Preclinical ocular changes in systemic lupus erythematosus patients by optical coherence tomography.

OBJECTIVE: The aim of the present study was to detect preclinical changes in SLE patients in retinal microvascularization or retinal and optical nerve structure by optical coherence tomography. METHODS: This cross-sectional, single-centre study aimed to describe structural changes [macular and retinal nerve fibre layer (RNFL) thickness] by structural spectral-domain optical coherence tomography (SD-OCT) and perifoveal vascular [vessel density (VD) and vascular perfusion (VP) and foveal avascular zone (FAZ) structural parameters] findings by OCT angiography (OCTA) in 78 SLE patients and 80 healthy volunteers. In addition, we analysed their association with clinical and laboratory parameters, medications received, disease duration, and SLE activity and damage. RESULTS: Structural parameters by SD-OCT and perifoveal vascular parameters by OCTA were decreased in SLE patients compared with controls. OCTA parameters (VD, VP and FAZ circularity) and macular thickness were also decreased in patients with longer disease duration (>10 years). The presence of aPLs was associated with a decreased RNFL thickness, mainly in the inferior quadrants. Patients developing APS also showed decreased RNFL thickness and OCTA flow changes. SD-OCT and OCTA results were not associated with disease activity. Foveal structural parameters were lower in patients with higher damage score. CONCLUSION: SD-OCT and OCTA can detect preclinical structural and microcirculatory changes in SLE patients. Structural and perifoveal vascular macular changes in SLE patients are related to disease duration. Macular structural parameters were impaired in patients with higher disease damage. APS seems to be associated with preclinical damage to the optic nerve and impairment of the perifoveal microvasculature.

Progression of Retinal Ganglion Cell and Nerve Fiber Layer Loss in Spinocerebellar Ataxia 3 Patients.

Spectral domain optical coherence tomography (SD-OCT) allows noninvasive measurements of retinal neuron layers. Here, we evaluate the relationship between clinical features and anatomical SD-OCT measurements in patients with spinocerebellar ataxia type 3 (SCA3) and how they change with time. A retrospective review was conducted on SCA3 patients. Clinical variables such as disease duration, number of CAG repeats, and the Scale for the Assessment and Rating of Ataxia (SARA) score were correlated with SD-OCT measurements, including retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, macular volume (MV), and central macular thickness (CMT). Seventeen SCA3 patients with an average follow-up of 44.9 months were recruited. Clinical features with significant baseline correlations with SD-OCT measurements included disease duration (CMT r = - 0.590; GCC r = - 0.585), SARA score (CMT r = - 0.560; RNFL r = - 0.390), and number of CAG repeats (MV r = - 0.552; RNFL r = - 0.503; GCC r = - 0.493). The annual rate of change of the SARA score during follow-up was associated with that of both the MV (r = - 0.494; p = 0.005) and GCC thickness (r = - 0.454; p = 0.012). High disability (stages 2 and 3) was independently inversely associated with the annual change in MV (ß coefficient - 17.09; p = 0.025). This study provides evidence of an association between clinical features and objective anatomical measurements obtained by SD-OCT in SCA3 patients. MV and GCC thickness could serve as potential biomarkers of disease severity, as their rates of decrease seem to be related to a worsening in the SARA score. These findings highlight the potential of SD-OCT as a noninvasive tool for assessing disease severity and progression in SCA3 patients.

Altered retinal structure and function in Spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice. We evaluated the retinal structure and function in five patients with SCA3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using optical coherence tomography (OCT) and electroretinogram (ERG). In the transgenic mice, we further: a) determined the retinal expression pattern of ATXN3 and the distribution of cones and rods using immunofluorescence (IF); and b) assessed the retinal ultrastructure using transmission electron microscopy (TEM). Some patients with SCA3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and showed further thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli. Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with SCA3.

Creation of a neovascular age-related macular degeneration national database using a web-based platform: Fight Retinal Blindness Spain. Report 1: Visual outcomes.

BACKGROUND: To study the visual outcomes of neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs at national level. METHODS: Multicenter national database of nAMD eyes treated with anti-VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat-and-extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!). RESULTS: 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p = 0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/-3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p = 0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p = 0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%). CONCLUSION: Independent, large-scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real-world international cohorts.

Systemic contribution of inflammatory mediators to the severity of diabetic and uveitic macular edema.

PURPOSE: To assess whether serum cytokine and growth factor levels are associated with diabetic macular edema (DME) and uveitic macular edema (UME) objective severity. METHODS: Cross-sectional observational study of 81 patients (1 eye/patient) with DME (n=48) and UME (n=33). Macular edema (ME) was defined upon central macular thickness (CMT) ≥ 300 µm on spectral domain optical coherence tomography (OCT). Serum samples were obtained from peripheral blood and IL-1ß, IL-6, IL-8, IL-10, MCP-1, TNF-α, and VEGF levels were determined by Luminex analysis. Main outcome measure was the correlation between mediators' levels and CMT and macular volume (MV) on OCT for ME cases. RESULTS: In DME, IL-6 levels were found to significantly correlate with MV (r=0.324; p=0.028) whereas in UME, IL-8 was significantly associated with both CMT (r=0.401; p=0.021) and MV (r=0.391; p=0.024). IL-8 independently correlated with CMT (ß=177.2; p=0.033) and MV (ß=3.17; p=0.008) in UME multivariate model. CONCLUSION: Peripheral blood IL-6 and IL-8 levels could play a role in the severity of DME and UME, respectively. IL-8 even seems to be independently associated with CMT and MV in UME cases. Such systemic implications could enforce DME and UME personalized diagnostic and therapeutic approaches.

Treat-and-extend versus fixed bimonthly treatment regimens for treatment-naive neovascular age-related macular degeneration: real world data from the Fight Retinal Blindness registry.

PURPOSE: To compare the outcomes of two different antivascular endothelial growth factor treatment regimens for treatment-naive eyes with neovascular age-related macular degeneration in routine clinical care at 12 and 24 months in Spain. METHODS: Observational study using the Fight Retinal Blindness (FRB) outcomes registry platform. Eyes were treated with fixed bimonthly (FB) aflibercept group at one center and a treat-and-extend (TAE) regimen using either aflibercept or ranibizumab at the other center. RESULTS: We included 192 eyes. Of these, 160 eyes (83%) completed 12 months (86 TAE and 74 FB) and 79 (41%) completed 24 months (46 for TAE and 33 for FB) of follow-up. No statistically significant differences (p > 0.05) were found regarding mean visual acuity (VA, logMAR letters) at baseline (12 month cohort TAE 59.6 vs FB 57.9; 24 month cohort TAE 61.7 vs FB 62.6), final mean VA (12 month cohort TAE 61.1 vs FB 63.0; 24 month cohort TAE 64.8 vs FB 66.4), and median number of injections (12 months TAE 7 vs FB 7; 24 months TAE 11 vs FB 12). However, the distribution of injection frequencies for the TAE group was larger, with 35% of TAE eyes receiving ≤ 6 injections at 12 months compared with only 19% of FB eyes (p = 0.024). CONCLUSION: Similar VA results were observed with TAE and FB regimens, with no differences in the median number of injections. However, the TAE approach seemed to deliver a wider distribution of injection frequencies due to its individualized approach, which may help reduce the burden of injections in some eyes.

Uveitic macular edema response to intravitreal dexamethasone implant is independent of optical coherence tomography findings.

PURPOSE: To identify predictive response optical coherence tomography (OCT) findings in uveitic macular edema (UME) treated with intravitreal dexamethasone implant (DEX). METHODS: Retrospective study of 66 eyes (53 patients) treated with DEX for UME. SD-OCT macular scans were collected prior to DEX treatment and 6 weeks and 3 months after the DEX implant. OCT images were evaluated for qualitative and quantitative characteristics (central retinal thickness, CRT and macular volume, MV). A multivariate analysis of covariance (ANCOVA) was carried out to study the predictive influence of OCT and clinical covariates on outcomes. The main outcome was a composite endpoint based on the simultaneous gain of 5 or more letters associated with a 20% or more reduction in CRT. RESULTS: A significant improvement in BCVA at 6 weeks (mean change from baseline -0.2, SD 0.3) and 3 months (mean -0.2, SD 0.4) was observed after the DEX implant. A significant decrease in CRT (change from baseline -187.7 µm at 3 months) and MV (change from baseline -1.7 mm3 at 3 months) were also observed. An association of ≥ 5-letter improvement in BCVA and a ≥ 20% CRT reduction was observed in 44.6% of cases at 6 weeks and 31.4% at 3 months. ANCOVA multivariate analyses found CRT at 3 months independent from baseline clinical variables but from CRT. CONCLUSION: DEX implant is an effective treatment for UME independently of basal characteristics, producing both a gain of visual acuity and improvement of macular anatomy by OCT measures at 3 months.

Amniotic membrane extract eye drops for ocular surface diseases: use and clinical outcome in real-world practice.

PURPOSE: To study the indications and clinical outcomes, in a real-word setting, of amniotic membrane extract eye drops (AMEED) use for ocular surface disease (OSD). METHODS: A retrospective study of patients treated with topical AMEED between January 2018 and January 2020 was conducted. Patients were classified in two groups according to specific OSD-dry eye disease (DED) and wound healing delay (WHD) groups. Demographics, comorbidities, treatment duration and clinical outcomes were analysed. RESULTS: A total of 50 eyes of 36 patients with or without previous treatments were included. Patients in the DED group presented more systemic comorbidities (83 vs 22%; p < 0.001) and spent more mean time under AMEED treatment (10 vs 7.2 months average) than the WHD group (p = 0.0104). In four patients, long-term treatment (more than 24 months) was reported. Global similar symptomatic improvement was reported for both groups (DED 88.9% vs WHD 100%; p = 0.486), with the WHD group especially consisting in general relief (78%) and the DED group reporting more pain improvement (44%) (p = 0.011). Regarding patients with autologous serum as a previous treatment, no statistical differences were found in subjective or objective improvement. An overall success was achieved in 94.4% of the cases and no adverse events were found. CONCLUSION: AMEED administration is a promising mean to treat OSD such as dry eye, persistent epithelial defect and corneal ulcers. Although AMEED may be effective in the treatment of severe DED and persistent epithelial defect or corneal ulcers, conclusions are limited owing to the absence of controlled clinical trials.

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.

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

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

Current clinical application of sclera and amniotic membrane for ocular tissue bio-replacement.

To report the current clinical applications and trends of scleral and amniotic membrane use in ophthalmology. Review of annual reports from the Catalan Transplant Organization (OCATT), on scleral patch and amniotic membrane eye indications in Catalonia region (Spain) over a 6-year period from 2013 to 2018. A total of 874 scleral and 1665 amniotic membranes patches were implanted, from January 2013 to December 2018. The most frequent indication over the 6-year period for scleral patch was glaucoma surgery (77.5%), eyelid reconstruction (5.2%) and corneal or scleral ulcer (5%). Regarding amniotic membrane, corneal ulcer (26.9%), conjunctival reconstruction (23.8%) and corneal epithelial defect (22.7%) were the most common indications. During the study period, an increasing trend was found on sclera patches for eyelid reconstruction (p = 0.0032) and amniotic membrane for inflammation management (p = 0.0198). Glaucoma surgery and corneal ulcers have represented the top indications for scleral patch and amniotic membrane use, over the period, respectively. A significant trend has also been found towards eyelid reconstruction using scleral patches and amniotic membrane for anterior segment inflammation management. This evolving scenario in tissue use for ocular surgery has to be taken into consideration, especially regarding eye banks facing current and futures changes in tissue preservation, storage and indications.

Shear stress modulates inner blood retinal barrier phenotype.

The vascular endothelium responds to the shear stress generated by blood flow and changes function to maintain tissue homeostasis and adapt to injury in pathological conditions. Shear stress in the retinal circulation is altered in patients with retinal vascular diseases, such as diabetic retinopathy. Therefore, we aimed to study the effect of laminar shear stress on barrier properties and on the release of proinflammatory cytokines in human retinal microvascular endothelial cells (HRMEC). HRMEC were cultured in Ibidi flow chambers and exposed to laminar shear stress (0-50 dyn/cm2) for 24-48 h. Tight junction distribution (ZO-1 and claudin-5) and cytokine production were determined by immunofluorescence and ELISA, respectively. The chemotactic effect of conditioned media exposed to shear stress was determined by measuring lymphocyte transmigration in Transwells. We found that cells exposed to moderately low shear stress (1.5 and 5 dyn/cm2) showed enhanced distribution of membrane ZO-1 and claudin-5 and decreased production of the proinflammatory cytokines IL-8, CCL2, and IL-6 compared to static conditions and high shear stress values. Moreover, conditioned media from cells exposed to low shear stress, had the lowest chemotactic effect to recruit lymphocytes compared to conditioned media from cells exposed to static and high shear stress conditions. In conclusion, high shear stress and static flow, associated to impaired retinal circulation, may compromise the inner blood retinal barrier phenotype and barrier function in HRMEC.

Cockayne syndrome in adults: complete retinal dysfunction exploration of two case reports.

PURPOSE: Cockayne syndrome is a rare autosomal recessive disease, also known as a progeria disorder, causing dwarfism, senile appearance and multiple systemic affections. Ophthalmic abnormalities are frequent, for example, in the forms of pigmentary retinopathy with low visual acuity. We present two genetic-confirmed cases with a detailed electrophysiological exploration of their retinal findings. METHODS: Complete ophthalmic exploration is undertaken, including full-field electroretinogram under ISCEV guidelines and multifocal electroretinogram (RETI-scan science, Roland-Consult, Germany), ultra-wide-field retinography and autofluorescence (Optomap, Optos PLC, Dunfermline, Scotland, UK) and macular and retinal nerve fibre layer optical coherence tomography (Cirrus, Carl-Zeiss Meditec, Inc, Dublin, CA). RESULTS: Both cases presented with CSA/ERCC8 mutation and low visual acuity. Diffuse pigmentary retinopathy with macular atrophy was found in ultra-wide-field retinography and autofluorescence. Electrophysiological testing reported wide retinal dysfunction on both cone and rod system with macular involvement. CONCLUSIONS: Pigmentary retinopathy in CS could translate a wide dysfunction of the retina with major affection of external retinal layers of both cone and rod cells. Macular implication is also present and could explain progressive vision loss in such cases.

Evaluation of microvascular changes in the perifoveal vascular network using optical coherence tomography angiography (OCTA) in type I diabetes mellitus: a large scale prospective trial.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blindness in type 1 Diabetes Mellitus (DM) patients, as a consequence of impaired blood flow in the retina. Optical coherence tomography angiography (OCTA) is a newly developed, non-invasive, retinal imaging technique that permits adequate delineation of the perifoveal vascular network. It allows the detection of paramacular areas of capillary non perfusion and/or enlargement of the foveal avascular zone (FAZ), representing an excellent tool for assessment of DR. The relationship of these microvascular changes with systemic factors such as metabolic control or duration of the disease still needs to be elucidated. METHODS: Prospective, consecutive, large-scale OCTA study. A complete ocular examination including a comprehensive series of OCTA images of different scan sizes captured with 2 OCT devices (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA, USA, and Triton Deep Range Imaging OCT, Topcon Corp, Topcon, Japan) will be obtained as part of the yearly routine follow up visits in type 1 DM patients seen in the Diabetes Unit of the Endocrinology department which give written informed consent to participate in the project. The aim of this study is to investigate the relationship between OCTA-derived parameters and systemic factors, as metabolic control (Hb1Ac, lipid profile, cholesterol, etc), and other relevant clinical factors as demographics or duration of the disease. DISCUSSION: This study is directed to investigate the relationship between the status of the perifoveal vascular network and systemic markers of the disease, and in particular to study whether these changes reflect those occurring elsewhere in the body affected by diabetic microvascular disease, as the kidneys or the brain. If these relationships were demonstrated, early detection of these microvascular changes by OCTA could lead to modifications in the pharmacological management of type 1 diabetic patients, as a way to reduce the risk of future complications in both the eye and other organs. TRIAL REGISTRATION: ClinicalTrials.gov, trial number NCT03422965.

Comparison of intraocular lens tilt after capsular sutured scleral fixation with capsular segments versus uneventful cataract surgery.

PURPOSE: To evaluate and compare intraocular lens (IOL) tilt between uneventful phacoemulsification with in-the-bag IOL implantation and sutured scleral fixation (SSF) of the lens bag with a capsular tension segment (type 6 D / Morcher) using a Sheimpflug camera. SETTING: Clinical Practice, Hospital. Barcelona and A Coruña, Spain. DESIGN: Retrospective, comparative multicenter study. METHODS: IOL tilt was compared between patients who underwent sutured scleral fixation with a capsular tension segment in a single eye (SSF group, n = 15) with patients who underwent uneventful IOL implantation (control group, n = 12) that were matched by biometric measurements. Post-operative refractive accuracy of biometric formulas by means of mean absolute error (MAE) was also reported. All patients underwent a general ophthalmic evaluation, anterior segment photography, and postoperative optical biometry (Zeiss IOLMaster® 500). In addition, IOL tilt was measured with a Scheimpflug camera (Pentacam R, Oculus Optikgerate Gmbh). RESULTS: Mean vertical tilt was similar in both groups (2.20+/-2.47° SSF vs 1.97 +/- 1.79° control; p = 0.836) but mean horizontal tilt tended to higher values in the SSF series (2.09 +/- 2.74° vs 0.94 +/- 1.17°; p = 0.139). Considering post-operative refractive error in diopters by MAE calculations, there was an underestimation of IOL power in the SSF group which was only statistically significant for Barrett Universal II (1.07 vs 0.32; p = 0.028) and Hill-RBF (0.95 vs 0.26; p = 0.024) formulas, but not for SRK/T (0.99 vs 0.42; p = 0.285) and Kane (0.96 vs 0.33; p = 0.083). CONCLUSION: Sutured scleral fixation of capsular tension segments in the presence of zonular instability does not seem to induce clinically significant IOL tilt compared to uneventful cataract extraction cases.

New proposal for a multimodal imaging approach for the subclinical detection of hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

OBJECTIVE: To compare multimodal structural and functional diagnostic methods in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine, to identify the best complementary approach for detecting subclinical retinal toxicity. METHODS: A cross-sectional, unicentric study was conducted on patients with SLE treated with hydroxychloroquine. Each patient underwent a comprehensive ophthalmic evaluation, comprising structural tests (spectral-domain optical coherence tomography (SD-OCT), en face OCT, en face OCT angiography (OCTA), fundus autofluorescence (FAF)) and functional tests (automated perimetry for visual field (VF) testing, multifocal electroretinography (mfERG)). A diagnosis of macular toxicity required the presence of abnormalities in at least one structural and functional test. The Kappa Concordance Index was used to assess the concordance among the different tests in detecting potential macular toxicity-associated alterations. RESULTS: Sixty-six patients with SLE (132 eyes) were consecutively enrolled. Four (6.1%) patients developed subclinical hydroxychloroquine-induced retinal toxicity without visual acuity impairment. The proportion of abnormal results was 24% for both en face OCT and en face OCTA. Regarding functional analysis, VF was less specific than mfERG in detecting subclinical retinal toxicity (VF specificity 47.5%). En face OCT and en face OCTA structural findings showed better concordance, with a kappa index >0.8, and both identified the same cases of toxicity as FAF. CONCLUSION: Although structural OCT and VF are frequently used to screen for hydroxychloroquine-induced retinal toxicity, our findings suggest that a combination of mfERG, en face OCT and en face OCTA could improve the diagnostic accuracy for subclinical retinal damage. This study emphasises the importance of a multimodal imaging strategy to promptly detect signs of hydroxychloroquine-induced retinal toxicity.

C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.

Purpose: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters. Methods: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters. Results: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023). Conclusion: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.

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.