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Purpose Retinal neurodegeneration and inflammation are considered early events in diabetic retinopathy( DR). Herein are described changes, in retinal glial and neuronal cells, with spectral domain( SD- OCT) in patients with non proliferative DR. Methods 130 subjects were evaluated:88 diabetics with DR and 42 normals.All subjects underwent full ophthalmologic examination and SD- OCT. After automatic retinal segmentation in 5 layers, the thickness of each layer was calculated and compared. Intraretinal hyperreflective spots( HRS) were evaluated on linear scans. Results A significant increase in inner nuclear ( INL) and outer plexiform(p < 0.01) and decrease in retinal nerve fiber layer ( RNFL) thickness (p < 0.01) was found in DR eyes (without DME) vs controls. HRS number was significantly higher in diabetics with DR with or without DME vs controls,(p < 0.05). HRS number increased with progressing DR. Conclusion Selective thinning of inner retina in the macula, suggesting an early neuronal loss(accompanied by Muller cells activation with increased INL thickness) in DR is reported. HRS increase and migration to outer retina, may represent a surrogate of microglial activation. SD- OCT may be useful in detecting intraretinal changes in DR. [ABSTRACT FROM AUTHOR]

Globally age-related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers. The incidence and prevalence of GA varies across different geographic regions, with the highest rates in those of European ancestry. Although heterogeneity in definitions of GA and reporting strategy can explain some of the discrepancies, the data overall are consistent in showing a lower prevalence in other ethnicities such as those of Asian heritage. This is at present unexplained but thought to be due to the existence of protective factors such as differences in eye pigmentation, diet, environmental exposures and genetic variability. This review covers key aspects of the prevalence and incidence of the ocular precursor features of GA (large drusen, pigmentary abnormalities and reticular pseudo-drusen), the late stage of GA and factors that have been known to be associated with modifying risk including systemic, demographic, environment, genetic and ocular. Understanding the global epidemiology scenario is crucial for the prevention of and management of patients with GA., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To correlate metamorphopsia provided by M-CHARTS and ectopic inner foveal layers (EIFL) or 'central bouquet' abnormality (CBA) in patients with advanced stages of epiretinal membrane (ERM) following the novel Optical Coherence Tomography (OCT)-based grading scheme., Methods: In 60 eyes of 57 patients affected by ERM (stages 3 and 4), the degree of metamorphopsia using the M-CHARTS was evaluated (M-SCORE) and correlated with EIFL, CBA and central foveal thickness (CFT) as measured on OCT scans., Results: A total of 37 and 23 eyes were diagnosed having ERM stages 3 and 4, respectively. Mean vertical and horizontal M-SCORE (M-V and M-H) were 0.64 ± 0.43 and 0.58 ± 0.37 standard deviations, respectively. Mean M-SCORE exhibited a statistically significant correlation with EIFL and CFT (both p < 0.0001), but not with CBA (p = 0.84). Analysing the direction of metamorphopsia separately, M-H and M-V were significantly correlated with EIFL (both p < 0.0001), but not with CBA thickness (p = 0.70 and 0.33 respectively). Ectopic inner foveal layers (EIFL) was significantly influenced by the presence of CBA (CBA present, 158.29 ± 63.53 micron; CBA absent, 107.05 ± 94.13 micron, p = 0.04). No significant differences were found for both M-V and M-H with respect to the presence of CBA., Conclusions: Based on the novel OCT-based grading scheme for ERMs, our results demonstrate that EIFL, but not CBA, might be considered a good indicator for metamorphopsia in patients with advanced ERMs., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate choriocapillaris (CC) perfusion, by evaluating flow voids (FV), in eyes with intermediate age-related macular degeneration (iAMD) using swept-source optical coherence tomography angiography (SS-OCT-A)., Methods: Patients with bilateral or unilateral iAMD and normal controls underwent SS-OCT and OCT-A examination. Choriocapillaris (CC) FVs were quantitatively assessed on OCT-A images using matlab (version 2017b; MathWorks, Natick, MA, USA), after a preprocessing aimed at compensating for CC attenuation artefacts. Three different thresholds [1 standard deviation (SD), 1.25 SD and 1.5 SD] were applied. Final FV percentage (FV%) was calculated as the ratio between area with absent flow and total scanned area., Results: Of 41 patients with iAMD and 16 normal subjects enrolled in the study, 39 eyes (39 patients) with iAMD and all 16 normal eyes (16 control subjects) were included in the final analysis. Mean FV% (1 SD) was 13.45 ± 0.66 in controls, 14.19 ± 1.23 in bilateral iAMD and 14.21 ± 0.99 in unilateral iAMD (p = 0.03, for difference between controls and bilateral iAMD). Mean FV% (1.25 SD) was 6.55 ± 0.65 in controls, 7.33 ± 1.4 in bilateral iAMD and 7.06 ± 1.4 in unilateral iAMD (p = 0.048, for difference between controls and bilateral iAMD). Mean FV% (1.5 SD) was 2.71 ± 0.82 in controls, 2.55 ± 1.12 in bilateral iAMD and 3.25 ± 1.17 in unilateral iAMD (p = 0.038, for difference between bilateral and unilateral iAMD)., Conclusion: A significantly higher FV% was found in patients with iAMD versus controls. A higher trend in FV% was found in unilateral iAMD (with neovascular AMD in the fellow eye) versus bilateral iAMD, when applying the lowest threshold. Further, larger and longitudinal studies are needed to confirm this data., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Subthreshold micropulse laser (SMPL) has been increasingly used for the treatment of different retinal and choroidal macular disorders. However, the exact mechanisms of action have not yet been clearly defined. Therefore, we aimed to examine the role of SMPL treatment in the modulation of oxidant/antioxidant systems, apoptosis and autophagy in the mice eyes., Methods: A specific laser contact lens for retina was positioned on the cornea of 40 mice (20 young and 20 old) in order to focus the laser on the eye fundus for SMPL treatment. Within 6 months, 20 animals received one treatment only, whereas the others were treated three times. Eye specimens underwent histological analysis and were used for thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) quantification, as well as for the superoxide dismutase 1 (SOD1) and the selenoprotein thioredoxin reductase 1 (TrxR1) expression evaluation. Western blot was performed for nitric oxide synthase (NOS) subtypes detection and to examine changes in apoptotic/autophagy proteins expression., Results: SMPL treatment reduced TBARS and increased GSH and SOD1 in the mice eyes. It also reduced cytochrome c, caspase 3 expression and activity and cleaved caspase 9, and increased Beclin 1, p62 and LC3β. The effects were more relevant in the elderly animals., Conclusion: Our results showed that SMPL therapy restored the oxidant/antioxidant balance within retinal layers and modulated programmed forms of cell death. Further studies may confirm these data and could evaluate their relevance in clinical practice., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate changes of specific retinal imaging biomarkers [intraretinal hyper-reflective retinal spots: HRS ; subfoveal neuroretinal detachment: SND; and increased foveal autofluorescence: IFAF after intravitreal steroid or anti-vascular endothelial growth factor treatment in diabetic macular oedema (DME)] as possible indicators of retinal inflammatory condition., Methods: Retrospective analysis of images and clinical charts of 49 eyes (49 patients) with DME treated with intravitreal dexamethasone (dexamethasone, 23 eyes) or intravitreal ranibizumab (ranibizumab, 26 eyes). All patients had fundus colour photograph, spectral domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF), best-corrected visual acuity (BCVA) and microperimetry recorded before and 1 month after the end of treatment. Central macular thickness (CMT), number of HRS and presence of SND were evaluated by SD OCT. Fundus autofluorescence images were evaluated for area of (IFAF). Retinal sensitivity within 4° and 12° from fovea was quantified by microperimetry. Changes in morphologic and functional parameters were assessed, and correlation was performed by Pearson's correlation., Results: Best-corrected visual acuity and CMT improved in all patients, (p < 0.05, for both groups). Mean number of HRS decreased after both treatments (p < 0.0001). Subfoveal neuroretinal detachment resolved in 85.7% dexamethasone-treated eyes (p = 0.014) and in 50% ranibizumab-treated eyes (p = 0.025). Mean IFAF area decreased in both groups, (p < 0.0001, for both). A significantly higher decrease in CMT was observed in dexamethasone- versus ranibizumab-treated eyes, (p = 0.032). In dexamethasone group, higher number of HRS at baseline and larger IFAF were correlated with higher increase in retinal sensitivity; eyes with SND at baseline had major decrease in CMT versus those without SND, (p = 0.003)., Conclusion: Higher number of HRS, larger area of IFAF and presence of SND may indicate a prevalent inflammatory condition in DME with specific response to targeted treatment., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Retinal glia cells (RGC) activation and release of inflammatory cytokines have been associated with development of diabetic retinopathy (DR). In this study, we evaluated by protein array the presence of aqueous humour (AH) cytokines secreted by RGC in patients with diabetes without DR and with mild DR., Methods: This is a cross-sectional, case-control study. Thirty-five subjects (diabetics and controls) underwent full ophthalmic examination and AH samples collection before cataract surgery at the Department of Ophthalmology University of Padova. AH samples were analysed for total protein concentration (Bradford method) and RGC-related inflammatory cytokines using glass chip protein arrays., Results: Twelve diabetic patients without DR, 11 diabetic patients with mild DR and 12 non-diabetic controls were included. There was no significant difference in total protein concentration among the 3 groups. Interleukin IL-1β, IL-3, interferon gamma (IFN-ɣ), (IFN-ɣ)-induced protein (IP)-10 and monocyte chemotactic protein (MCP)-2 were significantly increased in diabetics versus controls. IFN-ɣ, IL-1α, IL-3 and MCP-2 were significantly increased in diabetics without DR versus controls, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-ɣ, IL-10, IP-10, regulated and normal T cell expressed and secreted (RANTES), and soluble tumour necrosis factor receptor (sTNF-R)II were significantly increased in diabetics with mild DR versus controls. Macrophage inflammatory protein (MIP-1β), GMCSF, RANTES and sTNF-RII were significantly increased in diabetics with mild DR versus diabetics without DR (p < 0.05 at least for all)., Conclusions: Differences in expression profile of AH cytokines between diabetics, without and with mild DR, and controls have been documented. Retinal neuroinflammatory biomarkers of RGC activation evaluated in AH by protein array analysis could guide in detecting specific phenotypes with potential for personalized management., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To determine the validity of scanning laser ophthalmoscopy in the retromode (RM-SLO) versus other imaging modalities in the diagnosis of diabetic macular oedema (DME)., Methods: Two hundred and sixty-three eyes were examined. Inclusion criteria were any stage of untreated or treated diabetic retinopathy and four imaging modalities of the macula carried out on the same day: time domain optical coherence tomography (OCT), fundus autofluorescence (FAF), RM-SLO and fluorescein angiography (FA). Two masked retinal specialists independently graded all images. Agreement between RM-SLO and OCT, FA and FAF in evaluating the presence and patterns of DME was evaluated by kappa statistics, sensitivity, specificity, observed proportional agreement, and proportional agreement in positive and negative cases., Results: The agreement in evaluating the presence/absence of DME between RM-SLO and OCT, FA and FAF was good: κ = 0.73 (confidence interval; CI, 0.64-0.83), κ = 0.71 (CI, 0.61-0.81) and κ = 0.73 (CI, 0.63-0.83), respectively. The agreement in evaluating cystoid pattern of DME was almost perfect between RM-SLO and OCT, RM-SLO and FA, κ > 0.8; and good between RM-SLO and FAF, κ > 0.7. The agreement in evaluating the presence/absence of subfoveal neuroretinal was almost perfect between RM-SLO and OCT (κ = 0.83; 95% CI, 0.70-0.96). Subfoveal neuroretinal detachment did not show any specific pattern on FA or FAF. Sensitivity and specificity of RM-SLO in evaluating DME was 97.7% and 71.9% versus OCT, 97.4% and 68.1% versus FA and 96.1% and 73.3% versus FAF. Retinal thickness of 233 μm represented the cut-off value to define DME by RM-SLO., Conclusions: The combined use of non-invasive imaging techniques can improve the diagnostic interpretation of different aspects of DME., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)