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Background: The aim was to evaluate predictive value of baseline optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in diabetic macular edema (DME) treated with dexamethasone implant (DEXi). Methods: OCT and OCTA parameters were collected: central macular thickness (CMT), vitreomacular abnormalities (VMIAs), intraretinal and subretinal fluid (mixed DME pattern), hyper-reflective foci (HRF), microaneurysms (MAs) reflectivity, ellipsoid zone disruption, suspended scattering particles in motion (SSPiM), perfusion density (PD), vessel length density, and foveal avascular zone. Responders’ (RES) and non-responders’ (n-RES) eyes were classified considering morphological (CMT reduction ≥ 10%) and functional (BCVA change ≥ 5 ETDRS letters) changes after DEXi. Binary logistic regression OCT, OCTA, and OCT/OCTA-based models were developed. Results: Thirty-four DME eyes were enrolled (18 treatment-naïve). OCT-based model combining DME mixed pattern + MAs + HRF and OCTA-based model combining SSPiM and PD showed the best performance to correctly classify the morphological RES eyes. In the treatment-naïve eyes, VMIAs were included with a perfect fit for n-RES eyes. Conclusion: The presence of DME mixed pattern, a high number of parafoveal HRF, hyper-reflective MAs, SSPiM in the outer nuclear layers, and high PD represent baseline predictive biomarkers for DEXi treatment responsiveness. The application of these models to treatment-naïve patients allowed a good identification of n-RES eyes.

To investigate fellow eyes of newly diagnosed unilateral exudative Type 3 (T3) macular neovascularization (MNV) patients by assessing the presence and progression of a preclinical neovascular component during a 3-year follow-up.This is a longitudinal study involving three retinal referral centers. Patients affected by unilateral exudative treatment-naive T3 MNV were enrolled.Twenty-four eyes of 24 patients (79 ± 6 years old) were enrolled. Nine eyes (37%) displayed a nonexudative T3 MNV at baseline that developed exudation after a mean of 9 ± 9 months. Fifteen eyes that did not display a nonexudative Type 3 MNV at baseline. Five eyes (21%) did not display neovessels at baseline, but showed a nonexudative T3 after 13 ± 9 months, and exudation after 8 ± 3 months. Five eyes (21%) developed active exudative T3 MNV after 23 ± 9 months, with no detectable nonexudative stage at baseline. Five eyes (21%) did not show MNV, but progressed to geographic atrophy by 36 months of follow-up. Overall, T3 MNV in the fellow eye accounted for 79%, all developing exudation over 3 years of follow-up.The occurrence of a nonexudative T3 MNV is a frequent event in the fellow eye of patients newly diagnosed with unilateral exudative T3 MNV and it precedes the development of exudation over 3 years (prevalence of 37% and cumulative incidence of 79%). Optical coherence tomography angiography approach may be used to perform an early diagnosis and treatment of patients with T3 MNV.

This study assessed retinal nonperfusion area (NPA) changes after anti-VEGF treatment in proliferative diabetic retinopathy (PDR) eyes using swept-source widefield optical coherence tomography angiography (SS-WF OCTA) and investigated the relationships with the microperimetry (MP-1) functional changes observed in the same areas.This was a single-center observational case series. Seven PDR eyes naïve to treatment that received three monthly intravitreal injections of aflibercept were included. All eyes were imaged with SS-WF OCTA and MP-1 at baseline (T0) and 1 month after the third injection (T1). The regions of interest (ROIs) with evidence of NPAs at T0 OCTA images were selected. Qualitative and quantitative [perfusion density (PD) and vessel length density (VLD)] OCTA vascular changes in the selected ROIs between T0 and T1 were compared with the corresponding MP-1 functional changes [mean sensitivity (MS)].Twenty-five ROIs were selected. In 52% of the ROIs, an improvement in MS was observed at T1, which was associated with qualitative and quantitative improvement in 92.3% of NPAs by OCTA. In 32% of the ROIs, MS worsening was observed at T1, which was associated with qualitative and quantitative worsening in 75% of NPAs by OCTA. Positive correlations between MS and both PD and VLD were found. Fisher's test showed an association between the improvements in MP and VLD.An association between OCTA and MP-1 parameter changes was found. The concomitant functional and morphological improvement in half of the ROIs suggests that anti-VEGF treatment may promote retinal changes that result in a better functional response.

The study retraces the healthcare pathway of patients affected by diabetic macular edema (DME) through the direct voice of patients and caregivers by using a “patient journey” and narrative method approach. The mapping of the patient’s journey was developed by a multidisciplinary board of health professionals and involved four Italian retina centers. DME patients on intravitreal injection therapy and caregivers were interviewed according to the narrative medicine approach. Narratives were analyzed through a quali-quantitative tool, as set by the narrative medicine method. The study involved four specialized retina centers in Italy and collected a total of 106 narratives, 82 from DME patients and 24 from caregivers. The narratives reported their difficulty in identifying the correct pathway of care because of a limited awareness of diabetes and its complications. Patients experienced reduced autonomy due to ocular complications. In the treatment of diabetes and its complications, a multidisciplinary approach currently appears to be missing. DME reduces the quality of life of affected patients. The narrative medicine approach offers qualitative and emotional patient-guided information. The patient journey provides all of those involved in the management of DME with flowcharts to refer to, identifying the critical points in the healthcare journey of DME patients to improve the management of the disease.

PurposeTo explore the potential relationships between macular vascular network and different adaptive optics (AO) metrics in patients with type 1 diabetes mellitus (DM1) with no signs (NoDR) or mild non-proliferative diabetic retinopathy (NPDR).DesignObservational cross-sectional study.MethodsForty eyes of consecutive patients with DM1 (12 NoDR and 28 NPDR) and 10 healthy age-matched control subjects were included. All patients and controls were imaged using AO retinal camera and PLEX Elite 9000 optical coherence tomography (OCT) angiography (OCTA). The AO outcome measures to evaluate the cone photoreceptor mosaic characteristics were as follows: (1) Cone density (CD); (2) Linear Dispersion Index (LDi) and (3) Heterogeneity Packing Index (HPi). The OCTA outcome measures included: (1) superficial capillary plexus (SCP) perfusion density (PD); (2) deep capillary plexus (DCP) PD and (3) the choriocapillaris (CC) flow deficit percentage (FD%).ResultsNPDR group exhibited a close relationship between cone metrics and CC FD. Notably, CC FD% increase along with LDi (p=0.035), while the increasing CC FD% were associated with reducing CD (p=0.042) and the HPi (p=0.017). Furthermore, the OCTA parameters, including PD SCP and DCP, showed a significant negative correlation with CD.ConclusionsOur results demonstrated the relationship between macular perfusion at both retinal and choroidal levels and the cone mosaic in patients with DM1 interpolating swept-source-OCTA and AO metrics. In NPDR eyes, the photoreceptor damage was accompanied by CC insufficiency since the early stages of the disease.

To analyze the morphological and functional findings using microperimetry and optical coherence tomography angiography (OCTA) in patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE).This retrospective observational case series included four eyes of two patients with APMPPE. Best-corrected visual acuity range was from 20/20 to 20/250. Microperimetry and OCTA evaluation were obtained in the acute and healed phase. The OCTA images of the choriocapillaris were superimposed on the microperimetry map at the last visit.The retinal sensitivity improved between the baseline and the last visit in three out of the four eyes. At resolution phase, OCTA revealed zones with choriocapillaris flow deficit, which were associated with points of reduced retinal sensitivity.Microperimetry allows for a better evaluation of the extent of the unhealed functional defect in eyes with AMPPE. The multimodal imaging showed that structural and functional findings were associated in the resolution phase.

Purpose: Intravitreal corticosteroid implants based on sustained-release dexamethasone provide effective retinal delivery of drug for around 6 months for the treatment of diabetic macular edema (DME). As current recommendations on the management of patients with DME undergoing cataract surgery are limited, this article aims to highlight issues and provide guidance on the use of dexamethasone intravitreal implants (DEX-DDS) in patients with DME undergoing cataract surgery, based on the consensus findings of a panel of Italian experts. Methods: The panel developed a survey regarding the use of DEX-DDS in patients with DME undergoing cataract surgery, following a comprehensive literature search. The results of the survey were discussed at an experts’ meeting in September 2018, with a structured approach to determining consensus. The routine management of patients with DME undergoing cataract surgery was also developed for use as a basis of discussion to highlight current issues. Results: Eight consensus statements are presented, along with key issues that highlight controversial/outstanding issues in the use of DEX-DDS in DME patients with cataracts. Conclusion: The consensus statements can help provide practical guidance for clinicians in daily practice on the rationale, patient diagnosis and selection, and optimal management of patients with DME undergoing cataract surgery.

Introduction This study aimed to evaluate the effect of treatment with eye drops containing citicoline and vitamin B12 on changes in function of the inner retina, morphology of the inner and outer retina, and microvascular condition in patients with type 1 diabetes (DM1) with mild signs of non-proliferative diabetic retinopathy (NPDR) during 3 years of follow-up. Methods A pilot study with prospective, randomized, and double-masked design was conducted to address the aims. Twenty patients with DM1 were enrolled and randomly divided into two groups: the DC group comprising patients treated with citicoline and vitamin B12 eye drops (10 patients; mean age ± standard deviation, 46.86 ± 8.78 years) and the DP group comprising those treated with placebo (10 patients; mean age ± standard deviation, 47.89 ± 7.74 years). In the DC group, one eye of each patient was treated with citicoline and vitamin B12 eye drops (OMK2®, Omikron Italia srl, Italy, 3 drops/day), while in the DP group, it was treated with placebo (eye drops containing hypromellose 0.3%, 3 drops/day) for a 3-year period. In both groups, Humphrey Matrix frequency doubling technology (FDT), spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA), and adaptive optics (AO) were applied at baseline and 12, 24, and 36 months of the follow-up period. Results In the results of follow-up evaluation, the DC and DP groups were significantly different: Significant reduction in function in terms of 10-2 FDT mean sensitivity and in morphology reflected by an increase in inner nuclear layer thickness and decrease in other plexiform layer thickness and foveal vessel density were observed in the DP group, while no such significant changes were observed in the DC group in the long term. Conclusions This pilot study indicated that patients with DM1 with mild signs of diabetic retinopathy (DR) who underwent treatment with citicoline and vitamin B12 eye drops for a 3-year duration achieved stabilization or decreased rate of functional impairment, neuroretinal degeneration, and microvascular damage. Trial Registration ClinicalTrials.gov identifier, NCT04009980.

To assess the effect of drusen morphometric changes and choroidal vascular modifications on retinal sensitivity (RS) evaluated through microperimetry in intermediate age-related macular degeneration (iAMD).A retrospective review of 18 iAMD patients (18 eyes) with a 12-month follow-up was performed. Eye-tracked spectral-domain optical coherence tomography was obtained, with automatic segmentation of the outer retinal layer (ORL) delineating the drusen area from the external limiting membrane to Bruch's membrane and outer nuclear layer (ONL) thickness maps adjusted manually, as needed. Advanced retinal pigment epithelium analysis was also performed with a ZEISS PLEX Elite 900. Microperimetry obtained under mesopic conditions was overlaid with the corresponding thickness maps with Fiji software. The choroidal vascularity index (CVI) was calculated in the subfoveal b-scan and volumetric in the central 1-mm subfield.A reduced central ONL thickness was strongly associated with RS decline at the same region (r = 0.69, P = 0.002) and globally (r = 0.80, P0.001) at baseline, but also at 1 year in the central subfield (central: r = 0.70, P = 0.001). One-year subfoveal CVI variation, differently from volumetric CVI, directly influenced the central (r = 0.64, P = 0.004) and global RS (r = 0.59, P = 0.009), indicating that a CVI reduction negatively affected RS. A greater volumetric CVI within central 1-mm was associated with ORL thickening at 1 year (r = 0.61, P = 0.008).Progressive degeneration of the ONL is related to irreversible photoreceptor dysfunction in iAMD. Likewise, choroidal vascular modifications are associated with a significant functional decline in the central region and diffusely.

We conducted a systematic review and meta-analysis to investigate whether depression is associated with vision impairment (VI) in population-based studies in adults. MEDLINE and EMBASE were searched, from inception to June 2020. Studies were included if they provided two-by-two data for calculating the OR of association between VI and depression, or crude and/or an adjusted odds ratio (OR) with a corresponding 95% confidence interval (CI) were reported. The proportion of VI and depression was also extracted. ORs were pooled using random-effect models, proportions were pooled using random intercepts logistic regression models. Overall, 29 articles (31 studies) were included: of those, 18 studies used survey data (622,312 participants), 10 used clinical examination data (69,178 participants), and 3 used administrative databases (48,162,290 participants). The proportion of depression (95%CI) was 0.17 (0.13–0.22) overall and 0.27 (0.21–0.33) in VI subjects. The proportion of VI was 0.10 (0.07–0.16) overall and 0.20 (0.13–0.29) in depressed subjects. The association between VI and depression was direct: crude ORs were 1.89 (1.51–2.37) for survey data, 2.17 (1.76–2.67) for clinical examination data, and 3.34 (1.01–11.11) for administrative databases; adjusted ORs were 1.75 (1.34–2.30), 1.59 (1.22–1.96), and 2.47 (0.97–6.33), respectively. In conclusion, VI and depression are prevalent morbidities and should be actively sought when either is identified, especially in older adults.

Aim: To investigate vascular changes of myopic choroidal neovascularization (mCNV) after ranibizumab treatment using optical coherence tomography-angiography (OCTA). Methods: Consecutive subjects with a diagnosis of mCNV were included. Patients underwent intravitreal injection of ranibizumab treatment with a 6-month follow-up. All patients underwent a complete ophthalmological examination and OCTA evaluation. The 3 × 3 OCTA en face images were analyzed for the absence/presence of mCNV, CNV area, and CNV network morphology. In particular, the morphology of the mCNV was analyzed in order to detect the presence/absence of feeder vessels. Results: Eleven subjects were evaluated. At baseline, the mCNV was identified in all cases on OCTA. At 6 months, the mean mCNV area was not statically significantly reduced in comparison with baseline values (p > 0.05), while the morphologic analysis revealed a complete disappearance of the feeder vessel in 6 eyes. The subgroup analysis of these latter showed that the CNV area was significantly reduced, visual acuity had improved, and only one intravitreal injection was administrated over the entire follow-up period. Conclusions: OCTA allowed the detection of qualitative and quantitative vascular changes in mCNV. The disappearance of the feeder vessel was associated with better anatomical as well as functional outcomes at the last follow-up visit.

BackgroundDiabetic retinopathy (DR) is a microvascular complication of diabetes with a heavy impact on the life-quality of subjects and with a dramatic burden for health and economic systems on a global scale.Although the pathogenesis of DR is largely unknown, several preclinical data have pointed out to a main role of Muller glia, a cell type which spans across the retina layers providing nourishment and support for Retina Ganglion Cells (RGCs), in sensing glycemia and in acquiring a proinflammatory polarization in response to this insult.ResultsBy using a validated experimental model of DR in vitro, the rMC1 cells challenged with high glucose, we uncovered the induction of an early (within minutes) and atypical NF-kB signalling pathway regulated by a CamKII-proteasome axis. Phosphorylation of proteasome subunit Rpt6 (at serine 120) by CamKII stimulated the accelerated turnover of IkBα (i.e., the natural inhibitor of p65-50 transcription factor), regardless of the phosphorylation at serine 32 which labels canonical NF-kB signalling. This event allowed the p65-p50 heterodimer to migrate into the nucleus and to induce the selective transcription of IL-8, Il-1β and MCP-1. Pharmacological inhibition of CamKII or proteasome stopped this proinflammatory program, whereas introduction of a Rpt6 phospho-dead mutant (Rpt6-S120A) stimulated a paradoxical effect on NF-kB probably through the activation of a compensatory mechanism which may involve phosphorylation of 20S α4 subunit.ConclusionsThis study introduces a novel pathway of MG activation by high glucose and casts some light on the biological relevance of proteasome post-translational modifications in modulating pathways regulated through targeted proteolysis.

IntroductionDiabetic Macular Edema (DME) is an important complication of Diabetic Retinopathy (DR). Intravitreal steroids in slow-release systems represent a safe and effective therapeutic option for the management of DME, capable of improving patients’ quality of life by reducing the number of injections thus increasing the therapeutic adherence and the effectiveness of the treatment. This study aims to determine the economic impact of DME and the consequences, in terms of both expenditure and organizational impact, associated with a greater use of the intravitreal dexamethasone implant.MethodsThe analysis entailed the comparison between two scenarios: a first scenario based on the current use of therapeutic alternatives available in the Italian healthcare setting (as is) and an alternative scenario based on the assumption of an increased use of intravitreal dexamethasone implant (to be). The results of the analysis are expressed in terms of resource absorption associated with the two scenarios as well as in terms of the cost differential given by their comparison.ResultsDespite an increase in expenditure in terms of acquisition costs of pharmacological alternatives (EUR 898,362) and interventions provided (EUR 22,093,160), the greater use of prolonged-release dexamethasone allows for significant savings in terms of healthcare professionals’ time, follow-up and productivity losses incurred by patient/caregiver. These reductions in healthcare costs resulted in a saving of EUR 1,987,678 over a 5-year period. Such a reduction would allow, considering a total annual management cost of EUR 6,115 for the intravitreal dexamethasone, to treat 325 more patients at the same cost of the as is scenario based on the current rate of use of dexamethasone.ConclusionsIn a context characterized by the need to increase the allocative efficiency of economic resources, the recourse to therapeutic alternatives, such as prolonged release dexamethasone, allowing the reduction of costs for the management of a given pathology is crucial to generate more value for patients and the entire society.

Background Diabetic retinopathy (DR) is a microvascular complication of diabetes with a heavy impact on the quality of life of subjects and with a dramatic burden for health and economic systems on a global scale. Although the pathogenesis of DR is largely unknown, several preclinical data have pointed out to a main role of Muller glia (MG), a cell type which spans across the retina layers providing nourishment and support for Retina Ganglion Cells (RGCs), in sensing hyper-glycemia and in acquiring a pro-inflammatory polarization in response to this insult. Results By using a validated experimental model of DR in vitro, rMC1 cells challenged with high glucose, we uncovered the induction of an early (within minutes) and atypical Nuclear Factor-kB (NF-kB) signalling pathway regulated by a calcium-dependent calmodulin kinase II (CamKII)-proteasome axis. Phosphorylation of proteasome subunit Rpt6 (at Serine 120) by CamKII stimulated the accelerated turnover of IkBα (i.e., the natural inhibitor of p65-50 transcription factor), regardless of the phosphorylation at Serine 32 which labels canonical NF-kB signalling. This event allowed the p65-p50 heterodimer to migrate into the nucleus and to induce transcription of IL-8, Il-1β and MCP-1. Pharmacological inhibition of CamKII as well as proteasome inhibition stopped this pro-inflammatory program, whereas introduction of a Rpt6 phospho-dead mutant (Rpt6-S120A) stimulated a paradoxical effect on NF-kB probably through the activation of a compensatory mechanism which may involve phosphorylation of 20S α4 subunit. Conclusions This study introduces a novel pathway of MG activation by high glucose and casts some light on the biological relevance of proteasome post-translational modifications in modulating pathways regulated through targeted proteolysis.

Inherited retinal degeneration (IRD) represents a clinically variable and genetically heterogeneous group of disorders characterized by photoreceptor dysfunction. These diseases typically present with progressive severe vision loss and variable onset, ranging from birth to adulthood. Genomic sequencing has allowed to identify novel IRD-related genes, most of which encode proteins contributing to photoreceptor-cilia biogenesis and/or function. Despite these insights, knowledge gaps hamper a molecular diagnosis in one-third of IRD cases. By exome sequencing in a cohort of molecularly unsolved individuals with IRD, we identified a homozygous splice site variant affecting the transcript processing of TUB, encoding the first member of the Tubby family of bipartite transcription factors, in a sporadic case with retinal dystrophy. A truncating homozygous variant in this gene had previously been reported in a single family with three subjects sharing retinal dystrophy and obesity. The clinical assessment of the present patient documented a slightly increased body mass index and no changes in metabolic markers of obesity, but confirmed the occurrence of retinal detachment. In vitro studies using patient-derived fibroblasts showed the accelerated degradation of the encoded protein and aberrant cilium morphology and biogenesis. These findings definitely link impaired TUB function to retinal dystrophy and provide new data on the clinical characterization of this ultra-rare retinal ciliopathy.

To study the outer retina morpho-functional characteristics and the choriocapillaris (CC) features in type 1 diabetic (T1D) patients, with and without signs of diabetic retinopathy (NPDR and NoDR). Twenty-five NPDR and 18 NoDR eyes were imaged by Optical Coherence Tomography Angiography. Ellipsoid zone (EZ) “normalized” reflectivity and CC perfusion density parameters, as flow deficits number (FDn), flow deficit average area (FDa) and flow deficit percentage (FD%), were analysed. Multifocal electroretinogram (mfERG) response amplitude densities (RADs) were measured. Mean EZ “normalized” reflectivity, CC FDn and FD% values, were similar (p > 0.05) in both groups, FDa was significant greater (p > 0.05) in NPDR compared with NoDR eyes. MfERG-RADs were similar in both groups. NPDR eyes showed a significant (p

Introduction Our aim was to evaluate the effects of 36 months of treatment with citicoline and vitamin B12 eye drops on macular function in patients with type 1 diabetes (DM1) with mild signs of non-proliferative diabetic retinopathy (NPDR). Methods A prospective, randomized, interventional, monocentric, double-masked study was conducted. Twenty patients with DM1 were enrolled and randomly divided into two groups: the DC group (10 patients; mean age ± standard deviation 46.86 ± 8.78 years) in which one eye of each patient was treated with citicoline and vitamin B12 eye drops (OMK2®, Omikron Italia srl, Italy, one drop thrice daily) for a period of 36 months; the DP group (10 patients; mean age ± standard deviation 47.89 ± 7.74 years) in which one eye of each patient was treated with placebo (eye drops containing hypromellose 0.3%, one drop thrice daily) for a period of 36 months. A total of 18 eyes (10 from the DP and 8 from the DC group, respectively) completed the study. In both groups, multifocal electroretinogram (mfERG) recordings were assessed at baseline and after 36 months. In mfERG analysis, the N1–P1 response amplitude density (RAD) evaluated in the 0–2.5° (ring 1), in the 2.5–5° (ring 2), in the 5–10° (ring 3), and in the 0–10° (ring 1 + ring 2 + ring 3) were considered. Results With respect to baseline, after 36 months of follow-up, the mfERG RADs recorded in R1, R2, R3, and R1 + R2 + R3 were significantly increased (i.e., R1 + R2 + R3 RAD from 21.552 ± 2.522 nV/degree2 at baseline to 26.912 ± 2.850 nV/degree2 at 36 months) in DC eyes, whereas in DP eyes they were significantly reduced (i.e., R1 + R2 + R3 RAD from 21.033 ± 3.574 nV/degree2 at baseline to 16.151 ± 3.571 nV/degree2 at 36 months). Conclusions This study indicates that patients with NPDR treated with citicoline and vitamin B12 eye drops for a 36-month period achieved an improvement of the macular bioelectrical responses detectable by mfERG recordings. By contrast, during the same period of follow-up, patients with NPDR treated with placebo showed a worsening of the macular function.

Purpose: To report the morphological and clinical features of a case of retinitis pigmentosa with large choroidal excavation. Methods: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity assessment, anterior segment and dilated fundus examination and spectral-domain optical coherence tomography. Results: A 41-year-old woman affected by retinitis pigmentosa with genetic confirmation with mutation in RDH12 gene had a best-corrected visual acuity of 20/50 in both eyes. Dilated fundus examination revealed waxy pallor of the optic disc, diffuse narrowing of the retinal arterioles and a generalized retinal pigment epithelium mottling with bony spicule associated with diffuse retinal atrophy. At the posterior pole, an extended bilateral chorioretinal atrophy was evident with a partial sparing of the macular area. On spectral-domain optical coherence tomography, a bilateral large choroidal excavation could be clearly detected and it was associated with a diffuse retinal thinning at the posterior pole and a partial sparing of the fovea. Conclusion: Large choroidal excavation has been rarely reported. Although the pathogenetic mechanisms leading to the formation of large choroidal excavation are still a matter of debate, a combination of primary degenerative-inflammatory factors could be retained responsible for the large choroidal excavation development.

Purpose: To evaluate the agreement between fluorescein angiography and structural optical coherence tomography in diagnosing and monitoring the activity of myopic choroidal neovascularization and to provide a comparative analysis with optical coherence tomography angiography. Methods: Thirteen patients with active myopic choroidal neovascularization were prospectively enrolled. At the baseline, 2-month, and 6-month visits, each patient underwent a complete ophthalmological examination, including best-corrected visual acuity assessment, fundus examination, fluorescein angiography, and optical coherence tomography with structural and angiographic assessment. Sensitivity and specificity for all optical coherence tomography parameters were evaluated taking fluorescein angiography as the reference examination. Results: At the baseline, fluorescein angiography confirmed myopic choroidal neovascularization leakage in all patients. Structural optical coherence tomography demonstrated intraretinal or subretinal fluid in 61% of cases, fuzzy borders and absence of external limiting membrane visibility in 84% of cases, and subretinal hyperreflective exudation in 53% of cases. Sensitivity to the presence of retinal fluid and subretinal hyperreflective exudation was lower than sensitivity to fuzzy borders and external limiting membrane visibility, which reached 84%. During ranibizumab therapy, external limiting membrane visibility showed a higher sensitivity (100%) compared with fuzzy borders and subretinal hyperreflective exudation (66.6%) while displaying an equal specificity of 100%. At baseline and final visit, sensitivity increased to 100% when all structural optical coherence tomography parameters were pooled. Optical coherence tomography angiography detected myopic choroidal neovascularization at baseline, 2-month, and 6-month visits in 92%, 76%, and 76% of cases, respectively. Conclusion: The study confirms that the new indicators of myopic choroidal neovascularization activity are more reliable than the presence or absence of retinal fluid. Optical coherence tomography angiography identified myopic choroidal neovascularization in most patients in the diagnostic phase and during treatment monitoring and could be considered as an alternative to fluorescein angiography in selected patients.

Background To evaluate the effects of Macuprev® supplementation on macular function and structure in intermediate age-related macular degeneration (AMD) along 6 months of follow-up. Methods In this double-blind, monocentric, randomized, and prospective study, 30 patients with intermediate AMD were enrolled and randomly divided into two age-similar groups: 15 patients (AMD-M group; mean age 68.50 ± 8.79 years) received 6-month oral daily supplementation with Macuprev® (Farmaplus Italia s.r.l., Italy, two tablets/day on an empty stomach, before meals; contained in total lutein 20 mg, zeaxanthin 4 mg, N-acetylcysteine 140 mg, bromelain 2500GDU 80 mg, vitamin D3 800 IU, vitamin B12 18 mg, alpha-lipoic acid 140 mg, rutin 157 mg, vitamin C 160 mg, zinc oxide 16 mg, Vaccinium myrtillus 36% anthocyanosides 90 mg, Ganoderma lucidum 600 mg) and 15 patients (AMD-P group; mean age 70.14 ± 9.87) received two tablets of placebo daily on an empty stomach, before meals. A total of 28 eyes, 14 from each AMD group, completed the study. Multifocal electroretinogram (mfERG) and spectral domain-optical coherence tomography (SD-OCT) were assessed at baseline and after 6 months. Results At 6-month follow-up, AMD-M eyes showed a significant increase of mfERG response amplitude density (RAD) recorded from the central macular areas (ring 1, 0–2.5°; ring 2, 2.5–5°), whereas non-significant changes of retinal and choroidal SD-OCT parameters were found when values were compared to baseline. Non-significant correlations between functional and structural changes were found. In AMD-P eyes, non-significant differences for each mfERG and SD-OCT parameters were observed at 6 months. Conclusions In intermediate AMD, Macuprev® supplementation increases the function of the macular pre-ganglionic elements, with no associated retinal and choroidal ultra-structural changes. Trial Registration ClinicalTrials.gov identifier, NCT03919019. Funding Research for this study was financially supported by the Italian Ministry of Health and Fondazione Roma. Article processing charges were funded by Farmaplus Italia s.r.l., Italy.

To describe early and late morphological and functional changes in subjects receiving photodynamic therapy (PDT) for chronic central serous chorioretinopathy.Patients with chronic central serous chorioretinopathy were prospectively enrolled and received standard PDT. At the baseline examination, each subject underwent complete ophthalmological examination, including best-corrected visual acuity (BCVA) assessment, fluorescein angiography and indocyanine green angiography, spectral domain optical coherence tomography, and microperimetry. Spectral domain optical coherence tomography, microperimetry, and BCVA assessment were repeated in multiple sections over 7 days after PDT and at 1-, 3-, and 12-month intervals. Main outcome measures were: identification of early changes (1-week examination) in BCVA, retinal sensitivity, and spectral domain optical coherence tomography parameters and their influence on outcomes at the 1-year follow-up.Three main patterns of early response to PDT were identified during the 1-week examination. The neurosensory retinal detachment most frequently decreased rapidly (12/19 pts), with complete resolution in 50% of cases. An increase in neurosensory retinal detachment height was registered in 16% (3/19) of cases, whereas in 21% (4/19), a large fluctuation in neurosensory retinal detachment was encountered. Best-corrected visual acuity declined significantly in 5/12 patients in the first group and was stable or improved in the remaining cases. Overall, retinal sensitivity diminished in 16/19 subjects, with a mean worsening of 2.56 dB (P = 0.0002). At the 12-month examination, final mean BCVA improved by 14.4 letters (P = 0.001) and a similar progressive recovery in the retinal sensitivity was observed (+2.69 dB, P = 0.0039). The neurosensory retinal detachment completely resolved in 18/19 (95%) cases, with a parallel significant reduction in central foveal choroidal thickness (P0.0001).Three patterns of early response to standard PDT can be identified. Although an early and abrupt reduction in BCVA and retinal sensitivity after treatment is possible, this does not compromise a final improvement in visual functions.

Glutathione transferases (GSTs) play an important role in retinal pathophysiology. Within this family, the GSTP isoform is known as an endogenous regulator of cell survival and proliferation pathways and of cellular responses to oxidative stress. In the present study we silenced GSTP in R28 cells, a retinal precursor cell line with markers of both glial and neuronal origin, and obtained stable clones which were viable and, unexpectedly, characterized by a more neuronal phenotype. The degree of neuronal differentiation was inversely correlated with GSTP residual expression levels. The clone with the lowest expression of GSTP showed metabolic reprogramming, a more favorable redox status and, despite its neuronal phenotype, a sensitivity to glutamate and 4-hydroxynonenal toxicity comparable to that of control cells. Altogether, our evidence shows that near full depletion of GSTP in retinal precursor cells, triggers neuronal differentiation and prosurvival metabolic changes.

Purpose: To investigate the progression of diabetic microaneurysms (MAs) according to the spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) characteristics and to evaluate their influence on the retinal extracellular fluid accumulation at 1 year follow-up in patients with nonproliferative diabetic retinopathy (NPDR). Design: Prospective, observational case series. Methods: Fourteen patients with NPDR underwent SD-OCT and OCTA at the baseline and at 1 year follow-up. For all the selected MAs the visibility, the changes of internal reflectivity, graded as hyporeflective, moderate, or hyperreflective, and the extracellular fluid accumulation surrounding each MA on SD-OCT at 1 year were evaluated. The changes in terms of visualization at the level either of superficial (SCP) or deep (DCP) capillary plexus and the presence of flow on the corresponding OCTA scan at 1 year were evaluated. Results: Of 127 MAs selected at the baseline, 89 (70%) were still visible on SD-OCT at 1 year. The reflectivity pattern at baseline was strongly associated with extracellular fluid accumulation at 1 year, with 18% of hyporeflective vs 66% of hyperreflective MAs developing extracellular fluid (P =.004). Among OCTA findings, the presence of flow (P =.001), the visibility (P

Importance Given that depression is treatable and some ocular diseases that cause visual loss are reversible, early identification and treatment of patients with visual impairment who are most at risk of depression may have an important influence on the well-being of these patients. Objective To conduct a meta-analysis on the prevalence of depression in patients with visual impairment who regularly visit eye clinics and low vision rehabilitation services. Data Sources MEDLINE (inception to June 7, 2020) and Embase (inception to June 7, 2020) were searched. Study Selection Studies that obtained data on the association between acquired visual impairment and depression among individuals aged 18 years or older were identified and included in this review. Exclusion criteria comprised inherited or congenital eye diseases, review studies, unpublished articles, abstracts, theses, dissertations, and book chapters. Four independent reviewers analyzed the results of the search and performed the selection and data extraction to ensure accuracy. Data Extraction and Synthesis Meta-analyses of prevalence were conducted using random-intercept logistic regression models. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main Outcomes and Measures Proportion of depression. Results A total of 27 studies were included in this review, and all but 2 included patients older than 65 years. Among 6992 total patients (mean [SD] age, 76 [13.9] years; 4195 women [60%]) with visual impairment, in 1687 patients with depression, the median proportion of depression was 0.30 (range, 0.03-0.54). The random-effects pooled estimate was 0.25 (95% CI, 0.19-0.33) with high heterogeneity (95% predictive interval, 0.05-0.70). No patient characteristic, measured at the study level, influenced the prevalence of depression, except for the inclusion of patients with cognitive impairment (0.33; 95% CI, 0.28-0.38 in 14 studies vs 0.18; 95% CI, 0.11-0.30 in 13 studies that excluded this with major comorbidities;P = .008). The prevalence of depression was high both in clinic-based studies (in 6 studies, 0.34; 95% CI, 0.23-0.47) and in rehabilitation services (in 18 studies, 0.25; 95% CI, 0.18-0.33 vs other settings in 3 studies, 0.15; 95% CI, 0.05-0.38;P = .17), and did not vary by visual impairment severity of mild (in 8 studies, 0.24; 95% CI, 0.14-0.38), moderate (in 10 studies, 0.29; 95% CI, 0.21-0.39), and severe (in 5 studies, 0.29; 95% CI, 0.12-0.56;P = .51). Conclusions and Relevance The results of this meta-analysis suggest that depression in patients with visual impairment is a common problem that should be recognized and addressed by the health care professionals treating these patients.

Retina and optic nerve are sites of extra-cerebral manifestations of Alzheimer’s Disease (AD). Amyloid-β (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau protein are detected in eyes from AD patients and transgenic animals in correlation with inflammation, reduction of synapses, visual deficits, loss of retinal cells and nerve fiber. However, neither the pathological relevance of other post-translational tau modifications—such as truncation with generation of toxic fragments—nor the potential neuroprotective action induced by their in vivo clearance have been investigated in the context of AD retinal degeneration. We have recently developed a monoclonal tau antibody (12A12mAb) which selectively targets the neurotoxic 20–22 kDa NH2-derived peptide generated from pathological truncation at the N-terminal domain of tau without cross-reacting with its full-length normal protein. Previous studies have shown that 12A12mAb, when intravenously (i.v.)-injected into 6-month-old Tg2576 animals, markedly improves their AD-like, behavioural and neuropathological syndrome. By taking advantage of this well-established tau-directed immunization regimen, we found that 12A12mAb administration also exerts a beneficial action on biochemical, mor- phological and metabolic parameters (i.e. APP/Aβ processing, tau hyperphosphorylation, neuroinflammation, syn- aptic proteins, microtubule stability, mitochondria-based energy production, neuronal death) associated with ocular injury in the AD phenotype. These findings prospect translational implications in the AD field by: (1) showing for the first time that cleavage of tau takes part in several pathological changes occurring in vivo in affected retinas and vitre- ous bodies and that its deleterious effects are successfully antagonized by administration of the specific 12A12mAb; (2) shedding further insights on the tight connections between neurosensory retina and brain, in particular following tau-based immunotherapy. In our view, the parallel response we detected in this preclinical animal model, both in the eye and in the hippocampus, following i.v. 12A12mAb injection opens novel diagnostic and therapeutic avenues for the clinical management of cerebral and extracerebral AD signs in human beings.

Objectives To investigate the real-life experience of patients affected by neovascular age-related macular degeneration (nAMD), in the healthcare pathway for the management of the disease, using a "patient journey" and narrative method approach. Methods The patient journey of subjects affected by nAMD was designed using a process-mapping methodology involving a team from 11 Italian centres. Subsequently, narratives were collected from nAMD patients and family members. The interviews were analyzed using the narrative medicine methodology. Results Eleven specialized retina centres across Italy were involved and 205 narratives collected. In 29% of cases, patients underestimated their symptoms or attributed them to non-pathological causes, thus delaying the specialist consultation. The delay in accessing to care was due to a lack of awareness of this disease (50% of the participants didn't know what nAMD is) and to critical issues faced at first visit (long waiting lists, failed diagnosis, underestimation of the problem). Despite anti-VEGF therapies were perceived as effective in improving or stabilizing vision in 91% of narratives collected, 77% of patients still reduced or ceased daily activities such as reading and driving. Within the pathway of care there was not a multidisciplinary approach, and the patients were treated just by the ophthalmologist. Conclusions nAMD may significantly affect the quality of life of affected patients, both from a functional and psychological point of view. The narrative medicine approach highlights some critical points in the healthcare journey of nAMD patients and represents a useful background in implementing patient management algorithms and pathways of care.

Purpose: To evaluate the superficial (SCP) and deep retinal capillary plexus (DCP) by mean of optical coherence tomography angiography (OCTA) in treatment-naïve patients affected by rheumatoid arthritis (RA). Methods: Between March 2019 and January 2020, patients with recent diagnosis of “definite RA” based on 2010 Rheumatoid Arthritis Classification Criteria were included in a Prospective, observational single center case-control study carried out at G.B. Bietti Foundation. Data were compared with those of 16 healthy age- and sex-matched subjects. Values of the vessel density (VD) of SCP and DCP, central foveal thickness (CFT), foveal avascular zone (FAZ) were collected by mean of OCTA. Main outcome measure was the VD alteration of SCP and DCP in treatment-naïve RA-patients. Results: No difference in age, sex-distribution, best-corrected visual acuity, CFT was registered between the two groups. OCTA data analysis showed in RA-patients a statistically significant reduction in the VD in the mean global area, inner ring, especially in the superior quadrant of the SCP. A trend of VD reduction was also registered in temporal, nasal, and inferior quadrants, respectively, although it did not reach a statistically significant value. Assessment of VD of DCP and FAZ area did not evidence any difference among the groups. Conclusions: OCTA allows to highlight the vascular remodeling of the retinal microcirculation in RA-patients, even in early stages of the disease, demonstrating a reduction of VD. Outcomes of the current investigation can provide new insight in the pathogenetic mechanism of RA and extend the potential applications of this diagnostic tool.

Central serous chorioretinopathy represents the fourth most frequent retinal disorder, occurring especially in young age. Central serous chorioretinopathy is mainly characterized by macular serous retinal detachment and although the clinical course moves frequently toward a spontaneous resolution, the subretinal fluid may persist for a long time, thus evolving to the chronic form, and leading to a potential damage of the retinal pigment epithelium and to photoreceptors. The photodynamic therapy with verteporfin plays an important role in the armamentarium among the many therapeutic options employed in this complex retinal disorder. In this review, the authors aim to summarize data of efficacy and safety of PDT focusing especially on mechanisms of action of the PDT and providing comparative outcomes with the alternative therapeutic approaches, including especially the subthreshold laser treatment.

Purpose: To describe two cases of Cobb’s tufts in apparently healthy subjects. Methods: Observational case series. Results: Two patients reporting sudden vision loss, with subsequent complete recovery, underwent a complete ophthalmological examination, including iris fluorescein angiography. Both patients took an “eye-selfie” using their smartphone to provide evidence of the iris bleeding. Iris fluorescein angiography confirmed the presence of iris neovascular tufts at the pupillary margin. Conclusion: Diagnosis of Cobb’s tufts can frequently be challenging. The two patients’ astute action in taking photographs of the eye enabled the condition to be promptly identified.

Aims To evaluate the timing and spectral-domain optical coherence tomography (SD-OCT) features of diabetic macular oedema (DME) recurrence according to baseline OCT patterns in patients treated with dexamethasone implant (DEX-I). Methods This is a retrospective observational study (72 eyes/65 patients). Best-corrected visual acuity, timing of DME recurrence, and SD-OCT pattern [intraretinal cysts (IRC), IRC plus subretinal fluid (mixed), external limiting membrane (ELM), ellipsoid (IS/OS) layer integrity] were assessed at baseline and monthly until first DME recurrence. Results Forty-two (58.3%) and 30 (41.6%) DME eyes had an IRC and mixed DME pattern at baseline, respectively. Twenty-four out of thirty mixed eyes (80%) relapsed without subretinal fluid. At baseline, mixed eyes showed similar changes in ELM and IS/OS (60 and 76.6% of eyes, respectively) versus IRC eyes (42.8 and 80.9% of eyes). After DME recurrence, more mixed eyes at baseline showed ELM and IS/OS changes (63.3 and 86.6%) than IRC eyes (50 and 76.2%). 33.3% of mixed eyes had DME recurrence at ≥ 6 months from first DEX-I implant versus 19% of IRC eyes. Conclusions Mixed DME eyes were treated with DEX-I relapse later and more frequently without subretinal fluid than IRC eyes. SD-OCT characteristics of different DME patterns at baseline can predict morphological features and timing of DME recurrence.

Purpose: To report clinical outcomes of two different timings of intravitreal dexamethasone (DEX) implant administration for prevention of diabetic macular oedema (DME) worsening following cataract surgery. Methods: This multicentre, retrospective study included patients with DME who received an intravitreal DEX implant 1month before cataract surgery, ‘precataract DEX’ group, or at the time of cataract surgery, ‘concomitant treatments’ group. Inclusion criteria were a follow-up ≥3months and ophthalmological examination with optical coherence tomography (OCT) imaging at baseline (cataract surgery) and throughout follow-up. Anatomical improvement was considered to be a decrease in OCT central subfield (CSF) thickness ≥20% compared to baseline. The primary outcomes were anatomical and functional results at 3months. Results: Two hundred twenty-one patients were included: 136 in the ‘precataract DEX’ group and 85 in the ‘concomitant treatments’ group. At 3months, a reduction of CSF thickness≥20% was found in 7.3% of eyes in the ‘precataract DEX group’ and in 83.7% of eyes in the ‘concomitant treatments’ group (p&nbsp