Glaucoma Treatment and Hydrogel: Current Insights and State of the Art

Aqueous gels formulated using hydrophilic polymers (hydrogels) and those based on stimuli-responsive polymers (in situ gelling or gel-forming systems) attract increasing interest in the treatment of several eye diseases. Their chemical structure enables them to incorporate various ophthalmic medications, achieving their optimal therapeutic doses and providing more clinically relevant time courses (weeks or months as opposed to hours and days), which will inevitably reduce dose frequency, thereby improving patient compliance and clinical outcomes. Due to its chronic course, the treatment of glaucoma may benefit from applying gel technologies as drug-delivering systems and as antifibrotic treatment during and after surgery. Therefore, our purpose is to review current applications of ophthalmic gelling systems with particular emphasis on glaucoma

Precision Medicine in Glaucoma: Artificial Intelligence, Biomarkers, Genetics and Redox State

Glaucoma is a multifactorial neurodegenerative illness requiring early diagnosis and strict monitoring of the disease progression. Current exams for diagnosis and prognosis are based on clinical examination, intraocular pressure (IOP) measurements, visual field tests, and optical coherence tomography (OCT). In this scenario, there is a critical unmet demand for glaucoma-related biomarkers to enhance clinical testing for early diagnosis and tracking of the disease’s development. The introduction of validated biomarkers would allow for prompt intervention in the clinic to help with prognosis prediction and treatment response monitoring. This review aims to report the latest acquisitions on biomarkers in glaucoma, from imaging analysis to genetics and metabolic markers

Microperimetric evaluation and predictive factors of visual recovery after successful inverted internal limiting membrane-flap technique for macular hole in high myopic eyes

IntroductionInverted Internal Limiting Membrane (ILM)-flap technique demonstrated its effectiveness, in terms of anatomical closure rate and visual acuity recovery for high myopic macular holes. We evaluated macular function after a successful inverted ILM-flap for macular holes in high myopic eyes (hMMH) using microperimetry to predict visual prognosis.MethodsA retrospective study on 23 eyes of 23 patients after surgical closure of hMMH, was performed. All patients underwent inverted ILM-flap and gas tamponade. Cataract surgery was performed in phakic eyes. Study outcomes including best-corrected visual acuity (BCVA), retinal sensitivity (RS) at central 12°, central retinal sensitivity (CRS) at central 4° and mean deviation (MD), and fixation behavior as bivariate contour ellipse area (BCEA, degrees2) measured by microperimetry, were evaluated over 6 months. A mixed-effects model was used to evaluate and compare the repeated measurements of outcomes between phakic and pseudophakic eyes. A regression model was performed to assess the relationship between BCVA at 6 months and independent variables.ResultsOverall mean BCVA improved from 0.98 ± 0.21 logMAR at baseline to 0.47 ± 0.31 logMAR at the last follow-up (p < 0.001). Over 6 months, overall sensitivity measurements improved (RS, p = 0.001; CRS, p < 0.0001; MD, p = 0.03), and the BCEA decreased in dimension, although not significantly (p ≥ 0.05). The mixed model revealed a significantly better effect of inverted ILM-flap combined with cataract surgery on BCVA and CRS in phakic eyes than inverted ILM-flap alone in pseudophakic ones. The regression model revealed a relationship of 6-month BCVA with pre-operative BCVA (β = 0.60, p = 0.02) and RS (β = −0.03, p = 0.01).ConclusionThe inverted ILM-flap technique significantly improved visual acuity and retinal sensitivity after the hMMH closure, particularly when combined with cataract extraction. Pre-operative visual acuity and retinal sensitivity at central 12° may predict post-surgical visual acuity

Clinical Outcome and Drug Expenses of Intravitreal Therapy for Diabetic Macular Edema: A Retrospective Study in Sardinia, Italy

Background: Diabetic macular edema (DME) is a leading cause of visual loss in working-age adults. The purpose of this retrospective study was to perform an epidemiological analysis on DME patients treated with intravitreal drugs in a tertiary hospital. The clinical outcome, adverse drug reactions (ADRs), and intravitreal drug expenses were assessed. Methods: All DME patients treated with Ranibizumab, Aflibercept, Dexamethasone implant, and Fluocinolone Acetonide implant at the Sassari University Hospital, Italy, between January 2017 and June 2020 were included. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were measured. ADRs and drug expenses were analyzed. Results: Two-hundred thirty-one DME patients (mean age: 65 years) received intravitreal agents. Mean CMT and BCVA were 380 μm and 0.5 LogMAR at baseline, 298 μm and 0.44 logMAR after one year (p = 0.04), and 295 μm and 0.4 logMAR at the end of the follow-up period. A total of 1501 intravitreal injections were given; no major ADRs were reported. Treatment cost was €915,000 (€261,429/year). Twenty non-responders to Ranibizumab or Aflibercept were switched to a Dexamethasone implant. In these patients, mean CMT and BCVA were 468 µm and 0.5 LogMar at the time of switching and 362 µm and 0.3 LogMar at the end of the follow-up (p = 0.00014 and p = 0.08, respectively). Conclusion: Results confirm that Ranibizumab, Aflibercept, and Dexamethasone implant are effective and safe in DME treatment. A switch to Dexamethasone implant for patients receiving Aflibercept or Ranibizumab with minimal/no clinical benefit should be considered

Effects of diabetic retinopathy on longitudinal morphological changes in AMD-associated type 1 macular neovascularization

Abstract The purpose of this study was to investigate the effect of diabetic retinopathy (DR) on longitudinal morphological changes in AMD-associated type 1 macular neovascularization using optical coherence tomography angiography (OCTA). We enrolled fifty treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV. Twenty of 50 eyes were affected by mild DR. En face OCT angiography were examined for the MNV lesion area (mm2), the MNV flow area (mm2), the central macular thickness (CMT) and the BCVA. The OCTA acquisition was performed at the following visits: (i) before the loading phase (LP) of intravitreal injection of aflibercept (T1), and (ii) 1 month after the last intravitreal injection of loading phase comprising 3 monthly injections (T2). All morpho-functional parameters showed a significantly change at T2 compared to T1 values in both groups. Furthermore, we found a greater MNV area reduction after LP in eyes without DR (P = 0.023). With regard to the remaining parameters, no significant changes were found between two groups (P > 0.05). Our analysis revealed a less MNV area reduction after loading dose of anti-VEGF therapy in eyes affected by diabetic retinopathy

How Reliable Is Pyramidal Wavefront-Based Sensor Aberrometry in Measuring the In Vivo Optical Behaviour of Multifocal IOLs?

Cataract or refractive lens surgery, along with the implantation of multifocal intraocular lenses (MF-IOL), enables a complete range of functional far, near and intermediate vision. Refractive, diffractive and extended depth of focus (EDoF) or combination of these principles represent the technology used to obtain this multifocality. Aberrometry makes it possible to study the aberrations induced by MF-IOLs. Among the different optical principles available to measure ocular aberrations, pyramidal wavefront-based sensor (PWS) aberrometry shows the highest resolution with MF-IOLs. Retinal image quality measured by a PWS aberrometer differed significantly according to the technology of the implanted lens. Monofocal and diffractive lenses showed the highest values of far-distance retinal image quality, followed by refractive and EDoF lenses; however, retinal image quality analysed in diffractive lenses appears to be more dependent on residual refractive error. Considering this limitation, PWS-aberrometry could be used to compare diffractive lenses. Nevertheless, further studies are needed to provide additional information about the clinical retinal image quality of MF-IOLs and to help surgeons in the important preoperative selection of IOLs

Short-Term Morphofunctional Changes in Previously Treated Neovascular AMD Eyes Switched to Brolucizumab

The purpose of the study is to explore the morphofunctional fluctuations in eyes treated for neovascular AMD (nAMD) when treatment is switched from aflibercept or ranibizumab to brolucizumab. A total of 31 eyes of 31 patients with nAMD with type 1 macular neovascularization (MNV) were included. All patients were imaged using spectral domain optical coherence tomography (SD-OCT). The OCT acquisition was performed at the following visits: (i) “T1 visit” corresponding to the last follow-up examination in which an intravitreal injection of aflibercept or ranibizumab was performed before switching to brolucizumab because of the lack of improvement and (ii) “T2 visit” corresponding to the examination performed 1 month after T1, the latter visit corresponding to the day when a switch to brolucizumab injection was performed, (iii) and 1 month after the latter injection “(T3)”. The main outcome measures were: (1) central macular thickness (CMT), (2) choroidal vascularity index (CVI), (3) subfoveal choroidal thickness (CT), and best-corrected visual acuity (BCVA). Functional outcome showed significant differences at each time. Mean ± SD BCVA was 0.43 ± 0.12 LogMAR at T1 and 0.56  ±  0.16 LogMAR at T2 (p = 0.038). A significant improvement in BCVA was displayed at T3 (0.34  ±  0.21 LogMAR) as compared with T2 (p  = 0.019). CMT analysis showed fluctuations three times. In detail, T2 displayed a thicker CMT in comparison with T1, although not statistically significant (p = 0.12). Contrariwise, T3 showed a thinner CMT in comparison with T2 (p = 0.002). Analyzing CVI among the three different times, the luminal choroidal area (LCA) and total choroidal area (TCA) showed significantly different values before and after switching to brolucizumab. T2 showed a significant reduction in both vessel lumen and total area compared with T1 (p = 0.032 and p  =  0.046, respectively). Moreover, T3 showed a greater value of both LCA and TCA in comparison with T2 (p = 0.008 and p  =  0.01, respectively). CT did not show significant differences at each time (p > 0.05). Our results reported early experiences on morphofunctional fluctuations in patients with nAMD who switched to brolucizumab. The anatomical impact of brolucizumab administration appears to result in choroidal vascular enlargement, accompanied by the resolution of subretinal fluid (SRF) and intraretinal fluid (IRF)

Combined Branch Retinal Artery and Central Retinal Vein Occlusion: A Systematic Review

We performed a systematic review and analyzed the current available data on branch retinal artery occlusion (BRAO) with simultaneous central retinal vein obstruction (CRVO), a rarely described occurrence. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Studies were considered eligible if they (1) described patients with simultaneous BRAO + CRVO and (2) had been published in peer-reviewed journals. We initially identified 239 records from databases. Ultimately, only 19 reports met the selection criteria. Twenty-nine patients (15 men, 14 women; mean age 43 ± 15 years) were analyzed. Seventeen (59%) patients presented vascular risk factors. Mean visual acuity at onset and final visual outcome were 20/83 and 20/45, respectively, an insignificant improvement. Vision improved in 48% of cases. A marked heterogeneity in treatment approach was found. Eight (28%) patients received no therapy, whereas for 21 (72%) a large variety of topical and/or systemic drugs was given. In the treated group, mean visual acuity at onset and final visual outcome were 20/90 and 20/44, respectively, a not statistically significant improvement. Results suggest that combined BRAO + CRVO occurs at a younger age than isolated BRAO or CRVO. At present, there is insufficient evidence to support any specific management to improve vision in simultaneous BRAO + CRVO

A Radiomic-Based Machine Learning System to Diagnose Age-Related Macular Degeneration from Ultra-Widefield Fundus Retinography

The present study was conducted to investigate the potential of radiomics to develop an explainable AI-based system to be applied to ultra-widefield fundus retinographies (UWF-FRTs) with the objective of predicting the presence of the early signs of Age-related Macular Degeneration (AMD) and stratifying subjects with low- versus high-risk of AMD. The ultimate aim was to provide clinicians with an automatic classifier and a signature of objective quantitative image biomarkers of AMD. The use of Machine Learning (ML) and radiomics was based on intensity and texture analysis in the macular region, detected by a Deep Learning (DL)-based macular detector. Two-hundred and twenty six UWF-FRTs were retrospectively collected from two centres and manually annotated to train and test the algorithms. Notably, the combination of the ML-based radiomics model and the DL-based macular detector reported 93% sensitivity and 74% specificity when applied to the data of the centre used for external testing, capturing explainable features associated with drusen or pigmentary abnormalities. In comparison to the human operator’s annotations, the system yielded a 0.79 Cohen κ, demonstrating substantial concordance. To our knowledge, these results are the first provided by a radiomic approach for AMD supporting the suitability of an explainable feature extraction method combined with ML for UWF-FRT