Three-year outcomes of vascular endothelial growth factor inhibitors in naïve branch retinal vein occlusion: Fight Retinal Blindness!

PURPOSE: To evaluate the 3-year outcomes of vascular endothelial growth factor (VEGF) inhibitors in the treatment of cystoid macular oedema (CME) due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. DESIGN: Multicenter, international, BRVO database study. SUBJECTS: Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) letters, central subfield thickness (CST), treatments, number of injections and visits data was collected using a validated web-based tool. MAIN OUTCOME MEASURES: Visual acuity (VA) gain at 3 years in LogMAR letters. Secondary outcome measures included anatomical results, treatment pattern and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. RESULTS: Mean adjusted VA change was +11 letters (95% CI 9,13), mean adjusted change in CST was -176µm (-193, -159). Median number of injections/visits was 16/24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n=677) and as a monotherapy in 71% (n=538). Few eyes were switched to steroids (11%, n=83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs -128 vs -114µm; p< 0.001) and significantly lower switching rates (14% vs 38% vs 33%, p< 0.001) compared with ranibizumab and bevacizumab, respectively. CONCLUSIONS: This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar amongst the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate.

Factors associated with early hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

PURPOSE: Hydroxychloroquine is currently recommended for the treatment of systemic lupus erythematosus (SLE), but it can cause irreversible retinal toxicity. This study aimed to identify factors associated with early hydroxychloroquine-induced retinal toxicity in patients with SLE from a single centre for 20 years. METHODS: SLE patients diagnosed between 1998 and 2017 and followed up for at least 1 year were included. Demographic, clinical, laboratory and therapeutic data were collected from the electronic medical records and retrospectively analysed. Early hydroxychloroquine-induced retinal toxicity was defined as the development of macular toxicity within the first 5 years of hydroxychloroquine treatment. RESULTS: A total of 345 patients followed for a median of 15 years were analysed; 337 (97.7%) patients received hydroxychloroquine, 38 (11.3%) of them presented with retinal toxicity, and 10 (3%) developed early retinal toxicity. These patients had a mean treatment duration of 3.3 years with a mean cumulative dose of 241 g. Patients were diagnosed by visual field (VF) and fundoscopy, and two were also assessed using spectral domain optical coherence tomography (SD-OCT). The median (IQR) age of patients with early toxicity was 56 (51-66) years, and 80% were female. Factors independently associated with early hydroxychloroquine-induced retinal toxicity were lupus anticoagulant positivity (OR 4.2; 95% CI 1.2-15.5) and hypercholesterolaemia (OR 5.6; 95% CI 1.5-21.5). CONCLUSION: Our results suggest that lupus anticoagulant positivity and hypercholesterolaemia among SLE patients may be risk factors for early hydroxychloroquine-induced retinal toxicity, regardless of the dose or duration of treatment.

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.

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.

Corneal Endothelial Cell Cultures from Organotypic Preservation of Older Donor Corneas Are Suitable for Advanced Cell Therapy.

INTRODUCTION: The purpose of this work was to evaluate the in vitro growth capacity and functionality of human corneal endothelial cells (hCEC) expanded from corneas of elderly (>60 years) donors that were preserved using an organotypic culture method (>15 days, 31°C) and did not meet the clinical criteria for keratoplasty. METHODS: Cell cultures were obtained from prior descemetorhexis (≥10 mm) and a controlled incubation with collagenase type I followed by recombinant trypsin. Cells were seeded on coated plates (fibronectin-albumin-collagen I) and cultures were expanded using the dual supplemented medium approach (maintenance medium and growth medium), in the presence of a 10 µm Rho-associated protein kinase inhibitor (Y-27632). Cell passages were obtained at culture confluency (∼2 weeks). A quantitative colorimetric WST-1 cell growth assay was performed at different time points of the culture. Morphometric analysis (area assessment and circularity), immunocytochemistry (ZO-1, Na+/K+-ATPase α, Ki67), and transendothelial electrical resistance (TEER) were performed on confluent monolayers. RESULTS: There was no difference between the cell growth profiles of hCEC cultures obtained from corneas older than 60 years, whether preserved cold or cultivated organotypic corneas. Primary cultures were able to maintain a certain cell circularity index (around 0.8) and morphology (hexagonal) similar to corneal endothelial mosaic. The ZO-1 and Na+/K+-ATPase pump markers were highly positive in confluent cell monolayers at 21 days after isolation (passage 0; P0), but significantly decreased in confluent monolayers after the first passage (P1). A weak expression of Ki67 was observed in both P0 and P1 monolayers. The P0 monolayers showed a progressive increase in TEER values between days 6 and 11 and remained stable until day 18 of culture, indicating a state of controlled permeability in monolayers. The P1 monolayers also showed some functional ability but with decreased TEER values compared to monolayers at P0. CONCLUSIONS: Our results indicate that it is possible to obtain functional hCEC cultures in eye banks, using simplified and standardized protocols, from older donor corneas (>60 years of age), previously preserved under organotypic culture conditions. This tissue is more readily available in our setting, due to the profile of the donor population or due to the low endothelial count (<2,000 cells/mm2) of the donated cornea.

Role of Interferon-Gamma Release Assay for the Diagnosis and Clinical Follow up in Ocular Tuberculosis.

PURPOSE: To assess the performance of interferon-gamma release assay (IGRA) associated with tuberculosis skin test (TST) for ocular tuberculosis (OTB) diagnosis and therapeutic decision making. METHOD: One hundred and ninety-one patients with ocular inflammation were prospectively followed-up. Patients with clinical signs highly suspected of OTB, TST≥10 mm, and/or IGRA≥0.35 IU/mL received antitubercular therapy (ATT). Sensitivity (Se), specificity (Sp), and area under the curve (AUC) were assessed. RESULTS: Seventy-two (37.7%) patients received ATT for presumed OTB. Combining TST and IGRA had Se=89.6%, Sp=99.2%, and AUC (0.98) significantly higher compared to TST (0.85, Z=6.3, p<.001) or IGRA (0.95, Z=2.5, p=.01). Prior history of corticosteroids or immunosuppressant with concomitantly oral prednisone and baseline IGRA> 2.0 IU/mL was associated significantly with more recurrences in ATT patients (p=.01)      . CONCLUSION: Considering TST and IGRA together was more effective in assessing OTB diagnosis. The real value of the IGRA test to predict recurrences needs further studies.

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.

Intraocular pressure after myopic laser refractive surgery measured with a new Goldmann convex prism: correlations with GAT and ORA.

BACKGROUND: The purpose of this study is to describe measurements using a newly developed modified Goldmann convex tonometer (CT) 1 year after myopic laser refractive surgery. Intraocular pressure (IOP) measurements were compared with IOP values obtained by Goldmann applanation tonometer (GAT), and Ocular Response Analyzer (ORA). METHODS: Prospective double-masked study performed on thirty eyes of thirty patients that underwent laser in situ keratomileusis (LASIK; n = 19) or photorefractive keratectomy (PRK; n = 11). IOP was measured before and 3 and 12 months after surgery. Intraclass correlation coefficient (ICC) and Bland-Altman plot were calculated to assess the agreement between GAT, CT, IOPg (Goldmann-correlated IOP) and IOPcc (corneal-compensated IOP) from ORA. RESULTS: Twelve months after LASIK, IOP measured with CT showed the best correlation with IOP measured with GAT before surgery (GATpre) (ICC = 0.886, 95% CI: 0.703-0.956) (15.60 ± 3.27 vs 15.80 ± 3.22; p < 0.000). However, a moderate correlation was found for IOP measured with IOPcc and CT 12 months after LASIK (ICC = 0.568, 95% CI: - 0.185 - 0.843) (15.80 ± 3.22 vs 12.87 ± 2.77; p < 0.004). Twelve months after PRK, CT showed a weak correlation (ICC = - 0.266, 95% CI: - 3.896 - 0.663), compared to GATpre (17.30 ± 3.47 vs 16.01 ± 1.45; p < 0.642), as well as poor correlation (ICC = 0.256, 95% CI: - 0.332 - 0.719) with IOPcc (17.30 ± 3.47 vs 13.38 ± 1.65; p < 0.182). CONCLUSIONS: Twelve months after LASIK, IOP measured with CT strongly correlated with GAT before surgery and could therefore provide an alternative method for measuring IOP after this surgery. More studies regarding this new convex prism are needed to assess its accuracy.

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.

30†A new step on amniotic membrane extract eye drops (AMEED) development for the treatment of severe ocular surface pathologies.

INTRODUCTION: Our tissue establishment developed a protocol for processing amniotic membranes as extracts to be re-hydrated and administered topically as eye drops, becoming a new approach to treat severe ocular surface pathologies. From 2015 to 2017 the safety and efficacy of the amniotic membrane extract eye drops (AMEED) were assessed in patients with severe ocular surface pathologies through clinical follow-up of ocular surface symptoms before and after regular application of the extract.Between 2018 and 2019 a study of 36 patients (50 eyes) treated with topical AMEED was conducted comparing 2 groups of patients: Dry Eye Disease (DED) and Wound Healing Delay (WHD) showing global similar symptomatic improvement in both groups (DED 88.9% vs WHD 100%; p= 0.486) with the WHD group especially consisting in general relief (78%) and DED group reporting more pain improvement (44%) (p=0.011). Regarding patients with autologous serum as 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. From January 2020 to November 2021 a growth stage has been observed including more patients while optimizing and scaling the process from donation to clinical use. MATERIALS AND METHODS: We record data of placenta donation and preparation of AMEED vials from 1/1/2020 to 30/11/2021 and its clinical use including the indications for treatment, number of requesting ophthalmologists and number of patients. RESULTS: In the study period a total of 378 placentas were processed to obtain AMEDD (61 in 2020 and 317 in 2021). The number of suitable vials obtained were: 1845 and 6464 respectively and 1946 vials are stored in quarantine pending release for clinical use.A total of 9365 vials were sent for treatment of ocular surface pathologies to 31 hospitals (98% in Catalonia) and 69 requesting ophthalmologists.The total number of patients treated was 204 and the indications for treatment were 82% DED and 18% WHD. CONCLUSION: After the new product development and introduction stages, a significant increase in the use of AMEED in Catalan hospitals was observed in 2020-2021. Follow-up data of these patients should be assessed to demonstrate its efficacy and achieve the maturity stage.

38†Lyophilized amniotic membrane for pterygium surgery: long-term outcomes.

PURPOSE: To investigate the tolerability, security and long-term efficacy of lyophilized amniotic membrane (LAM) as an alternative to cryopreserved amniotic membrane in pterygium surgery. MATERIAL AND METHODS: Prospective case series of patients with primary nasal pterygium who undergone pterygium surgery and LAM implant either with sutures or glue. Postoperative follow-up was until month 24. Clinical and cosmetic outcomes, quality of life (as ocular comfort), and complications were evaluated. RESULTS: LAM was stiff and easy to manipulate as well as no tearing occurred during surgery or suturing. 4 patients (3 males) had pterygium surgery and LAM implant two with sutures and the other two with glue. Ocular comfort was checked and similar among those patients with LAM glued or sutured. After 24 months, there were no issues about tolerability or adverse events. Lower cosmetic outcomes (recurrence) were stated in 3 patients. CONCLUSION: Our study showed that LAM could be an effective alternative to cryopreserved amniotic membrane for graft after pterygium excision surgery. Its main advantage, storage at room temperature, can make it of immediate availability. Further studies comparing clinical outcomes of pterygium surgery with cryopreserved amniotic membrane versus LAM would confirm the benefits of the last.

4†New strategies in the barcelona eye bank to minimize the impact of the COVID-19 pandemic.

Since the start of the pandemic, the tissue donation in Catalonia (Spain) has decreased drastically. At the beginning of the lockdown (from March to May 2020) there was a drop of around 70% in donation of corneas and of approximately 90% in donation of placentas. Despite the fast updating of standard operating procedures, we had big difficulties in different points. For instance, in the availability of the transplant coordinator for the donor detection and evaluation, in obtaining the necessary PPE (personal protective equipment), or in the resources available in the quality control laboratories for screening. This, added to the collapse that hospitals suffered due to the large number of patients hospitalized each day, made donation levels slowly rebound.In order to provide solutions to all patients, we tried to adapt quickly to these emerging changes.In the case of corneas, we found a scenario that we had never had before. Although the cornea transplant plummeted at the beginning of the confinement (decreased by 60% compared to 2019), we run out of corneas -even for emergency situations- at the end of March.This situation led us to develop a new type of therapeutic solution in our Eye Bank. The cryopreserved cornea for tectonic purposes is a tissue that is kept frozen at -196°C and can be preserved for up to 5 years. Therefore, it is a tissue that allows us to respond to possible emergencies in subsequent similar situations.Regarding amniotic membrane for ocular care indications, the strategy was completely different. For this kind of tissue, we carried out an adaptation of our processing with two different purposes. On the one hand, to make sure that we could inactivate the SARS-CoV-2 virus, if it was there. On the other hand, to increase the donation of placentas. For this, changes in the transport medium and in the antibiotic cocktail were performed. In addition, an irradiation step was added to the final product.Little by little, it seems that the donations of corneas and placentas have been recovering. However, it is necessary to think about future contingency strategies in case a stop in donation is repeated.

Vascular endothelial growth factor inhibitors for predominantly Caucasian myopic choroidal neovascularization: 2-year treatment outcomes in clinical practice: data from the Fight Retinal Blindness! Registry.

PURPOSE: To report the 24-month outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in predominantly Caucasian eyes in routine clinical practice. METHODS: Retrospective analysis of treatment-naïve eyes starting intravitreal injection of VEGF inhibitors of either bevacizumab (1.25 mg) or ranibizumab (0.5 mg) for mCNV from 1 January 2006 to 31 May 2018 that were tracked in the Fight Retinal Blindness! registry. RESULTS: We identified 203 eyes (bevacizumab-85 and ranibizumab-118) of 189 patients. The estimated mean (95% CI) change in VA over 24 months for all eyes using longitudinal models was +8 (5, 11) letters with a median (Q1, Q3) of 3 (2, 5) injections given mostly during the first year. The estimated mean change in VA at 24 months was similar between bevacizumab and ranibizumab [+9 (5, 13) letters for bevacizumab versus +9 (6, 13) letters for ranibizumab; p = 0.37]. Both agents were also similar in the mCNV activity outcomes, treatment frequency and visit frequency. CONCLUSIONS: The 24-month treatment outcomes of VEGF inhibitors for mCNV were favourable in this largest series yet reported of predominantly Caucasian eyes in routine clinical practice, with approximately two lines of visual gain and a median of three injections given mostly during the first year. These outcomes are similar to those reported for predominantly Asian eyes. Bevacizumab appeared to be as safe and effective as ranibizumab.

Twelve-month outcomes of ranibizumab versus aflibercept for macular oedema in branch retinal vein occlusion: data from the FRB! registry.

BACKGROUND/AIMS: To compare the efficacy of ranibizumab (0.5 mg) with aflibercept (2 mg) in the treatment of cystoid macular oedema due to branch retinal vein occlusion (BRVO) over 12 months. METHODS: A multicentre, international, database observational study recruited 322 eyes initiating therapy in real-world practice over 5 years. The main outcome measure was mean change in EDTRS letter scores of visual acuity (VA). Secondary outcomes included anatomic outcomes, percentage of eyes with VA >6/12 (70 letters), number of injections and visits, time to first inactivity, switching or non-completion. RESULTS: Generalised mixed effect models demonstrated that mean (95% CI) adjusted 12-month VA changes for ranibizumab and aflibercept were similar (+10.8 (8.2 to 13.4) vs +10.9 (8.3 to 13.5) letters, respectively, p=0.59). The mean adjusted change in central subfield thickness (CST) was greater for aflibercept than ranibizumab (-170 (-153 to -187) µm vs -147 (-130 to -164) µm, respectively, p=0.001). The overall median (Q1, Q3) of 7 (4, 8) injections and 9 (7, 11) visits was similar between treatment groups. First grading of inactivity occurred sooner with aflibercept (p=0.01). Switching was more common from ranibizumab (37 eyes, 23%) than from aflibercept (17 eyes, 11%; p=0.002). CONCLUSION: Visual outcomes at 12 months in this direct comparison of ranibizumab and aflibercept for BRVO in real-world practice were generally good and similar for the 2 drugs, despite a greater effect of aflibercept on CST and time to first grading of inactivity.

Trends in Corneal Transplantation in a Tertiary Hospital in Brazil.

PURPOSE: The purpose of this study was to analyze the evolving trends of surgical techniques and indications of corneal transplantation (CT) at a tertiary hospital in Brazil. METHODS: The medical records of all patients who underwent CT at the Hospital Oftalmológico de Sorocaba (Sorocaba Eye Hospital) from the Banco de Olhos de Sorocaba (Sorocaba Eye Bank) group in Sorocaba, Brazil, from January 1, 2012, to December 31, 2019, were analyzed. Data regarding age, sex, transplant indication, and surgical technique were collected. RESULTS: A total of 16,250 CTs were performed. There was a statistically significant decreasing trend of keratoconus-related CT ( P < 0.0001), with rates dropping from 41.7% among all CTs in 2012 to 25.5% in 2019. Penetrating keratoplasty, anterior lamellar keratoplasty, and endothelial keratoplasty (EK) accounted for 59.3%, 27.1%, and 7.8% of the CTs performed in 2012 and 33.3%, 16.4%, and 39.9% in 2019, respectively. A statistically significant decreasing trend was observed for penetrating keratoplasty ( P < 0.0001) and anterior lamellar keratoplasty ( P < 0.0001), whereas EK showed a statistically significant increasing trend during the period ( P < 0.0001). Among EKs, Descemet membrane EK increased statistically significantly from 12.8% in 2012 to 74.4% in 2019 ( P < 0.0001). CONCLUSIONS: This study shows relevant evolving trends in indications and preferred CT techniques in a tertiary hospital in Brazil.

Clinical features and management of presumed ocular tuberculosis: A long-term follow-up cohort study in a tertiary referral center in Brazil.

PURPOSE: To evaluate the clinical features and management of presumed ocular tuberculosis (OTB). METHOD: A prospective 3-year follow-up study of patients with ocular inflammation that performed Interferon-gamma release assay (IGRA) and tuberculin skin test (TST) was conducted in a tertiary referral center in Brazil. Patients with clinical signs highly suspect of OTB with a positive TST and/or IGRA with other causes ruled out were prescribed anti-tuberculosis therapy (ATT) during 9 months. Clinical features and treatment outcomes were recorded. RESULTS: Seventy-two patients (mean age 48.3 ± 15.7 years) were included in the study, and most were female (65.3%, n = 47). Posterior uveitis (43.1%, n = 31) was the main clinical feature. Multifocal choroiditis (25%, n = 18) was the most common choroidal involvement. Concomitant oral prednisone (45.8%, n = 33) during ATT was associated with more recurrences (p = 0.04). A significant difference (p < 0.001) between initial and final best-corrected visual acuity after ATT conclusion was observed. Cure or remission was observed in 58 (85.3%) patients that completed follow-up (n = 68). CONCLUSION: In our cohort some variation in demographics and ocular phenotypes of presumed OTB was observed. The high rates of cure or remission of our patients strongly support the ATT in presumed OTB. Oral corticosteroids during ATT were associated with higher recurrences rates.

Lyophilized amniotic membrane graft for primary pterygium surgery: preliminary results.

The aim of this study was to investigate the tolerability, safety and efficacy of new lyophilized amniotic membrane (LAM) presentation for ocular use. A prospective case-series cohort of four patients with primary nasal pterygium which undergone excision and LAM implantation was evaluated for complications and clinical outcomes. Surgical manipulation of LAM was also assessed. LAM was stiff and easy to manipulate as well as no tearing occurred during surgery or suturing. Ocular comfort was checked and similar among those patients with LAM glued or sutured. After 12 months, there were no issues about tolerability or adverse events. Lower cosmetic outcomes (recurrence) were stated in 3 patients. Our study showed that LAM could be an effective alternative to cryopreserved amniotic membrane for graft after pterygium excision surgery. Its main advantage, storage at room temperature, can make it of immediate availability. Further studies comparing clinical outcomes of pterygium surgery with cryopreserved amniotic membrane versus LAM would confirm the benefits of the last.

"Off-the-Shelf" Nerve Matrix Preservation.

Background: Decellularized human nerves overcome the limitations of the current treatments for large peripheral nerve injuries. However, the use of decellularized nerves requires an "off-the-shelf" availability for useful and actual clinical application. In this study, we addressed the preservation of the native and decellularized human nerve matrix in an integrative approach for tissue scaffold production. Materials and Methods: For native nerve matrix preservation analysis, we used histological examination and immunofluorescence to examine the structure, biomechanical assays to evaluate the tensile strength and Young's modulus, and analyzed the extracellular matrix (ECM) composition using enzyme-linked immunosorbent assay (ELISA) and biochemical assays for laminin, collagen and sulfated glycosaminoglycans (sGAG). After decellularization, nuclear remnants and DNA content were evaluated using 4',6-diamidino-2-phenylindole (DAPI) staining and the picogreen quantification assay, as well as immunofluorescence or ELISA for cell rests (S100 protein and myelin staining) evaluation. Decellularized cryopreserved scaffolds were assayed for biomechanics, ECM composition, and structural maintenance. Cytotoxicity assays were performed to evaluate the biocompatibility of the nerve matrix extracts after cryopreservation. Results: We compared different strategies for native nerve storage and found that preservation up to 7 days at 4°C in Roswell Park Memorial Institute medium maintained biomechanical properties, such as Young's modulus and tensile strength, along with the structure and ECM composition, regarding laminin, collagen, and sGAG. After a successful decellularization process, that eliminated cell remnants, nerve scaffolds were frozen in an "in house" formulated cryoprotectant, using an automatic controlled rate freezer. Nerve structure, ECM composition, and biomechanical properties were maintained before and after the freezing process in comparison with native nerves. The extracts of the nerve scaffolds after thawing were not cytotoxic and the freezing process sustained good viability in 3T3 cells (graphical abstract). Conclusion: Since our approach facilitates transport, storage, and provide a ready-to-use alternative, it could be used in a clinical application for the treatment of long-gap peripheral nerve injuries in regenerative medicine.

Amniotic membrane extract eye drops: a new approach to severe ocular surface pathologies.

A protocol for processing amniotic membrane as an extract to be re-hydrated and administered topically as eye drops (amniotic membrane extract eye drops, AMEED) has been developed. Safety and efficacy of AMEED was assessed in patients with severe ocular surface pathologies. prospective clinical follow-up of ocular surface symptoms before and after regular application of the AMEED for at least 4 weeks on patients with severe ocular surface disorders as chronic dry eye disease, limbal stem cell deficiency, neurotrophic ulcer and permanent and disabling symptomatology that were refractory to conventional treatment. Efficacy and tolerability were assessed based on patient-reported symptoms, objective measurements, and reports of adverse events. Thirty-six eyes from 25 patients were included. Although the visual quality function score, by means of a VQF25 questionnaire, was not statistically different after the treatment (p = 0.4657), there was a clear trend, statistically significant, towards the improvement in ocular symptoms like foreign body sensation, itching and stinging (p < 0.05) and clinical presentation of the pathology. All patients with corneal ulcer showed complete epithelization. Topically applied AMEED proved to be safe, well tolerated and effective in reducing the symptoms and clinical signs of severe ocular disease. Further studies are needed to confirm the best indications for AMEED use.