM and controls included in the progenitor study. Methods: Radiomic features were extracted from fundus retinographies, OCT, and OCTA images in each study eye. Logistic regression, linear discriminant analysis, support vector classifier (SVC)-linear, SVC-radial basis function, and random forest models were created to evaluate their diagnostic accuracy for DM, DR, and R-DR diagnosis in all image types. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) mean and standard deviation for each ML model and each individual and combined image types. Results: A dataset of 726 eyes (439 individuals) were included. For DM diagnosis, the greatest AUC was observed for OCT (0.82, 0.03). For DR detection, the greatest AUC was observed for OCTA (0.77, 0.03), especially in the 3 × 3 mm superficial capillary plexus OCTA scan (0.76, 0.04). For R-DR diagnosis, the greatest AUC was observed for OCTA (0.87, 0.12) and the deep capillary plexus OCTA scan (0.86, 0.08). The addition of clinical variables (age, sex, etc.) improved most models AUC for DM, DR and R-DR diagnosis. The performance of the models was similar in unilateral and bilateral eyes image datasets. Conclusions: Radiomics extracted from OCT and OCTA images allow identification of patients with DM, DR, and R-DR using standard ML classifiers. OCT was the best test for DM diagnosis, OCTA for DR and R-DR diagnosis and the addition of clinical variables improved most models. This pioneer study demonstrates that radiomics-based ML techniques applied to OCT and OCTA images may be an option for DR screening in patients with type 1 DM. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Herpetic Anterior Uveitis Multicentre Longitudinal Study (The UVHER Project). Baseline Characteristics.

PURPOSE: The aim of the UVHER project is to evaluate the risk of development of optic nerve damage in patients with herpetic anterior uveitis (AU) prospectively followed over 2 years. Herein, we described the baseline characteristics. METHODS: This is a multicentre, prospective study. An aqueous humour tap was performed. Only patients with a positive PCR were included. Clinical characteristics, optical coherence tomography (OCT) parameters and visual field (VF) abnormalities were registered. RESULTS: 27 patients were included: 18 Herpes Simplex (HSV), one Varicella Zoster (VVZ), and 8Cytomegalovirus (CMV). Patients with HSV-AU had severe inflammation, iris atrophy and corneal involvement. In patients with CMV-AU, less inflammation and medium-to-large keratic precipitates were observed. OCT showed a thinner RNFL and GCL in CMV-AU patients in comparison to HSV patients. VF showed abnormalities in six cases. CONCLUSIONS: Patients in the UVHER cohort showed the typical clinical manifestations of herpetic AU. In CMV patients, optic nerve damage was observed at baseline, and in HSV patients, inflammation was more severe.

Vitrectomized vs non-vitrectomized eyes in DEX implant treatment for DMO-Is there any difference? the VITDEX study.

OBJECTIVE: We aimed to compare visual and anatomical outcome in vitrectomized and non-vitrectomized eyes treated with dexamethasone (DEX) implant due to diabetic macular oedema (DMO). DESIGN: Multicenter, retrospective, interventional study. PARTICIPANTS: 236 eyes from 234 patients with DMO with or without previous vitrectomy performed with follow-up of 12 months. METHODS: Records were reviewed for cases of DMO treated with DEX implant in vitrectomized and not vitrectomized eyes. Best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) were recorded at baseline and 12 months after treatment with DEX implants. Correlations between vitreous status and visual and anatomical outcome, as well as safety profile were analysed. MAIN OUTCOME MEASURES: BCVA and CST over follow-up period. SECONDARY OUTCOMES: cataract rate formation, intraocular pressure increase, number of implants needed. RESULTS: The non-vitrectomized group included 130 eyes (55.1%), the vitrectomized group included 106 eyes (44.9%). The groups were well balanced for age and gender (p = 0.540, and p = 0.053, respectively). Both groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no significant difference between the groups in terms of change in vision (p = 0.89) and anatomy (p = 0.65). The mean number of DEX implants given during follow-up was 3.5 in both groups, and there was no significant difference between the groups (p = 0.81). CONCLUSION: We demonstrated similar anatomical and functional efficacy of DEX implant in non-vitrectomized and vitrectomized eyes. Its efficacy was not influenced by full vitrectomy for diabetic retinopathy complications. Safety profile was well balanced between groups.

Paracentral acute middle maculopathy after uneventful ocular surgery with local anaesthetic blocks.

OBJECTIVE: To describe the role of local anaesthetic blocks as a potential cause of paracentral acute middle maculopathy (PAMM) after uneventful ocular surgery. METHODS: Retrospective, observational, international, multicentre case series. Nine cases of PAMM with associated visual loss following uneventful ocular surgery with local anaesthetic blocks were observed in a 9-year period (2011-2020). Demographic, ocular and systemic data, anaesthetic data and surgical details were collected. Visual acuity (VA), fundus photography, fluorescein angiography, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images were reviewed. RESULTS: All nine cases were associated with decreased VA at 24 h postoperative check (ranging from hand movement to 20/200). A hyperreflective band within the middle retinal layers was observed in the structural OCT in the acute phase, evolving to thinning and atrophy of the inner retinal layers in sequential follow-up scans performed. Fluorescein angiography showed delayed perfusion in early arterial phase with normal perfusion in late venous phases. OCTA showed decreased perfusion in the deep capillary plexus. Visual recovery was variable between cases during follow-up (ranging from count fingers to 20/20). CONCLUSIONS: A combination of a vasoconstrictive effect of the anaesthetic agent, an intraocular pressure spike and a mechanical effect of the volume of anaesthetic injected may result in decreased retinal artery perfusion and be evidenced as PAMM in OCT scans. PAMM may present as a potential complication of local anaesthetic blocks in cases of unexpected visual loss after uneventful ocular surgery.

Optical coherence tomography (OCT) angiolytics: a review of OCT angiography quantitative biomarkers.

Optical coherence tomography angiography (OCTA) provides a non-invasive method to obtain angiography of the chorioretinal vasculature leading to its recent widespread adoption. With a growing number of studies exploring the use of OCTA, various biomarkers quantifying the vascular characteristics have come to light. In the current report, we summarize the biomarkers currently described for retinal and choroidal vasculature using OCTA systems and the methods used to obtain them. Further, we present a critical review of these methods and key findings in common retinal diseases and appraise future directions, including applications of artificial intelligence in OCTA .

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 4: Glycated Haemoglobin.

The purpose of this study was to evaluate specifically the relationship between glycated haemoglobin (HbA1c) levels and retinal optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in type 1 Diabetes Mellitus (DM). A total of 478 type 1 DM patients and 115 controls were included in a prospective OCTA trial (ClinicalTrials.gov NCT03422965). Subgroup analysis was performed for controls, no diabetic retinopathy (DM-no DR) and DR patients (DM-DR), and HbA1c levels. OCT and OCTA measurements were compared with HbA1c levels (current and previous 5 years). DM-no DR patients with HbA1c levels >7.5% showed lower VD than DM-DR and controls (20.16 vs. 20.22 vs. 20.71, p < 0.05), and showed a significant correlation between HbA1c levels and FAZc (p = 0.04), after adjusting for age, gender, signal strength index, axial length, and DM disease duration. DM-DR patients with HbA1c > 7.5% presented greater CRT than DM-no DR and controls (270.8 vs. 260 vs. 251.1, p < 0.05) and showed a significant correlation between HbA1c and CRT (p = 0.03). In conclusion, greater levels of HbA1c are associated with OCTA changes in DM-no DR patients, and with structural OCT changes in DM-DR patients. The combination of OCTA and OCT measurements and HbA1c levels may be helpful to identify patients at risk of progression to greater stages of the diabetic microvascular disease.

Simultaneous pars plana vitrectomy, panretinal photocoagulation, cryotherapy, and Ahmed valve implantation for neovascular glaucoma.

AIM: To describe and evaluate the efficacy of Ahmed glaucoma valve implantation (AGV) combined with pars plana vitrectomy (PPV) in a single surgical act for the treatment of advanced neovascular glaucoma (NVG). METHODS: Retrospective observational case series included 51 eyes from 50 patients with severe NVG treated with PPV, AGV, and panretinal photocoagulation and/or cryotherapy in a single surgical act during a 13-year period (2005-2018). Preoperative, intraoperative and postoperative data at day 1 and months 1, 3, 6, 21, and 24 were systematically collected. Definition of surgical success was stablished at IOP between 6 and 21 mm Hg with or without topical treatment. RESULTS: Main indications for surgery were NVG secondary to proliferative diabetic retinopathy (39.2%) and central retinal vein occlusion (37.3%). Mean (±SD) preoperative IOP was 42.0±11.2 mm Hg decreasing to 15.5±7.1 mm Hg at 12mo and 15.8±9.1 mm Hg at 24mo of follow up. Cumulative incidence of success of IOP control was 76.0% at first postoperative month, reaching 88.3% at 6mo. Prevalence of successful IOP control at long term was 74.4% at 12mo and 71.4% at 24mo. Eye evisceration for unsuccessful NVG management was required in 1 case (2.0%). CONCLUSION: Combination of AGV implantation and PPV in a single act may be a suitable option for severe forms of NVG in a case-by-case basis for effective IOP control and a complete panretinal photocoagulation.

Late Onset Macular Oedema in a Patient with Multiple Sclerosis Treated with Fingolimod.

Macular oedema is a rare complication of fingolimod treatment. It usually presents within 3-4 months, but occasionally presents later. It can resolve without treatment despite continuation of fingolimod treatment. Herein we report a case of very late onset macular oedema in a 49-year-old woman with multiple sclerosis treated with fingolimod for 7 years. The patient presented with blurred vision in both eyes with visual acuities of 20/32 in her right eye and 20/25 in her left eye. She had macular oedema, that without discontinuing fingolimod treatment, resolved after 1 month.

RETROPUPILLARY IRIS-CLAW INTRAOCULAR LENS AND PARS PLANA VITRECTOMY IN APHAKIA MANAGEMENT: A National Multicenter Audit.

PURPOSE: To evaluate the outcomes and safety of retropupillary iris-claw intraocular lens implantation and associated pars plana vitrectomy. METHODS: Multicenter, national audit of 325 eyes (325 patients). Demographics, surgical details, and complications are described. Visual acuity, intraocular pressure, and central retinal thickness assessed by optical coherence tomography were collected at 1, 3, 6, and 12 months after surgery. Kaplan-Meier curves were created to assess the cumulative probability of postoperative visual acuity and intraocular pressure levels, macular edema development, and corneal decompensation. RESULTS: The cumulative probability of the final visual acuity ≤0.3 logarithm of the minimum angle of resolution (≥20/40 Snellen) was 75.6% at 12-month follow-up. The probability of intraocular pressure >21, ≥25, and ≥30 mmHg was 48.1%, 33.1%, and 19.0%, and the probability of intraocular pressure-lowering drops was 50.9% at 12 months. Glaucoma surgery was required in 4.3% of the eyes (14/325). The cumulative probability of macular edema was 20.5% at 12 months and was greater in complicated cataract surgery than in intraocular lens-luxation eyes (26% vs. 16.7%, P = 0.04). Corneal transplantation was required in 2.8% of the eyes (9/325). CONCLUSION: This study on 325 eyes with aphakia or intraocular lens dislocation managed with the retropupillary iris-claw intraocular lens technique provides clinical outcomes in a real-world scenario, reporting relevant data for patient counseling and preoperative discussions.

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus-Report 2: Diabetic Kidney Disease.

The purpose of this study is to investigate potential associations between optical coherence tomography angiography (OCTA) parameters and diabetic kidney disease (DKD) categories in type 1 diabetes mellitus (T1DM) patients and controls. A complete ocular and systemic examination, including OCTA imaging tests and bloods, was performed. OCTA parameters included vessel density (VD), perfusion density (PD), foveal avascular zone area (FAZa), perimeter (FAZp) and circularity (FAZc) in the superficial vascular plexus, and DKD categories were defined according to glomerular filtration rate (GFR), albumin-creatinine ratio (ACR) and KDIGO prognosis risk classifications. A total of 425 individuals (1 eye/1 patient) were included. Reduced VD and FAZc were associated with greater categories of GFR (p = 0.002, p = 0.04), ACR (p = 0.003, p = 0.005) and KDIGO risk prognosis classifications (p = 0.002, p = 0.005). FAZc was significantly reduced in greater KDIGO prognosis risk categories (low risk vs. moderate risk, 0.65 ± 0.09 vs. 0.60 ± 0.07, p < 0.05). VD and FAZc presented the best diagnostic performance in ROCs. In conclusion, OCTA parameters, such as VD and FAZc, are able to detect different GFR, ACR, and KDIGO categories in T1DM patients and controls in a non-invasive, objective quantitative way. FAZc is able to discriminate within T1DM patients those with greater DKD categories and greater risk of DKD progression.

Differential response to intravitreal dexamethasone implant in naïve and previously treated diabetic macular edema eyes.

BACKGROUND: To identify different response patterns to intravitreal dexamethasone implants (IDI) in naïve and previously treated (PT) diabetic macular edema (DME) eyes in a real-life setting. METHODS: 342 IDI injections (203 DME eyes) were included. Number of IDI injections, percentage (%) of eyes with 1, 2, 3 and ≥ 4 injections, time to reinjections, visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) were evaluated for naïve and PT DME eyes over 24 months. RESULTS: Mean number of injections was significantly lower in naïve vs PT DME eyes (1.40 ± 0.9 vs 1.82 ± 0.9, p < 0.001). The percentage of eyes receiving 1 injection was significantly higher in naïve vs PT DME eyes (76.1 vs 47.7), (p < 0.001). However, it was significantly lower for 2 (16.4 vs 29.4), or 3 injections (1.4 vs 17.6) (both p < 0.001), with no differences in eyes receiving ≥4 injections (5.9 vs 5.1 respectively, p = 0.80). Mean time to reinjection was not significantly different between both groups for the second, third and fourth injection (9.6 ± 4.0 vs 10.0 ± 5.5, p = 0.75, 13.2 ± 4.0 vs 16.0 ± 3.5, p = 0.21 and 21.7 ± 3.8 vs 19.7 ± 5.8, p = 0.55). VA scores were consistently better in naïve vs PT DME eyes at all studied timepoints, with no significant differences in CRT reduction or adverse effect rates. CONCLUSION: Naïve DME eyes received lower number of IDI injections and showed better VA levels than PT DME eyes for 24 months in a real-world setting. This data supports the IDI use in early DME stages and provide further evidence of better IDI response when used as first-line therapy.

Predictive capacity of baseline hyperreflective dots on the intravitreal dexamethasone implant (Ozurdex®) outcomes in diabetic macular edema: a multicenter study.

PURPOSE: The purpose of this study is to evaluate the predictive capacity of the baseline hyperreflective dots (HRDs) on the functional and anatomical response in patients with diabetic macular edema (DME). Additionally, we assessed the impact of the intravitreal dexamethasone (DEX) implant on the functional and anatomic outcomes. METHODS: Retrospective, multicenter study. The number of HRDs was graded in four different stages: [A] none HRDs; [B] few, 1-10 HRDs; [C] moderate, 11-20 HRDs; and [D] many, ≥ 21 HRDs. For statistical purposes, groups A and B were combined [scarce HRDs (S-HRDs)] and group D was renamed as [abundant HRDs (A-HRDs)]. The primary endpoints were the mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) according to baseline HRD stage. RESULTS: One hundred eyes from one hundred patients were included in the study. Mean BCVA significantly improved from 52.9 (50.0 to 55.8) letters ETDRS at baseline to 57.2 (54.0 to 60.4) letters at month 6, p = 0.0039. There were no significant differences between the S-HRDs and A-HRD study groups in BCVA. As compared to baseline, CMT reduction was 106.3 (59.8 to 152.7) µm and 94.2 (34.7 to 153.7) µm in S-HRDs and A-HRD groups, respectively (p < 0.0001 each, respectively). Twenty-three (65.7%) and 18 (62.1%) eyes achieved a CMT reduction ≥ 10% in the S-HRD and A-HRD groups, respectively, p = 0.7640. DEX implant significantly reduced the presence of outer nuclear layer (ONL) disruptions (p = 0.0010). CONCLUSIONS: The number of HRDs did not influence either functional or anatomic outcomes. DEX implant significantly decreases the number of eyes with ONL disruptions, which might improve retinal integrity.