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Abstract Background The aim of this study was to compare functional and anatomical changes in patients with small full thickness macular holes (FTMHs) who underwent pars plana vitrectomy (PPV) with or without Internal limiting membrane (ILM) peeling. Methods 42 eyes of 42 patients diagnosed for FTMHs (

Abstract Background To report real-world outcomes of patients with primary Reghmatogenous Retinal Detachment (RRD) treated with Pneumatic Retinopexy (PnR) according to the indications of the Pneumatic Retinopexy versus Vitrectomy for management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) trial. Methods Multicenter, retrospective study. Patients treated with PnR for RRD between 2021 and 2023 and a follow-up of at least 6 months were included. Single-procedure anatomical success, final anatomical success, complications, causes of failures, best corrected visual acuity (BCVA) after surgery, and the vision-related quality of life using the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were reported. Results A total of 76 eyes of 76 patients were included. Mean age was 60 ± 8.1 years. Primary anatomic reattachment was achieved by 84.3% of patients and final anatomical reattachment after pars plana vitrectomy was obtained in 100% of patients. BCVA improved from 0.32 (20/40) to 0.04 (20/20) logMar (p

Abstract The purpose of the study was to detect Hard Exudates (HE) and classify Disorganization of Retinal Inner Layers (DRIL) implementing a Deep Learning (DL) system on optical coherence tomography (OCT) images of eyes with diabetic macular edema (DME). We collected a dataset composed of 442 OCT images on which we annotated 6847 HE and the presence of DRIL. A complex operational pipeline was defined to implement data cleaning and image transformations, and train two DL models. The state-of-the-art neural network architectures (Yolov7, ConvNeXt, RegNetX) and advanced techniques were exploited to aggregate the results (Ensemble learning, Edge detection) and obtain a final model. The DL approach reached good performance in detecting HE and classifying DRIL. Regarding HE detection the model got an AP@0.5 score equal to 34.4% with Precision of 48.7% and Recall of 43.1%; while for DRIL classification an Accuracy of 91.1% with Sensitivity and Specificity both of 91.1% and AUC and AUPR values equal to 91% were obtained. The P-value was lower than 0.05 and the Kappa coefficient was 0.82. The DL models proved to be able to identify HE and DRIL in eyes with DME with a very good accuracy and all the metrics calculated confirmed the system performance. Our DL approach demonstrated to be a good candidate as a supporting tool for ophthalmologists in OCT images analysis.

Abstract Background To report a case of cataract surgery in unintentional Ozurdex (Allergan, Inc., Irvine, California, USA) injection into the lens. Case presentation A 82-years old man reporting decreased visual acuity in his right eye came to our Ophthalmology service. Due to the clinical history, and on the basis of ophthalmoscopic and imaging examinations diabetic macular edema was diagnosed. Thus, intravitreal dexamethasone implant was scheduled and therefore performed. The following day Ozurdex appeared to be located into the lens. After careful evaluation and strict follow up examinations, due to the risks associated with the presence of the implant into the lens, phacoemulsification with Ozurdex removal and intraocular lens (IOL) implantation was scheduled and performed. Conclusions In this case report we reported the surgical management of accidental into-the lens dexamethasone implant carefully taking into account the dexamethasone pharmacokinetic.

IntroductionDiabetic retinopathy (DR) is a microvascular complication of diabetes in which neurodegeneration has been recently identified as a driving force. In the last years, mesenchymal stromal cells (MSCs) and neurotrophins like Nerve Growth Factor (NGF), have garnered significant attention as innovative therapeutic approaches targeting DR-associated neurodegeneration. However, delivering neurotrophic factors directly in the eye remains a challenge. Hence, this study evaluated the effects of MSCs from human amniotic fluids (hAFSCs) and recombinant human NGF (rhNGF) delivered by human corneal lenticule (hCL) on a high glucose (HG) induced ex vivo model simulating the molecular mechanisms driving DR.MethodsPorcine neuroretinal explants exposed to HG (25 mM for four days) were used to mimic DR ex vivo. hCLs collected from donors undergoing refractive surgery were decellularized using 0.1% sodium dodecyl sulfate and then bioengineered with hAFSCs, microparticles loaded with rhNGF (rhNGF-PLGA-MPs), or both simultaneously. Immunofluorescence (IF) and scanning electron microscopy (SEM) analyses were performed to confirm the hCLs bioengineering process. To assess the effects of hAFSCs and rhNGF, bioengineered hCLs were co-cultured with HG-treated neuroretinal explants and following four days RT-PCR and cytokine array experiments for inflammatory, oxidative, apoptotic, angiogenic and retinal cells markers were performed.ResultsData revealed that HG-treated neuroretinal explants exhibit a characteristic DR-phenotype, including increased level of NF-kB, NOS2, NRF2 GFAP, VEGFA, Bax/Bcl2 ratio and decreased expression of TUBB3 and Rho. Then, the feasibility to bioengineer decellularized hCLs with hAFSCs and rhNGF was demonstrated. Interestingly, co-culturing hAFSCs- and rhNGF- bioengineered hCLs with HG-treated neuroretinal explants for four days significantly reduced the expression of inflammatory, oxidative, apoptotic, angiogenic and increased retinal markers.ConclusionOverall, we found for the first time that hAFSCs and rhNGF were able to modulate the molecular mechanisms involved in DR and that bioengineered hCLs represents a promising ocular drug delivery system of hAFSCs and rhNGF for eye diseases treatment. In addition, results demonstrated that porcine neuroretinal explants treated with HG is a useful model to reproduce ex vivo the DR pathophysiology.

Abstract Animal models have demonstrated that structural changes affect the macula during peripheral rhegmatogenous retinal detachment. This study aimed to assess photoreceptors, retinal and choriocapillaris perfusion in non-macula involving rhegmatogenous retinal detachment by analyzing en-face images from structural OCTA segmented at the ellipsoid zone (EZ) level, calculating (1) “normalized” reflectivity as a surrogate biomarker of photoreceptor damage (2) perfusion density (PD), vessel length density (VLD) and vessel diameter index (VDI) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) (3) perfusion density of choriocapillaris (PDCC). Twenty-one eyes affected by macula-on rhegmatogenous retinal detachment (RRD) were enrolled at the University “G. d’Annunzio”, Chieti-Pescara. The fellow unaffected eye was used as control. The mean age at the onset of RRD was 60.09 ± 10.22 (range 34–83). Compared with fellow eyes, we found lower EZ “normalized” reflectivity in macula-on (0.42 ± 0.15 in fellow eyes and 0.31 ± 0.09 in macula on p = 0.004). The affected eye was also characterized by impaired perfusion in SCP (17.26 ± 3.34% in macula on and 20.56 ± 3.62% in the fellow eye p = 0.004) and CC (50.21 ± 6.20% in macula on the eye and 57.43 ± 6.20% in the fellow eye p = 0.004). Macula-on rhegmatogenous retinal detachment has subclinical changes in photoreceptors, SCP, and CC. Future longitudinal studies should evaluate if early changes could impact post-operative macular function.

Abstract Introduction We conducted a cross-sectional study to compare macular pigment optical density (MPOD) in eyes with idiopathic macular holes with bumpy (bbMH) and smooth borders (sbMH) and to assess the relation between MPOD and optical coherence tomography findings. Thirty eyes from thirty patients affected by idiopathic macular hole were studied. Methods All patients underwent SD-OCT and macular pigment optical density (MPOD) analysis. Comparison between the two border phenotypes were estimated at baseline, as well as the differences in MPOD, minimum and basal hole diameter, tractional hole index (THI), macular hole index (MHI), diameter hole index (DHI), and ELM integrity metrics between the two groups. Results The mean MPOD was 0.09 ± 0.08 in bbMHs and 0.16 ± 0.11 in sbMHs (p = 0.010). Correlation analysis between MPOD and minimum hole diameter revealed a negative association (rho = − 0.707, p = 0.008) in bbMH and a positive association (rho = 0.702, p = 0.019) in sbMH. MPOD and basal diameter were negatively correlated in bbMH (rho = − 0.77, p = 0.001) and positively correlated in sbMH (rho = 0.675, p = 0.019). Indeed, MPOD is negatively correlated with THI and MHI in sbMH (rho = − 0.684 p = 0.019; rho = − 0.665 p = 0.019, respectively) and positively correlated in bbMH (rho = 0.593 p = 0.037; rho = 0.658 p = 0.018, respectively). Conclusions MPOD is significantly reduced in bbMHs compared to sbMHs. The two border phenotypes also differ for tractional and tangential indexes, possibly reflecting a different pathogenesis. Further studies are needed to understand the prognostic role of MPOD.

Background and Objectives: The aim of the present study is to analyze choroidal and choriocapillaris structural and functional changes in eyes affected by Central serous chorioretinopathy after Photodynamic Therapy (PDT) and Subthreshold Micropulse laser (SML) treatment. Materials and Methods: Forty-two eyes of forty-two patients were analyzed in this observational study. Twenty-four patients underwent SML treatment, whereas eighteen patients were treated with PDT. Examinations were performed at baseline and after 3 months of treatment. Main outcome measures were: Best corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), pigment epithelial detachment (PED) presence and maximum height (PEDMH), and choroidal vascularity index (CVI) measured by means of Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) Optical coherence tomography (OCT) and choriocapillaris flow voids (CCFV) measured on Optical Coherence Tomography Angiography (OCT-A) platform PLEX Elite 9000 device (Carl Zeiss Meditec Inc., Dublin, CA, USA). Results: Changes in BCVA were registered in both groups over time (p < 0.001). Structural changes in terms of reduced CMT and PED presence were noted in the two groups at follow-up (p < 0.001 and p = 0.001, respectively). Structural and functional choroidal changes were found in the two groups with reduced CCT and CVI over time (p = 0.004 and p = 0.007, respectively), with significant differences between the two groups for CVI parameter (p = 0.001). CCFV increased over time in the PDT group and decreased in the SML group. Conclusions: PDT and SML are effective approaches in CSC eyes and are able to improve structural and functional parameters over time. Choroidal and choriocapillaris parameters are promising biomarkers able to monitor disease course, showing greater impact of PDT on choroid-choriocapillaris complex over time.

Abstract This study aimed at predicting the filtration surgery (FS) outcome using a machine learning (ML) approach. 102 glaucomatous patients undergoing FS were enrolled and underwent ocular surface clinical tests (OSCTs), determination of surgical site-related biometric parameters (SSPs) and conjunctival vascularization. Break-up-time, Schirmer test I, corneal fluorescein staining, Meibomian gland expressibility; conjunctival hyperemia, upper bulbar conjunctiva area of exposure, limbus to superior eyelid distance; and conjunctival epithelial and stromal (CET, CST) thickness and reflectivity (ECR, SCR) at AS-OCT were considered. Successful FS required a 30% baseline intraocular pressure reduction, with values ≤ 18 mmHg with or without medications. The classification tree (CT) was the ML algorithm used to analyze data. At the twelfth month, FS was successful in 60.8% of cases, whereas failed in 39.2%. At the variable importance ranking, CST and SCR were the predictors with the greater relative importance to the CART tree construction, followed by age. CET and ECR showed less relative importance, whereas OSCTs and SSPs were not important features. Within the CT, CST turned out the most important variable for discriminating success from failure, followed by SCR and age, with cut-off values of 75 µm, 169 on gray scale, and 62 years, respectively. The ROC curve for the classifier showed an AUC of 0.784 (0.692–0.860). In this ML approach, CT analysis found that conjunctival stroma thickness and reflectivity, along with age, can predict the FS outcome with good accuracy. A pre-operative thick and hyper-reflective stroma, and a younger age increase the risk of FS failure.

To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment–optical coherence tomography (AS-OCT). Forty-two candidate patients for MP-TLT were consecutively enrolled and underwent AS-OCT at baseline and after six months. MP-TLT success was defined as an intraocular pressure (IOP) reduction by one-third. The main outcome measures were the mean superior (S-), inferior (I-), and total (T-) intra-scleral hypo-reflective space area (MISHA: mm2) and scleral reflectivity (S-SR, I-SR, T-SR; arbitrary scale) as in vivo biomarkers of uveoscleral aqueous humor (AH) outflow. The IOP was the secondary outcome. The relations between the baseline-to-six months differences (D) of DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, DT-SR, and DIOP, were investigated. At 6 months, the median IOP reduction was 21% in the failures and 38% in the successes. The baseline S-MISHA, I-MISHA, and T-MISHA did not differ between the groups, while S-SR and T-SR were higher in the successes (p < 0.05). At six months, successful and failed MP-TLTs showed a 50% increase in S-MISHA (p < 0.001; p = 0.037), whereas I-SR and T-SR reduced only in the successes (p = 0.002; p = 0.001). When comparing DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, and DT-SR, there were no significant differences between the groups. In the successful procedures, DIOP was positively correlated with DT-MISHA and DI-MISHA (ρ = 0.438 and ρ = 0.490; p < 0.05). MP-TLT produced potentially advantageous modifications of the sclera in refractory glaucoma. Given the partial correlation between these modifications and post-treatment IOP reduction, our study confirmed that the activation of the uveoscleral AH outflow route could significantly contribute to the IOP lowering after MP-TLT.

Abstract To compare the anatomical/functional changes after navigated subthreshold pulse laser (SML) and oral eplerenone therapy for chronic central serous chorioretinopathy (cCSC). A total of 36 eyes of 36 patients suffering from cCSC treated with navigated SML (Navilas® 577s; OD-OS GmbH, near Berlin, Germany) (18 eyes, SML group) and oral eplerenone (18 eyes, eplerenone group) were enrolled in this retrospective study. Main outcome measures during a 3-month follow up period included changes of best corrected visual acuity (BCVA), central macular thickness (CMT), foveal subretinal fluid thickness (FSRFT), and subfoveal choroidal thickness (SFCT). At baseline average duration of symptoms was 6.8 ± 0.6 months in SML group and 6.4 ± 0.9 months in eplerenone group (p = 0.127). Mean BCVA, CMT and FSRFT changed significantly over time (p

We report an atypical presentation of Beauveria bassiana keratitis which unusually presented in a 85-year-old patient with a corneal ulcer with an anterior segment inflammation and hypopyon. Despite negative culture and unspecific results from panfungal PCR-based sequencing, the patient was treated for a presumed fungal infection. Following clinical deterioration an emergency surgical intervention with apposition of a corneal patch was performed. Infection resolution was achieved following the introduction of systemic voriconazole to the topical one.

Aim: To investigate the efficacy and safety of micropulse laser trabeculoplasty (MLT) using a 577 nm yellow wavelength laser randomly assigned to either 1500 or 1000 mW in patients with primary open-angle glaucoma (POAG). Methods: A prospective, double-blinded study of POAG patients was performed in a single center. MLT treatment included a 577 nm micropulse laser (IRIDEX IQ 577TM, IRIDEX, Mountain View, CA, USA) to 360° of the trabecular meshwork at randomly assigned varying powers: 1500 mW in one eye (MLT 1500 group) and 1000 mW in the other (MLT 1000 group). Best-corrected visual acuity (BCVA), intraocular pressure (IOP), corneal central thickness (CCT), and endothelial cell count (ECC) were evaluated at baseline (T0), post-operative 1 h (T1), 24 h (T2), 1 month (T3), 3 months (T4), and 6 months (T5) after laser treatment. Topical medications were assessed pre-treatment and at T4. Results: Among the 18 eyes included, we achieved a success rate (IOP reduced > 20%) in 77% of sampled eyes. In particular, IOP reduced at T2 and T3 with both MLT 1500 and 1000 without any significant differences (IOP reduction 22.9% vs. 17.3%, respectively, MLT1500 vs. MLT1000 at T2). The IOP returned to baseline values at T4 and T5 in both groups, with a reduction in topical medications administered from 2.5 ± 1.1 to 2.0 ± 1.2 to the 1500 mW group and from 2.4 ± 1.0 to 1.9 ± 1.0 to the 1000 mW group. At 1 h post-laser treatment, a transient IOP spike was registered among the MLT1500 group. There were no differences in CCT and ECC at any timepoint according to the laser powers. Conclusions: Over a 6-month follow-up period, 577 nm MLT at either 1500 or 1000 mW reduces IOP, enabling a stable reduction in the number of topical medications required for patients treated for POAG without any significant difference in terms of effectiveness and safety.

Purpose: The purpose of this study was to analyze choroidal and retinal vascular alterations of both the macula and midperiphery areas in patients hospitalized for COVID-19 infection complicated with pneumonia within 30 days from discharge. Methods: A total of 46 eyes of 23 subjects with a history of symptomatic COVID-19 infection and recent hospitalization for pneumonia were enrolled in this observational study. Patients had not been previously vaccinated against COVID-19. A group of patients homogenous for age and sex was enrolled as controls. Microvascular retinal and choroidal features of the enrolled patients were studied with widefield optical coherence tomography angiography (OCT-A). Perfusion parameters in terms of the vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the choroidal vascularity index (CVI) on enhanced depth imaging (EDI) mode OCT scans were analyzed. Results: Our cohort of patients showed a trend of reduction in VD, significantly in the SCP VD of the superior and inferior midperiphery sectors, whereas the CVI did not show significant differences between the cases and controls. Moreover, a positive correlation between CVI and vessel density in the deep capillary plexus in the macular area (VD-DCP-MAC) was found. Conclusion: The systemic disease due to COVID-19 can also involve the retina and choroid with multiple mechanisms: ischemic and inflammatory. Our study showed changes in perfusion occurring in the eyes of patients with a recent hospitalization for COVID-19 complicated with pneumonia and without any possible ocular effect due to the vaccines. There is still the need to better comprise how long COVID-19 actually affects vascular changes in the eye.

Abstract Diabetic retinopathy (DR) is a leading cause of vision loss and disability. Effective management of DR depends on prompt treatment and would benefit from biomarkers for screening and pre-symptomatic detection of retinopathy in diabetic patients. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which are released in the bloodstream and may serve as biomarkers. Little is known on circulating miRNAs in patients with type 2 diabetes (T2DM) and DR. Here we show that DR is associated with higher circulating miR-25-3p (P = 0.004) and miR-320b (P = 0.011) and lower levels of miR-495-3p (P

Nerve growth factor (NGF) is the best characterized neurotrophin, and it is known to play an important role in ocular homeostasis. Here, we demonstrated the expression of NGF receptors in adult zebrafish retina and optimized a light-induced retina degeneration (LID) zebrafish model that mimics human cone-rod disorders, demonstrating that intravitreal (IV) administration of rhNGF can boost zebrafish retinal regeneration in this model. Adult zebrafish retinae exposed to 60 h of light irradiation (60 h LID) displayed evident reduction of outer nuclear layer (ONL) thickness and cell number with presence of apoptotic cells. Retinal histologic evaluation at different time points showed that IV therapeutic injection of rhNGF resulted in an increase of ONL thickness and cell number at late time points after damage (14 and 21 days post injury), ultimately accelerating retinal tissue recovery by driving retinal cell proliferation. At a molecular level, rhNGF activated the ERK1/2 pathway and enhanced the regenerative potential of Müller glia gfap- and vim-expressing cells by stimulating at early time points the expression of the photoreceptor regeneration factor Drgal1-L2. Our results demonstrate the highly conserved nature of NGF canonical pathway in zebrafish and thus support the use of zebrafish models for testing new compounds with potential retinal regenerative properties. Moreover, the pro-regenerative effects of IV-injected NGF that we observed pave the way to further studies aimed at evaluating its effects also in mammals, in order to expedite the development of novel rhNGF-based therapeutic approaches for ophthalmological disorders.

Normal tension glaucoma (NTG) remains a therapeutic challenge for the ophthalmologist since there are no effective therapies as the main therapeutic target, i.e., the intraocular pressure (IOP) increase, is missed. We report on the effectiveness of two neuroprotective molecules (ultrapure citicoline plus homotaurine), in combination with a topical hypotensive approach, in the management of NTG in a long-term follow-up (30 months). A 38-year-old Caucasian woman with no significant medical history and a diagnosis of NTG, after an extensive 30-month treatment with oral dietary supplement containing ultrapure citicoline 500 mg, homotaurine 50 mg and vitamin E once per day and topical glaucoma medication (brimonidine + brinzolamide drops twice per day), presented a significantly improved automated 24-2 visual field with a controlled tonometric measurement associated with a stabilization of retinal fiber layer and ganglion cells at OCT examination with patient satisfaction. This finding suggests that ultrapure citicoline together with homotaurine and vitamin E, through a synergistic neuroprotective effect, could be a promising approach in the management of NTG.

Background: The aim of this study was to assess long-term macular vascular changes and their correlation with functional recovery in patients successfully treated for Macula-ON and Macula-OFF rhegmatogenous retinal detachment (RRD). Methods: This retrospective observational study included 82 eyes of 82 patients who received primary successful retinal detachment surgery, 33 Macula-ON and 49 Macula-OFF. Superficial and deep capillary plexuses (SCP and DCP) were evaluated by optical coherence tomography angiography (OCTA), and were correlated with visual acuity (VA), surgical technique and tamponade at 12 months after surgery. The fellow eyes were used as controls. Results: At 12-month follow-up, there was a significant decrease in the vessel density (VD) in the SCP in the operated eyes compared to control eyes (p < 0.05) in both the Macula-ON and Macula-OFF groups. Vessel length density (VLD) decrease in SCP was more extended in the Macula-OFF group. No difference in the DCP perfusion parameters was found, compared to controls. Subgroup analysis dependent on the type of surgery or tamponade showed no significant differences of VD and VLD. An inverse correlation was found between the SCP VD and the duration of silicone oil (SO) tamponade (p = 0.039). A significant correlation was observed between parafoveal SCP VD and final best corrected visual acuity (BCVA) (p = 0.028). The multivariate linear regression analysis showed that only the type of tamponade was significantly correlated with the final BCVA in the Macula-ON group (p = 0.004). Conclusions: Our study described long-term perfusion changes in RRD after surgery, with lower SCP VD and VLD in the operated eyes compared to the fellow ones, not influenced by type of surgery or tamponade. The choice of tamponade and SO removal timing may affect functional outcomes, especially in Macula-ON RRD. In conclusion, such functional and perfusion changes can be considered biomarkers that highlight the relevance of careful management of this sight-threatening disease.

Purpose: We report a case of a highly myopic patient who presented a serous macular detachment at 24 hours after uncomplicated cataract surgery. Observations: Surprisingly, after six days from surgery, a reabsorption of the detachment was noticed and the macular area returned to be anatomically normal without any surgical intervention. This early postoperative complication could be caused by changes in the vitreoretinal interface and ocular fluid dynamics or to a rupture of blood-retinal barriers due to postoperative inflammation. Conclusions and importance: Our case reports on the occurrence of an early transient macular detachment after uneventful cataract surgery in a highly myopic eye. This finding suggests the importance of an OCT-based control in the immediate postoperative hours.

Background and Objectives: The aim of this study was to investigate the impact of oral administration of the combination of astaxanthin (AXT), lutein, folic acid, vitamin D3, and bromelain with antioxidants on choroidal blood flow in patients with age-related intermediate macular degeneration (AMD). Materials and Methods: Patients affected by intermediate AMD and treated with daily oral nutritional supplement with AXT, bromelain, vitamin D3, folic acid, lutein, and antioxidants for a period of at least 6 months were included in this retrospective study. A control group homogenous for age and sex was also included in the analysis. All participants underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA) evaluation. Outcome measures were choroidal thickness (CHT) and choriocapillary vessel density (CCVD) after six months of AXT assumption. Results: CCVD values showed statistically significant difference between cases and controls at baseline (p < 0.001) and in the cases during follow-up (p < 0.001). The CHT measurements showed statistically significant difference between cases and controls (p = 0.002) and in the cases during follow-up (p < 0.001). Conclusions: The combined use of structural OCT and OCTA allows for a detailed analysis in vivo of perfusion parameters of the choriocapillaris and choroid and evaluation of changes of choroidal blood flow after oral nutritional supplements that affect blood flow velocity.

Purpose: We report a case of a patient with a known hereditary spherocytosis who developed a bilateral macular hemorrhage in concurrence with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related respiratory syndrome. Observations: Blood tests showed severe hemolytic anemia. Interestingly, the peripheral blood smear demonstrated a mixed pathogenesis of the hemolytic process (cold-agglutinin-mediated and non-immune-mediated due to spherocytosis). Conclusions and Importance: We argue that SARS-CoV-2 could have triggered the hemolytic process, which led to retinal hemorrhages due to endothelial anoxia from the low oxygen carrying capacity.

PurposeTo assess the different impact of two enface OCTA image simultaneously acquired by means of a new prototype of Spectral-Domain Optical Coherence Tomography Angiography (SD-OCTA) on quantitative retinal vascular metrics.MethodsIn this prospective observational cross-sectional study 28 healthy subjects were enrolled. Macular (3x3 mm) OCTA images were acquired for all participants using Solix Fullrange OCT (Optovue Inc, Freemont CA, USA). The main outcome measurements were: Perfusion density (PD), vessel length density (VLD), and vessel diameter index (VDI) of both superficial capillary plexus (SCP) and deep capillary plexus (DCP), and choriocapillaris (CC) total flow-deficits area. Quantitative retinal vascular metrics were measured on binarized and skeletonized OCTA images by comparing not averaged and fast automated multiple averaged en face OCTA images.ResultsIn both SCP and DCP, PD significantly increased (p = 0,005 and p = 0,030, respectively), and VLD significantly decreased (pConclusionsIn this study, we found a significant difference of quantitative retinal metrics by comparing two different image acquisition modes using a novel and fully automated averaging OCTA system in young healthy subjects.

Purpose. To evaluate capsulotomy shape and posterior capsule opacification (PCO) during an 18-month follow-up for bimanual femtosecond laser-assisted cataract surgery (FLACS). Methods. 74 eyes operated by a well-trained surgeon with bimanual FLACS technique using low-energy LDV Z8 (Ziemer Ophthalmic Systems AG, Port, Switzerland) were included in the study. The follow-up period was 18 ± 2 months. Another 91 eyes, which underwent standard bimanual microincision cataract surgery (B-MICS), served as a control group. In all cases, a BunnyLens AF (Hanita Lenses, Israel) intraocular lens was implanted in the bag. A digital image of the capsule with slit-lamp retroillumination was performed in all patients at 18 months of follow-up. Image analysis software (ImageJ) was used to evaluate the shape of the capsulotomy in terms of diameter, area, and circularity. PCO score was evaluated using EPCO 2000 software. Best corrected visual acuity (BCVA) and endothelial cell count (ECC) were evaluated before and after surgery at 1 and 18 ± 2 months. Results. At 18 months, mean capsulotomy diameter was 5.34 ± 0.21 mm while capsulorhexis was 5.87 ± 0.37 mm (p

Purpose. To assess long-term efficacy of a multiple therapy approach in the treatment and management of unilateral stage 3 Coats disease with exudative retinal detachment. Methods. 2 eyes of 2 young patients suffering from unilateral stage 3 Coats disease underwent a multiple therapy approach consisting of surgical drainage of exudative subretinal fluid + one simultaneous and up to one subsequent intravitreal injection of bevacizumab + multiple (up to 3) laser photocoagulation sessions of retinal nonperfusion areas and leaking Coats vasculature. Results. Complete reabsorption of SRF and retinal reattachment were observed in both cases over the follow-up. In no cases, we observed progression to phthisis bulbi. No bevacizumab-related complications were observed. Epiretinal membrane onset was detected in one eye at the end of follow-up. Conclusion. The management and treatment of this rare and degenerative disease in young subjects are still a challenge. The described technique is less invasive than conventional intraocular surgery and may be preferable to halt the devastating progression of the disease.

Aim. This study aims to evaluate the morphology of ganglion cell complex (GCC) along with functional outcomes in patients undergoing vitrectomy with ILM peeling and macular abrasion with Tano diamond dusted membrane scrapers (DDMS) for three different stages of the idiopathic macular hole (IMH). Methods. This retrospective study was conducted between April 2019 and December 2019. 33 patients with IMH were included and divided into three groups: stage I, stage II, and stage IV. All patients were subjected to vitrectomy with ILM peeling. Gentle and vigorous macular abrasion was additionally performed for stage II and stage IV patients, respectively. The best-corrected visual acuity (BCVA), GCC thickness (measured by spectral domain-optical coherence tomography (SD-OCT)), and photopic contrast sensitivity (Rodenstock CV 900 Chart Panel) were determined before surgery and at 1- and 3-month follow-ups. Results. Closure of MH was achieved in all the patients. The difference between the preoperative and one- and three-month postoperative values of BCVA was statistically significant in the three groups (P

Abstract The aim of this work was to investigate the changes in aqueous humor cytokine levels after intravitreal injection of aflibercept in diabetic macular edema (DME) and to evaluate the relationship between cytokines modifications and central macular thickness (CMT) and retinal/choroidal vascular changes using structural and functional optical coherence tomography (OCT). Aqueous concentrations of 38 cytokines were measured via multiplex bead assay. In addition, spectral domain OCT and OCT angiography with SSADA software (XR Avanti® AngioVue) were performed at baseline and after intravitreal injections. VEGF, IL-6, IL-5, IL-1β, Eotaxin, GRO, IL-12p40, IL-12p70, IL-1RA, Flt-3L and IP-10 showed a statistically significant decrease through the follow-up (p

(1) Background: The aim of this observational comparative study was to investigate early retinal vascular and functional changes in patients undergoing vitreoretinal surgery for idiopathic epiretinal membrane (iERM) or macular hole (MH) using a widefield swept-source optical coherence tomography angiography (WSS-OCTA). (2) Methods: Forty one diseased eyes were enrolled in the study. Twenty three eyes with iERM diagnosis (ERM group) underwent 25-gauge vitrectomy with inner limiting membrane (ILM) and MER peeling, while eighteen eyes with MH (MH group) underwent 25-gauge vitrectomy with inverted flap technique. Functional and anatomical/perfusion parameters were evaluated pre- and postoperatively in all eyes by means of WSS-OCTA system, microperimetry (MP3), best corrected visual acuity assessment, central macular thickness (CMT) and MH diameter calculation. For each eye, 12 × 12 mm OCTA volume scans were acquired by a retinal specialist and a semi-automated algorithm was used for a quantitative vessel analysis of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC). In detail, perfusion density (PD) of the SCP, DCP and CC was evaluated in four circles (one central in the macular area of 5 mm diameter; three midperiphery circles (temporal, superior and inferior) of 3 mm). In addition, the vessel length density (VLD) of the SCP and DCP for the same circles was quantified. (3) Results: In the MH group, PD of the SCP significantly increased in the macular area (p = 0.018) and in the superior ring (p = 0.016); PD of the DCP significantly increased in the macular area (p = 0.015) and in the superior and inferior ring (p = 0.016) 3 months after surgery. In the ERM group, PD of the SCP and DCP significantly increased in the macular area and superior ring, respectively (p = 0.001; p = 0.032), 3 months after surgery. During follow-up there was a significant improvement in terms of functional (Best corrected visual acuity, p = 0.007 and p = 0.029; microperimetry ((MP3) 10°, p = 0.003 and p = 0.004; MP3 2°, p = 0.028 and p = 0.003 in MH group and ERM group respectively) and anatomical parameters (CMT, p = 0.049 in ERM group; hole complete closure in MH group). (4) Conclusions: After vitreoretinal surgery, early retinal vascular and functional changes can be promptly observed and quantified to monitor and potentially predict surgery outcomes. Widefield OCTA devices allow for a detailed microvasculature analysis of retina and choriocapillaris in the macular area and in the periphery, showing a different behaviour of retinal sectors in two distinct vitreoretinal disorders.

AIM: To investigate foveal avascular zone (FAZ) and parafoveal vessel densities (PRVD) by means of optical coherence tomography angiography (OCTA) in diabetic patients with or without diabetic retinopathy (DR) and to assess the reproducibility of FAZ and PRVD measurements. METHODS: Sixty diabetic patients (60 eyes) with different stage of DR (graded according to the International Clinical Severity Scale for DR) and 20 healthy subjects underwent FAZ area and PRVD measurements using OCTA by two experienced examiners. FAZ area in all patients was also assessed using fluorescein angiography (FA). RESULTS: In subject with proliferative DR and with moderate-severe non proliferative DR, FAZ area was significantly increased compared to healthy controls (P=0.025 and P=0.050 respectively measured with OCTA and P=0.025 and P=0.048 respectively measured with FA). OCTA showed significantly less inter-observer variability compared to FA. Concordance correlation coefficient (CCC) for FAZ area measurements was 0.829 (95%CI: 0.736-0.891) P

The aim of our study is to evaluate the serum circulating levels of some miRNA, such as hsa-let-7b-5p, hsa-let-7a-5p, hsa-miR-320b, hsa-miR-23a-3p, hsa-miR-27a-3p, hsa-miR-15a-5p, and hsa-miR-495-3, in diabetic patients without diabetic retinopathy (DR), diabetic patients with DR, and, healthy subjects in order to find reliable and reproducible biomarkers for DR. A total of 45 subjects underwent serum sampling for miRNAs evaluation and a complete ophthalmologic examination, including microperimetry and widefield swept source optical coherence tomography angiography (OCTA). Total circulating RNA was isolated from patients using the miRNeasy Serum/Plasma Kit. Serum miRNA expression levels were significantly different in the three groups. In detail, circulating hsa-miR-15a-5p levels were significantly reduced in both diabetic patients without DR and diabetic patients with DR (p = 0.027). Serum hsa-miR-495-3p was lower in diabetic patients with DR and diabetic patients without DR (p = 0.049). Hsa-miR-23a-3p serum expression levels were significantly lower in diabetic patients with DR and diabetic patients without DR (p = 0.013). Significant associations of miRNAs with anatomical/perfusion parameters and functional parameters were observed in the diabetic groups. We find evidence of damage in progression biomarkers in DR that are evidently early in patients with diabetes without DR. Serum miRNAs levels are considered to have strong potential as a novel biomarker for the early detection of DR in subjects suffering from diabetes and could represent noninvasive target therapies to block the progression of the disease at the early stages.

Optical coherence tomography angiography (OCTA) is a non-invasive diagnostic instrument that has become indispensable for the management of age-related macular degeneration (AMD). OCTA allows quickly visualizing retinal and choroidal microvasculature, and in the last years, its use has increased in clinical practice as well as for research into the pathophysiology of AMD. This review provides a discussion of new technology and application of OCTA in intermediate and late AMD.

Drug delivery into the vitreous chamber remains a great challenge in the pharmaceutical industry due to the complex anatomy and physiology of the eye. Intravitreal injection is the mainstream route of drug administration to the posterior segment of the eye. The purpose of this review is to assess the current literature about the widening use of the intravitreal 0.7 mg dexamethasone (Dex) implant, and to provide a comprehensive collection of all the ocular disorders that benefit from Dex administration. Although anti-vascular endothelial growth-factors (VEGFs) have been largely indicated as a first-choice level, the Dex implant represents an important treatment option, especially in selected cases, such as vitrectomized eyes or patients in whom anti-VEGF failed or are contraindicated. In this article, the safety profile as well as the list of the possible complications related to intravitreal Dex injection are also discussed.

Background and Objectives: the aim of the study was to evaluate the repeatability and reproducibility of optical microangiography (OMAG)-based optical coherence tomography angiography (OCTA) in the optic nerve head (ONH) and radial peripapillary capillary (RPC) perfusion assessment of healthy eyes. Materials and Methods: in this observational study, a total of 40 healthy subjects underwent ONH evaluation, using an OMAG-based OCTA system at baseline (T0), after 30 min (T1), and after 7 days (T2). The main outcome measures were the vessel density (VD) and flux index (FI) of the RPCs, as well as peri-papillary retinal nerve fibre layer (pRNFL) thickness. The analysis was performed by two observers independently. The coefficient of repeatability (CR), within the subject coefficient of variation (CVw) and intrasession correlation coefficient (ICC), to evaluate intrasession repeatability of measurements was calculated for each observer. Results: the high intrasession and intersession repeatability and reproducibility were assessed in the two observers for all three outcome measures. Of note, the CRs for the first and the second observer were 0.011 (95% confidence interval (CI) 0.009−0.014) and 0.016 (95% CI 0.013−0.020) for FI, 0.016 (95% CI 0.013−0.021) and 0.017 (95% CI 0.014−0.021) for VD, and 2.400 (95% CI 1.948−3.092) and 3.732 (95% CI 3.064−4.775) for pRNFL thickness, respectively. The agreement between them was excellent for pRNFL assessment and very good for FI and VD. Conclusion: OCTA has a great potential in the accurate assessment of ONH and peri-papillary microcirculation. It allows for repeated and reproducible measurements without multiple scans-related bias, thus guaranteeing an independent operator analysis with good reproducibility and repeatability.

(1) Background: To evaluate superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), perfusion density (PD), and vessel length density (VLD) in macular and near/mid periphery regions in patients with retinitis pigmentosa (RP) using widefield swept source optical coherence tomography angiography (WSS-OCTA). (2) Methods: Twelve RP patients (20 eyes) and 20 age-matched subjects (20 eyes) were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). Quantitative analysis was performed in the macular and peripheral regions. The main outcome measures were SCP, DCP, CC, PD, and VLD in central and peripheral areas. (3) Results: Mean visual acuity, central macular thickness, and microperimetry were significantly reduced in RP patients compared to normal subjects (p < 0.05). The perfusion density and VLD of SCP, DCP, and CC were significantly reduced in RP patients compared to normal controls both in the central and peripheral retina (p < 0.05). A significant direct correlation was found in RP patients between PD of the 1.5 mm central retina both in DCP and CC and microperimetry at 4° and 8°. (4) Conclusions: Widefield SS-OCTA shows an impairment of retinal and choroidal perfusion density and vessel length density in central and peripheral retina of RP patients. The reduction of flow features correlates with the macular function.

PurposeTo investigate radial peripapillary capillary (RPC) network in patients affected by retinitis pigmentosa (RP).MethodsEleven patients (22 eyes) with previous diagnosis of RP and 16 age-matched healthy subjects (16 eyes) were enrolled. The diagnosis of RP was made based on both clinical features and electrophysiological examination. All patients underwent a complete ophthalmologic examination, including optical coherence tomography angiography and visual field (VF). The primary outcomes were the RPC vessel density in the peripapillary and disk areas; the secondary outcomes were the peripapillary retinal nerve fiber layer (RNFL) thickness and the mean defect at VF.ResultsA total of 19 eyes of 11 RP patients (5 males, 6 females) and 16 eyes of 16 healthy subjects (10 males, 6 females) were included for the analysis. RPC vessel density in the disk area was 46.5 ± 7.1% in the RP group and 45.4 ± 10.6% in the control group (p = 0.754). RPC vessel density in the peripapillary area was significantly reduced in the RP group after the comparison with the control group (52.5 ± 5.0 and 57.2 ± 5.1%, respectively, p = 0.011). RNFL thickness was 85.9 ± 20.4 μm in the RP group and 104.0 ± 6.4 μm in the control group (p = 0.002). RPC vessel density was significantly correlated with RNFL thickness values in RP patients, both in the disk and in the peripapillary area (Rho = 0.599 and p = 0.007 in the disk area, Rho = 0.665 and p = 0.002 in the peripapillary area, respectively).ConclusionWe showed that density of RPC is reduced in these patients in the peripapillary area. Moreover, the RPC vessel density correlates with the RNFL thickness.

A rotating polarimetric 90°-cross linear-filter interferometry system was used to detect the morphological characteristics and features of interference patterns produced in in-vivo corneal stroma in healthy human corneas of 23 subjects. The characteristic corneal isogyres presenting with an evident cross-shaped pattern, grossly aligned with the fixation axis, were observed in all patients with centers within the pupillary dark area, impeding the exact determination of the center point. During the rotational scan in 78.3% of the eyes the cross-shaped pattern of the isogyre gradually separated to form two distinct hyperbolic arcs in opposite quadrants, reaching their maximal separation at 45 degrees with respect to angle of cross-shaped pattern formation. The corneal cross and hyperbolic-pattern repeated every 90° throughout the 360° rotational scan. While the interpretation of the isogyres presents particular difficulties, two summary parameters can be extracted for each cornea: the presence/orientation of a single or two dark areas in post-processed images and isochromes. However, the development of dedicated software for semi-quantitative analysis of these parameters and enantiomorphism may become available in the near future. The possible application of polarimetric interferometry in the field of both corneal pathologies and corneal surgery may be of great interest for clinical purposes.

The ciliary body ablation is still considered as a last resort treatment to reduce the intraocular pressure (IOP) in uncontrolled glaucoma. Several ablation techniques have been proposed over the years, all presenting a high rate of complications, nonselectivity for the target organ, and unpredictable dose-effect relationship. These drawbacks limited the application of cyclodestructive procedures almost exclusively to refractory glaucoma. High-intensity focused ultrasound (HIFU), proposed in the early 1980s and later abandoned because of the complexity and side effects of the procedure, was recently reconsidered in a new approach to destroy the ciliary body. Ultrasound circular cyclocoagulation (UC3), by using miniaturized transducers embedded in a dedicated circular-shaped device, permits to selectively treat the ciliary body in a one-step, computer-assisted, and non-operator-dependent procedure. UC3 shows a high level of safety along with a predictable and sustained IOP reduction in patients with refractory glaucoma. Because of this, the indication of UC3 was recently extended also to naïve-to-surgery patients, thus reconsidering the role and timing of ciliary body ablation in the surgical management of glaucoma. This article provides a review of the most used cycloablative techniques with particular attention to UC3, summarizing the current knowledge about this procedure and future possible developments.

BACKGROUND:to assess vessel density of superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) in advanced Stargardt disease (STGD) using optical coherence tomography angiography (OCTA) and correlate these findings with macular function using pattern electroretinogram (PERG) and multifocal electroretinogram (mfERG). METHODS:Twelve patients (24 eyes) with advanced STGD underwent vessel densities and macular thickness measurements using OCTA. A control group of 24 healthy controls (24 eyes) was chosen for comparison. In the STGD group correlation between vessel density and macular thickness and between macular function and morphologic parameters were evaluated. RESULTS:Whole parafoveal vessel density (VD) of SCP was significantly lower in STGD group compared to the control group (p

This retrospective quality control study aimed at comparing resolution in patients treated with intravitreal ocriplasmin (IVO) using two injection techniques, classical injection procedure (unguided) and targeted injection using a surgical microscope with a 30-gauge 1-inch needle (guided) for the treatment of focal VMT without macular hole. The two groups presented a statistically significant difference in terms of resolution of VMT within the first month following treatment: 1/7 for the unguided group versus 6/7 for the guided group (p=0.0291). The majority of the guided group presented an earlier resolution than the single resolved case in the unguided group. The results of this preliminary study indicate that the injection of ocriplasmin closer to the site of VMT results in the resolution in a higher number of cases and that this resolution occurs in a short time interval.

Aim: The aim was to evaluate the safety and efficacy of the "cross-cylinder" technique in the correction of astigmatism. Setting and Design: A prospective interventional study from a university eye department was conducted. Material and Methods: The photoastigmatic refractive keratectomy (PARK) using the "cross-cylinder" technique was performed in 102 eyes of 84 patients with at least 0.75 D of astigmatism. The study population was divided into two groups: in the first group the preoperative astigmatic power ranged from −0.75 D to −3.00 D (group 1), in the second group it ranged from −3.25 D to −6.00 D (group 2). Group 1 included 82 eyes of 67 patients (29 males and 38 females) with a mean cylinder power of −1.90 ± 0.63 D, group 2 included 20 eyes of 17 patients (13 males and 4 females) with a mean cylinder power of -4.28 ± 0.76 D. All eyes were targeted for emmetropia. The results were evaluated using Calossi′s vector analysis method. Six-month postoperative outcomes are presented. Results: Six months after PARK the mean sphere for the entire cohort was +0.28 ± 0.75 D (range +2.5 to −2 D), the mean cylindrical power was +0.33 ± 0.51 D (range +2.5 to −1.25 D) and the mean spherical equivalent refraction was +0.73 ± 0.81 D (range +1.75 to −2 D). Conclusions: The cross-cylinder technique may be safely used with predictable results for the correction of astigmatism.

Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

BACKGROUND:To investigate changes in macular morphology and function after an intravitreal dexamethasone implant for diabetic macular edema (DME). METHODS:Twenty-seven eyes in 27 treatment-naive patients affected by DME were treated with intravitreal Ozurdex® injections (IVOI) and followed up 12 months to evaluate morphological and functional changes by means of best-corrected visual acuity (BCVA), microperimetry (MP1), multifocal electroretinography (mfERG), pattern electroretinography (PERG) and spectral domain optical coherence tomography (SD-OCT). RESULTS:Both BCVA and retinal sensitivity improved significantly at one month after the IVOI (p = 0.031 and p