A minimum specification dataset for liquid ocular endotamponades: recommendations by a European expert panel.

PURPOSE: To propose a minimum specification dataset to characterize liquid ocular endotamponades (OEs), namely silicone oil (SO), heavy SO (HSO), perfluorodecalin (PFD), and perfluoro-octane (PFO), in terms of physicochemical properties, purity and available evidence of safety, in line with ISO16672:2020. METHODS: An evidence-based consensus using the expert panel technique was conducted. Two facilitators led a committee of 11 European experts. Facilitators prepared a dataset for each compound including the list of specifications relevant for the safety, identified by the group members on the basis of expertise and a comprehensive literature review. Each item was ranked by each member using a 9-point scale from 1 "absolutely to not include" to 9 "absolutely to include" in two rounds followed by discussion. Only items reaching consensus (score ≥ 7 from ≥ 75% of members) were included in the final datasets. RESULTS: For all OEs, consensus was reached to include manufacturer, density, refractive index, chemical composition, dynamic viscosity, interfacial and surface tension, endotoxins, in vitro cytotoxicity assessment, and any evidence from ex vivo and/or in vivo tests for safety assessment. Additional specifications were added for SO (molecular weight distribution, content of oligosiloxanes with MW ≤ 1000 g/mol, spectral transmittance) and PFD/PFO (% of pure PFD/PFO in the final product, vapor pressure, chemical analyses performed for safety assessment). CONCLUSION: The proposed evidence-based minimum specification datasets for SO, HSO, PFD, and PFO have the potential to provide surgeons and health service purchasers with an easily available overview of the most relevant information for the safety assessment of OEs.

Pachychoroid pigment epitheliopathy in keratoconic eyes.

PURPOSE: To report the association between keratoconus (KC) and pachychoroid pigment epitheliopathy (PPE). As secondary outcome, we explored the relation between subfoveal choroidal thickness (SFCT) and topometric indexes. METHODS: Retrospective, observational, cross-sectional, case-control study. Multicentric study including patients with KC and healthy controls. Each subject underwent a complete ophthalmological visit, Placido-based corneal topography, Scheimpflug corneal tomography and spectral-domain OCT (SD-OCT) with the enhanced depth imaging (EDI) mode on. Linear mixed models (LMM) were employed for comparison between groups, and to examine the impact of different topometric factors on SFCT. KC stages were defined according to Belin grading. RESULTS: Overall, 56 eyes from 35 KC patients and 52 eyes from 27 healthy, age- and axial length-matched control subjects were included in the study. PPE was found in 10 (17.9%) eyes from 8 KC patients, whereas was absent in all healthy controls. SFCT was statistically significantly higher in keratoconic eyes (median: 390 µm; interquartile range (IQR): 339 - 425 µm) compared to healthy eyes (median: 240 µm; IQR: 200 - 288 µm) (p < 0.001). SFCT did not differ across different KC stages and between keratoconic eyes with and without PPE. CONCLUSIONS: PPE is a relatively frequent finding in eyes with KC, being present in about 1 out of 6 cases, regardless of disease stage. KEY MESSAGES: What is known: Keratoconus (KC) is a corneal disorder commonly associated with other chorioretinal abnormalities. It is well known that keratoconic eyes display increased choroidal thickness, and the rare association between KC and central serous chorioretinopathy (CSC) has already been reported in the literature. WHAT IS NEW: We identified an association between KC and pachychoroid pigment epitheliopathy (PPE), a precursor or forme fruste of pachychoroid diseases, such as CSC. PPE presence is independent from corneal parameters and is observed in about 1 out 6 KC eyes.

The effect of optical degradation from cataract using a new Deep Learning optical coherence tomography segmentation algorithm.

PURPOSE: To assess the validity of the results of a freely available online Deep Learning segmentation tool and its sensitivity to noise introduced by cataract. METHODS: The OCT images were collected with a Spectralis SD-OCT (Heidelberg Engineering, Heidelberg, Germany) as part of normal clinical practice. Data were segmented using a freely available online tool called Relayer ( https://www.relayer.online/ ), based on a cross-platform Deep Learning segmentation architecture specifically adapted for retinal OCT images. The segmentations were read into MATLAB (The MathWorks, Natick, MA, USA) and analyzed. RESULTS: There was an excellent agreement between the ETDRS measurements obtained from the two algorithms. Upon visual inspection, the segmentation based on Deep Learning obtained with Relayer appeared more accurate except in one case of apparent good quality image showing interrupted segmentations in some of the B-scans. CONCLUSION: A freely available online Deep Learning segmentation tool showed good and promising performance in healthy retinas before and after cataract surgery, proving robust to optical degradation of the image from media opacities.

Development and preliminary evaluation of a novel preoperative index for quantitative analysis of photoreceptor loss in full-thickness macular holes.

PURPOSE: To identify novel quantitative parameters for evaluating photoreceptor loss in full-thickness macular holes (FTMH), exploring their potential clinical impact on postoperative functional and anatomical recovery. METHODS: This pilot study enrolled 38 eyes from 38 patients diagnosed with FTMH. Preoperatively, eyes underwent analysis and were subsequently followed for six months post-surgery. Best-corrected visual acuity (BCVA) was recorded, and cross-sectional images of FTMH were obtained using B-scan optical coherence tomography (OCT) and en-face OCT. Quantitative assessment of ellipsoid zone (EZ) and external limiting membrane (ELM) integrity changes was conducted and correlated with postoperative anatomical and functional recovery. The photoreceptor Integrity Index (PIIN), calculated as the ratio of photoreceptor area to lumen hole area measured at customized segmentation, was correlated with the minimum and base diameters of the hole, positive change in BCVA, preoperative EZ defect (EZd), preoperative ELM defect (ELMd), and changes in EZ and ELM over the six-month follow-up period (∆-EZ and ∆-ELM). The main outcome measures focused on evaluating the effectiveness of PIIN in predicting postoperative anatomical and functional changes. RESULTS: A higher PIIN correlated with a greater BCVA change over six months (p < 0.001). Univariate regression analysis using the PIIN as a predictor for positive change in BCVA (|∆-BCVA| [logMAR]) over time yielded significant results (p < 0.001). Additionally, the PIIN significantly correlated with EZd at baseline, ELM at baseline, and ELMd change over the six-month follow-up period. CONCLUSION: The PIIN shows promise as a tool for evaluating photoreceptor loss in macular holes and estimating postoperative functional and anatomical recovery. KEY MESSAGES: What is known Previous studies have extensively used optical coherence tomography (OCT) to investigate various biomarkers for assessing patients with full-thickness macular hole (FTMH), without considering detailed MH ultrastructural features Existing indexes used to predict surgical outcomes for FTMH primarily depend on geometrical parameters and do not integrate detailed ultrastructural characteristics, such as cellular components.  What is new A novel concept introduces the quantitative measurement of residual photoreceptors located at the edge of FTMH. The Photoreceptor Integrity Index (PIIN) integrates different ultrastructural components of macular holes, aiming to become a valuable clinical tool to predict both anatomical and functional recovery outcomes following surgical intervention for FTMH.

Temperature control during pars plana vitrectomy.

PURPOSE: To evaluate the impact of temperature-controlled pars plana vitrectomy (PPV) on structural and functional outcomes in a rabbit eye model in vivo. METHODS: Ten healthy New Zealand White rabbits underwent temperature-controlled PPV in the right eye (group A), using a device specifically designed to heat the infusion fluid/air and integrated into the vitrectomy machine, and conventional PPV in the left eye (group B). Both eyes received ophthalmic examination and electroretinography (ERG) before and 1 week postoperatively. After 1-week ERG, rabbits were enucleated and then sacrificed. Histological and immunohistochemical examinations were performed on enucleated eyes and expression of glial fibrillary acidic protein (GFAP) and vimentin investigated. RESULTS: Postoperatively, only group B showed significantly decreased amplitude and increased latency of a-wave at 3 cd·s/m2 (p = 0.001 and 0.005, respectively). Significant increase of b-wave latency at 0.01 cd·s/m2 was detected in both groups (p = 0.019 and 0.023, respectively). Postoperatively, amplitude of oscillatory potentials (OPs) increased significantly in group A (p = 0.023) and decreased in group B. In both groups, OPs latency significantly increased at 1-week test (P < 0.05). A greater number of eyes without structural retinal alterations was detected in group A compared to group B (6 vs 5, respectively). GFAP expression was higher in group B than group A, even if the difference was not statistically significant. CONCLUSION: Temperature-controlled PPV resulted in more favorable functional and structural outcomes in rabbit eyes compared with conventional PPV, supporting the potential beneficial role of the intraoperative management of intraocular temperature in vitreoretinal surgery.

TANGENTIAL RETINAL DISPLACEMENT INCREASES AFTER MACULAR PUCKER SURGERY: An Apparent Nonsense.

PURPOSE: To measure the tangential retinal displacement and vision before and after macular pucker surgery and study if pars plana vitrectomy with epiretinal membrane peeling allows the reconstitution of previous anatomy or else it results in a different configuration. METHODS: Retrospective series of patients undergoing pars plana vitrectomy for epiretinal membrane, with >6-month follow-up before and after surgery, complete with best-corrected visual acuity, optical coherence tomography, M-Charts, and infrared retinography. Tangential retinal displacement between earliest visit (T E ), time of surgery (T 0 ), and latest available visit (T L ) of the examined retina, concentric circles at 0.5, 1.5, and 4.5 mm radii, and the central horizontal and vertical meridians were measured. Tangential displacement was calculated as the optical flow of consecutive infrared photographs. RESULTS: The study comprised 32 patients: 15 men and 17 women. Average preoperative and postoperative follow-up were 23.4 ± 27.9 months and 19.2 ± 11.8 months, respectively. Best-corrected visual acuity reduced before surgery (0.69 ± 0.16 Snellen to 0.46 ± 0.17; P < 0.001) and increased after (0.866 ± 0.16 Snellen; P < 0.001). Horizontal and vertical metamorphopsia increased between before surgery but only horizontal metamorphopsia significantly reduced after. Average tangential displacement before surgery was 35.6 ± 29.9 µ m versus 56.6 ± 41.3 µ m after ( P = 0.023). Preoperative and postoperative displacement within the fovea was less than over the entire area ( P < 0.001). CONCLUSION: Retinal tangential displacement between diagnosis and surgery (T E - T 0 ) is less than the displacement occurring after surgery (T 0 - T L ). Postoperative displacement does not represent the restoration of the anatomy existing before the disease ensued but rather the resulting equilibrium of newly deployed forces.

Optimizing surgical performance and safety in endoresection of uveal melanoma.

PURPOSE: To present a standardized surgical technique for endoresection of uveal melanoma (UM) minimizing the risk of serious adverse events, including fatal gas embolism. METHODS: Ten UM patients underwent endoresection following proton beam radiotherapy for radiotherapy-related vascular complications. Vortex veins located in correspondence of the tumor base had been cauterized at the time of tantalum markers placement. Endoresection was performed following complete 25G vitrectomy, endolaser and endodiathermy. The tumor was removed using a subretinal or transretinal approach depending on retinal infiltration. If needed, perfluorodecalin (PFD) was injected to stabilise the retina. Fluid-silicone oil (SO) or PFD-SO exchange was performed, avoiding air. RESULTS: Endoresection was successfully performed in all eyes with no intraoperative complications. Mean follow-up (FU) was 10.8 ± 3.2 months. One patient was enucleated due to neovascular glaucoma. At the last FU, the remaining patients had the eye preserved and no signs of local recurrence or neovascular glaucoma. CONCLUSION: Our standardized surgical technique for UM endoresection appeared to be safe, minimizing the risk of serious intraoperative and postoperative adverse events.

RETINAL TECTONICS AFTER MACULAR PUCKER SURGERY: Thickness Changes and En Face Displacement Recovery.

PURPOSE: To study visual function, retinal layer thickness changes, and tangential displacement after pars plana vitrectomy for epiretinal membrane. METHODS: Retrospective series of patients undergoing pars plana vitrectomy for epiretinal membrane, with 6-month follow-up including best-corrected visual acuity, optical coherence tomography, M-charts, epiretinal membrane grading, and infrared fundus photograph at time 0 (T0, preop) at months 1 (T1), 3 (T3), and 6 (T6) postop (±1 week). Retinal layer thickness and tangential ( en face ) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En face displacement was calculated as optical flow of consecutive images. RESULTS: Average best-corrected visual acuity improved from 0.28 ± 0.08 logarithm of Minimum Angle of Resolution at T0 to 0.16 ± 0.25 at T6 ( P = 0.05), best-corrected visual acuity improvement correlated with best corrected visual acuity (BCVA) at T0 ( P < 0.001). Vertical metamorphopsia decreased from 1.33° ± 0.70° at T0 to 0.82° ± 0.69° at T6 ( P < 0.05). Foveal thickness reduced from 453 ± 53 µ m at T0 to 359 ± 31 µ m at T6 ( P < 0.05) and reduction correlated with best-corrected visual acuity improvement ( P < 0.05). Foveal layers decreased ( P < 0.05) in all cases. The mean en face deformation was 155.82 ± 50.17 µ m and mostly occurred in the first month: T0-T1 displacement was 83.59 ± 30.28 µ m, T1-T3 was 36.28 ± 14.45 µ m, while T3-T6 was 39.11 ± 22.79 µ m ( P < 0.001) on average. Perifoveal and parafoveal deformation correlated with optical coherence tomography foveal thickness reduction at all time intervals (1, 3, and 6 months: P < 0.01). CONCLUSION: Epiretinal membrane peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en face and in-depth changes correlate with visual function.

THREE-DIMENSIONAL RETINAL DISPLACEMENT BEFORE AND AFTER MACULAR PUCKER SURGERY.

PURPOSE: To measure the coronal and sagittal retinal displacement before and after surgery for epiretinal membranes in InfraRed horizontal foveal sections and optical coherence tomography scans and describe displacement tridimensionality, vision loss, and metamorphopsia. METHODS: Retrospective series with greater than 6-month average follow-up before and after surgery. The record included best-corrected visual acuity, optical coherence tomography, M-charts, and InfraRed retinography. Overall, pre- and postoperative coronal and sagittal retinal displacement across the entire field, concentric circles at 0.5-, 1.5-, and 4.5-mm radii, and the central horizontal and vertical meridian were calculated as the optical flow of consecutive images. RESULTS: This study comprised 10 patients (4 men, 6 women), with 22.7 ± 25.2 months follow-up before surgery and 16.2 ± 7.3 months after. Best-corrected visual acuity reduced before surgery (0.15 ± 0.67 logarithm of minimum angle of resolution to 0.38 ± 0.85 logarithm of minimum angle of resolution; P < 0.05) and increased afterward (0.086 ± 0.61 logarithm of minimum angle of resolution; P = 0.003). Preoperative coronal displacement was 30.1 ± 29.1 µm versus 67.0 ± 23.4 µm after (P = 0.002). Sagittal retinal displacement was 140.9 ± 84.6 µm before surgery, 339.7 ± 172.5 µm after (P = 0.017), and 357.6 ± 320.8 µm across the entire follow-up. Preoperative best-corrected visual acuity decreases correlated with the foveal coronal displacement. Vertical metamorphopsia correlated with the average coronal displacement within a 4.5-mm radius. Pre- and postoperative sagittal displacement correlated with horizontal metamorphopsia (P = 0.006 and P = 0.026). Postoperative sagittal displacement correlated with postoperative best-corrected visual acuity (P = 0.026) and foveal thickness (P = 0.009). CONCLUSION: This study confirms that postoperative displacement is greater than preoperative and that sagittal displacement is greater than coronal and correlates with best-corrected visual acuity and metamorphopsia changes.

EN FACE OPTICAL COHERENCE TOMOGRAPHY MORPHOLOGY OF MACULAR PUCKER CORRELATES WITH METAMORPHOPSIA: Possible Role of the Henle Fiber Layer.

PURPOSE: To describe macular pucker contraction patterns with en face optical coherence tomography (OCT), to provide a correlation with metamorphopsia scores, and to discuss the protective role of the Henle fiber layer (HFL) against tangential traction. METHODS: Retrospective, institutional, observational, and consecutive case series. Clinical charts, M-charts scores, and structural and en face OCT imaging of patients diagnosed with macular pucker were reviewed. RESULTS: A 120 eyes of 114 consecutive patients diagnosed with macular pucker were included. En face OCT patterns of macular pucker contraction were foveal in 51 of 120 eyes (42.5%) and extrafoveal in 69 of 120 eyes (57.5%). Foveal macular puckers had regular, a concentric, circle morphology in the HFL (46/51 eyes, 90.2%), whereas extrafoveal membranes had irregular, distorted, circular HFL morphology (62/69 eyes, 89.8%; P < 0.001). Foveal contraction morphology and regular HFL pattern, as well as extrafoveal contraction morphology and an irregular HFL pattern, highly correlated one with another (P < 0.001 in both cases). Foveal macular puckers with regular HFL patterns had significantly less vertical and horizontal M-charts scores as compared with extrafoveal membranes with irregular HFL (P < 0.001 in both cases). Ellipsoid zone and external limiting membrane defects were rare in the parafoveal region (5/120 eyes, 4.2%). Visual acuity did not correlate with metamorphopsia scores (P = 0.903). CONCLUSION: En face OCT imaging identifies macular pucker contraction patterns that correlate with metamorphopsia scores and that can be used alongside the current structural OCT staging system to guide clinicians in the surgical decision-making process.

Endoscopic endonasal dacryocystorhinostomy: impact of long-standing disease on surgical outcomes.

PURPOSE: To assess whether the duration of disease may influence the surgical success of Endonasal Endoscopic DCR (EE-DCR) in patients affected by nasolacrimal duct obstruction (NLDO). METHODS: Single-center observational retrospective analysis on EE-DCR via posterior trans-ethmoidal approach. Consecutive patients were enrolled in 2021-2024 and evaluated with proper questionnaires; resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). Also, patients were asked to complete the Hospital Anxiety and Depression Scale (HADS) at each timepoint. The sample was divided based on the duration of disease (group A: ≤ 24 months, group B: > 24 months). RESULTS: Ninety-one patients were included. At baseline no differences were observed between the two groups. At both timepoints, Munk score was significantly lower in Group A compared to Group B, while a difference in dacryocystitis rate was observed only at T2. Anxiety scores differed significantly at T2, although no differences were observed for depression. At paired analysis, all groups improved significantly at T1 compared to baseline, whereas no further improvement was observed between T2 and T1. A significantly higher improvement was observed in group A for the Munk and HADS-A scores over timepoints, whereas there was no significance for dacryocystitis rate and HADS-D. Also, group A showed a higher complete success rate compared to group B (p = 0.041). Finally, linear regression confirmed a positive relationship between Munk and anxiety scores and the duration of disease at T2. CONCLUSIONS: Our findings showed that long-lasting NLDO symptoms may be associated with worse EE-DCR surgical outcomes.

Differential diagnosis of myopic choroidal neovascularization (mCNV): insights from multimodal imaging and treatment implications.

PURPOSE: The aim of this article is to conduct a comprehensive systematic review about the current understandings and differential diagnosis of myopic choroidal neovascularization (mCNV) and other several similar diseases, describing their multimodal imaging analysis, prognostic implications, and current types of management. METHODS: This systematic review was performed based on a search on the PubMed database of relevant papers regarding mCNV and other entities discussed in the paper, according to our current knowledge. RESULTS: Through the integration of a multimodal imaging approach, especially optical coherence tomography (OCT), along with accurate demographic and clinical assessment, it becomes possible to effectively differentiate mCNV from similar yet heterogeneous entities. These conditions include macular hemorrhage due to new lacquer crack (LC) formation, inflammatory diseases such as punctate inner choroidopathy (PIC)/multifocal choroidits (MFC) and epiphenomenon multiple evanescent white dot syndrome (Epi-MEWDS), neovascular age-related macular degeneration (nAMD), idiopathic CNV (ICNV), dome-shaped macula (DSM) with subretinal fluid, retinal pigment epithelium (RPE) humps, angioid streaks (AS), choroidal rupture (CR), and choroidal osteoma (CO). Each one of these entities will be described and discussed in this article. CONCLUSION: Myopic choroidal neovascularization is a common retinal condition, especially among young individuals. Accurate diagnosis and differentiation from similar conditions are crucial for effective treatment. Multimodal imaging, particularly OCT, plays a crucial role in precise assessment. Future research should focus on defining biomarkers and distinguishing features to facilitate prompt treatment.

INTRAOCULAR EMULSION OF SILICONE OIL (ITEMS) GRADING SYSTEM: An Evidence-Based Expert-Led Consensus.

PURPOSE: To propose the InTraocular EMulsion of Silicone oil (ITEMS) grading system for the assessment of silicone oil (SiO) emulsion, applicable in a routine clinical setting and validated through an expert-led consensus procedure. METHODS: Seven experts on intraocular liquid tamponades, led by a facilitator, performed a literature review on the detection of SiO emulsion. Based on the proposed ideas, a questionnaire was developed and submitted to the experts on the methods to detect SiO emulsion and the items to grade. After 2 rounds of individual ranking using a 9-point scale and related discussion, the final grading system was developed including items that reached consensus (score ≥7 from ≥75% of members). RESULTS: The agreed ITEMS grading system includes the identification of SiO microbubbles and large SiO bubbles through slit-lamp biomicroscopy, gonioscopy, fundus examination under mydriasis, or ultra-wide-field fundus photography. Moreover, macular and disk optical coherence tomography are used to detect SiO-associated hyperreflective dots. CONCLUSION: An evidence-based expert-led consensus was conducted to develop grading system of SiO emulsion, allowing, for the first time, homogenous collection of data on SiO emulsion. This has the potential to improve the understanding of the role and clinical relevance of SiO emulsion, allowing comparisons between different studies.

The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications.

Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.

How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization.

Inherited macular dystrophies refer to a group of degenerative conditions that predominantly affect the macula in the spectrum of inherited retinal dystrophies. Recent trends indicate a clear need for genetic assessment services in tertiary referral hospitals. However, establishing such a service can be a complex task due to the diverse skills required and multiple professionals involved. This review aims to provide comprehensive guidelines to enhance the genetic characterization of patients and improve counselling efficacy by combining updated literature with our own experiences. Through this review, we hope to contribute to the establishment of state-of-the-art genetic counselling services for inherited macular dystrophies.

A retrospective, multicenter study on the management of macular holes without residual internal limiting membrane: the refractory macular hole (ReMaHo) study.

PURPOSE: To evaluate the surgical management, outcomes and prognostic factors of full thickness macular holes without residual internal limiting membrane (NO-ILM FTMHs). METHODS: We performed a multicenter, retrospective study of 116 NO-ILM FTMHs. Human amniotic membrane (hAM) plug, autologous ILM free flap transplantation (AILMT), and autologous retinal graft transplantation (ART) were performed in 58, 48, and 10 patients, respectively. Data were collected before and up to 12 months after surgery. The primary outcomes were hole closure and final best-corrected visual acuity (BCVA). RESULTS: The final BCVA (0.78 ± 0.51 logMAR) was significantly better than and correlated with the initial BCVA (p < 0.0001 and p = 0.004, respectively). Hole closure was achieved in 92% of eyes. The minimum FTMH diameter was wider and final BCVA was lower in the ART group than in the other groups (p < 0.003 and p < 0.001, respectively). FTMHs with diameter > 680 µm had a higher closure rate with hAM than with AILMT (p = 0.02). CONCLUSIONS: AILMT and hAM were the most frequently performed surgeries with both high closure rate and significant functional improvement. Preoperative BCVA was correlated with final BCVA. The minimum FTMH diameter may guide the treatment choice.

Where Are We with RPE Replacement Therapy? A Translational Review from the Ophthalmologist Perspective.

The retinal pigmented epithelium (RPE) plays a pivotal role in retinal homeostasis. It is therefore an interesting target to fill the unmet medical need of different retinal diseases, including age-related macular degeneration and Stargardt disease. RPE replacement therapy may use different cellular sources: induced pluripotent stem cells or embryonic stem cells. Cells can be transferred as suspension on a patch with different surgical approaches. Results are promising although based on very limited samples. In this review, we summarize the current progress of RPE replacement and provide a comparative assessment of different published approaches which may become standard of care in the future.

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential.

Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.

Curcumin in Retinal Diseases: A Comprehensive Review from Bench to Bedside.

Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.

Ex vivo evaluation of retinal cytotoxicity after the use of multiple medical devices in pars plana vitrectomy in porcine eyes.

This study aimed to evaluate viability of retinal cells after the use of multiple intraoperative devices, namely a vitreal dye (triamcinolone acetonide,TA), a ERM/ILM dye (solution of trypan blue 0.15% and brilliant blue 0.025%), and two intraocular tamponades, namely perfluoro-n-octane, (PFO) and silicone oil (SO 1000 cSt), with minimal and maximal removal of their residues, during a simulated pars plana vitrectomy (PPV) in porcine eyes ex-vivo. The in vitro cytotoxicity of each of these compounds was verified on ARPE-19 cells by direct tests according to the ISO 10993-5 (2009). Pars plana vitrectomy was performed on 25 enucleated porcine eyes divided in five groups according to the following conditions: Group A) No surgery control: eye bulbs were kept at room temperature for 40 min; Group B) Sham surgery: PPV with the sole use of BSS for 40 min; Group C) Cytotoxic control: PPV with BSS infusion (20 min) followed by intravitreal injection of 1H-PFO (contact time: 20 min); Group D) Surgery with residues: PPV with BSS infusion and sequential intravitreal injection of TA, ERM/ILM dye, PFO and SO, with minimal removal of each compound after a specified contact-time (overall duration: 40 min); Group E) Surgery with minimal residues: PPV performed as in group D, but with maximal removal of each compound (overall duration: 40 min). All the experimental procedures were performed at room temperature. Immediately after surgery, the retina was extracted from each eye bulb and samples of 3-mm diameter were prepared. Retinal viability was determined for each sample by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. A cell viability <70% was considered the cytotoxicity threshold. Kruskal-Wallis test was used to evaluate the differences in retinal viability between groups. No cytotoxicity was detected in retinal samples in groups A, B and E. Samples from eye bulbs that had undergone surgery with minimal removal of residues (group D) and cytotoxic controls (group C) showed high retinal cytotoxicity. The tested conditions indicated that the combined use of TA, ERM/ILM dye, PFO and SO during PPV does not affect retinal cells viability if all the devices are properly removed, whereas the cytotoxicity detected in group D may suggest that the presence and accumulation of the residues of the compounds used intraoperatively could negatively impact retinal viability due to a cumulative and/or synergistic cytotoxic effect between them, supporting the crucial role of an optimal removal of the intraoperative medical devices to ensure a safe vitrectomy to the patient.