To evaluate the spontaneous change in size over the time of idiopathic full-thickness macular holes (IFTMHs) using optical coherence tomography (OCT).
This retrospective observational study included ...24 eyes of 24 consecutive patients waiting for IFTMH surgery. On OCT horizontal B-scan passing through the center of the fovea, the minimum linear diameter (MLD), the basal diameter (BD), and the presence of vitreomacular adhesion (VMA) were evaluated. The mean total and daily MLD and BD variations were calculated as both absolute and percentage values.
The MLD and BD size increase was statistically significant (P < 0.0001). The MLD size increase was significantly greater for small (<250 μm) versus both medium (≥250 to ≤400 μm) and large (>400 μm) IFTMHs in all analysis: the total absolute (P = 0.0248), the daily absolute (P = 0.0186), the total percentage (P = 0.0020), and the daily percentage (P = 0.0008) variations. For the BD, the significance between the same groups was achieved only in the daily percentage change (P = 0.0220). The presence of VMA did not influence the amount of MLD and BD increase. The rate of increase was dependent on the size of hole at presentation (MLD: small: 1.67 microns per day; medium: 0.61 microns per day; large: 0.44 microns per day).
Both MLD and BD increase over the time in IFTMHs. There is a significantly greater rate of increase in hole size in smaller holes compared with larger. Therefore, prioritisation for small IFTMH may be justified.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To identify early biomarkers of retinal Müller cell activation in diabetic eyes with or without clinically detectable signs of diabetic retinopathy (DR).
This study was a cross-sectional comparative ...case series. The aqueous humor (AH) of 34 eyes was collected in 12 healthy controls, 11 diabetic patients without DR, and 11 diabetic patients with nonproliferative DR. Full ophthalmic examination and spectral-domain optical coherence tomography were performed in all eyes. Glial fibrillary acidic protein (GFAP), aquaporin 1 (AQP1), and aquaporin 4 (AQP4) were quantified in AH samples as biomarkers of Müller cell activity by ELISA. Statistical analysis was performed with ANOVA followed by Tukey-Kramer post hoc test.
There was no significant difference in the age among the three groups. Mean concentration of GFAP, AQP1, and AQP4 significantly increased in diabetic eyes versus controls (P < 0.05, for each comparison). Glial fibrillary acidic protein and AQP1 showed an approximate 2-fold increase, whereas AQP4 showed an approximate 25-fold increase in diabetics with DR versus controls. In diabetics without DR, AQP4 showed an approximate 6-fold increase versus controls.
Glial fibrillary acidic protein, AQP1, and AQP4-biomarkers of Müller cell activity-are significantly increased in human eyes with diabetes, confirming that Müller cells are precociously affected by diabetes mellitus.
To assess and correlate early modifications in hyperreflective retinal spots (HRS), retinal sensitivity (RS), fixation stability, and best-corrected visual acuity (BCVA) after anti-vascular ...endothelial growth factor treatment in naive center-involving diabetic macular edema.
Cross-sectional comparative case-control series. Twenty diabetic patients underwent 3 consecutive intravitreal anti-vascular endothelial growth factor injections in the study eye (20 fellow eyes served as control), full ophthalmologic examination including spectral domain optical coherence tomography (Retinascan RS-3000; Nidek, Gamagori, Japan), and microperimetry (MP1; Nidek) at baseline (Visit-V1), 1 month after each injection (V2, V3, V4), and at 6 months (V5). Central retinal thickness, inner and outer retinal thickness, number of HRS, BCVA, RS, and bivariate contour ellipse area were evaluated by analysis of variance test with Bonferroni post hoc test. Correlation analyses were performed by Spearman correlation.
In treated eyes, central retinal thickness and inner retinal thickness significantly decreased at V2, V3, V4 versus V1 (P < 0.03 at least for all); the mean number of HRS significantly decreased in both inner and outer retina at all follow-up visits versus V1 (P < 0.008 at least for all); mean RS and bivariate contour ellipse area remained statistically unchanged during the follow-up; BCVA significantly improved at V3, V4, and V5 versus V1 (P = 0.009 at least for all). In fellow eyes, central retinal thickness, HRS, RS, and BCVA did not change at any follow-up. The number of HRS correlated inversely with RS, directly with bivariate contour ellipse area, and not significantly with BCVA.
A significant decrease in HRS in the retina after anti-vascular endothelial growth factor treatment is documented. A decrease in HRS correlates with functional parameters, specifically RS. New parameters may be used for treatment evaluation in center-involving diabetic macular edema.
Purpose. To evaluate the presence of hyperreflective spots (HRS) in diabetic patients without clinically detectable retinopathy (no DR) or with nonproliferative mild to moderate retinopathy (DR) ...without macular edema, and compare the results to controls. Methods. 36 subjects were enrolled: 12 with no DR, 12 with DR, and 12 normal subjects who served as controls. All studied subjects underwent full ophthalmologic examination and spectral domain optical coherence tomography (SD-OCT). SD-OCT images were analyzed to measure and localize HRS. Each image was analyzed by two independent, masked examiners. Results. The number of HRS was significantly higher in both diabetics without and with retinopathy versus controls (P<0.05) and in diabetics with retinopathy versus diabetics without retinopathy (P<0.05). The HRS were mainly located in the inner retina layers (inner limiting membrane, ganglion cell layer, and inner nuclear layer). The intraobserver and interobserver agreement was almost perfect (κ> 0.9). Conclusions. SD-OCT hyperreflective spots are present in diabetic eyes even when clinical retinopathy is undetectable. Their number increases with progressing retinopathy. Initially, HRS are mainly located in the inner retina, where the resident microglia is present. With progressing retinopathy, HRS reach the outer retinal layer. HRS may represent a surrogate of microglial activation in diabetic retina.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: To evaluate the earliest retinal morphological and functional changes in diabetic eyes without or with early signs of diabetic retinopathy (DR). Methods: Twenty-two eyes with no DR (noDR ...group), 22 eyes with mild DR (DR group), and 18 healthy nondiabetic eyes (controls) were enrolled. All eyes were studied by means of spectral domain optical coherence tomography (OCT), OCT angiography (OCTA), and multifocal electroretinogram (mfERG). Results: A significantly higher number of OCT hyperreflective intraretinal foci (HRF) was found in both noDR and DR groups versus controls, but not between DR groups. The OCTA parameters of the superficial vascular plexus (SVP) were significantly reduced in the noDR group both versus controls and DR group (p < 0.05). The OCTA parameters of the intermediate capillary plexus (ICP) were significantly reduced in the DR group versus controls. An increased number of altered hexagons on mfERG was found in the noDR versus the DR group (p = 0.0192). Conclusions: Retinal vascular and functional parameters are differently involved in diabetic eyes; major vascular changes in the SVP and functional alterations of the mfERG are present in diabetic eyes with no clinical microvascular signs of DR, while ICP is mainly involved when early ophthalmoscopic signs of DR are present. The integrated use of mfERG and OCTA provides new significant insights into the pathogenesis of diabetic related retinal disease.
To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND−).
Cross-sectional, ...prospective, comparative case series.
Seventy-two patients (72 eyes: 22 eyes SND+ and 50 eyes SND−) with treatment-naïve, center-involving DME were evaluated. Data gathering included fundus color photographs, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), and microperimetry. The following parameters were evaluated with SD-OCT: central macular thickness (CMT including SND); central retinal thickness (CRT excluding SND); choroidal thickness (CT); nasal and temporal retinal thickness (RT) at 500 μm and 1500 μm from the fovea; the number of hyperreflective retinal spots (HRS) in the central 3000 μm; and the presence of SND and integrity of the external limiting membrane (ELM). Retinal sensitivity (RS) was evaluated within 4 degrees and 12 degrees of the fovea. Correlation among CT, RS, and HRS in patients with and without SND was determined.
CMT (P = .032), temporal RT at 1500 μm (P = .03), mean CT (P = .009), and mean number of HRS (P = .0001) were all higher in SND+ vs SND− eyes. CRT, BCVA, HbA1c, and prevalence of systemic arterial hypertension were not different between the 2 groups. RS within 4 degrees (P = .002) and 12 degrees (P = .015) was lower in SND+ vs SND− eyes. SND correlated significantly with disruption of the ELM (54.55% vs 24%, P = .01) and lower RS. A direct correlation was found between the number of HRS, presence of SND, CT, and RS within 12 degrees in SND− eyes, and an inverse correlation was found between CT and RS within 12degrees in SND+ eyes.
These data may improve characterization of DME in eyes with SND. DME with SND correlates with greater CT, more HRS, disruption of the ELM, and significant macular functional impairment (RS decrease) vs SND−.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
To evaluate hyperreflective retinal spots (HRS), in normal subjects and diabetic patients without and with macular edema (diabetic macular edema, DME), on linear B-scans and corresponding en face ...image of spectral-domain optical coherence tomography.
Retrospective evaluation of images of 54 eyes/subjects (16 normal subjects, 19 diabetic patients without DME, and 19 with DME). On horizontal B-scan spectral-domain optical coherence tomography, passing through the center of the fovea, the following characteristics of HRS were evaluated: location (inner retina or outer retina), size (≤30 or >30 μm), reflectivity (similar to nerve fiber layer or to retinal pigment epithelium-Bruch complex), and presence or absence of back shadowing. On en face spectral-domain optical coherence tomography, the following patterns were evaluated: 1) isolated HRS (not corresponding to any visible lesion); 2) HRS corresponding to a segment of retinal capillary or microaneurysm wall; and 3) HRS corresponding to hard exudate. All gradings were performed twice by two graders in a masked fashion.
Size ≤30 μm, reflectivity similar to nerve fiber layer, and absence of back shadowing were associated with absence of vessels or any other lesion on en face image (P = 0.0001 for all). Size >30 μm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina were all associated with presence of hard exudate on en face imaging (P < 0.0001 for all). Multiple logistic regression analysis showed that HRS present in the inner retina (P < 0.0001), size >30 μm (P = 0.0029), and presence of back shadowing (P < 0.0001) are directly associated with presence of microaneurysms on en face image. Intragrader and intergrader repeatability were excellent for all evaluations.
Hyperreflective retinal spots ≤30 μm, reflectivity similar to nerve fiber layer, and absence of back shadowing may represent activated microglial cells; HRS >30 μm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina may represent hard exudate; HRS >30 μm, presence of back shadowing, and location in the inner retina may represent microaneurysms. These hypotheses may be tested in further studies.
Abstract Aim To describe a decade long telemedicine screening for diabetic retinopathy (DR) in the metropolitan area of Padova (North-East Italy) and to report about prevalence/incidence of DR and ...maculopathy, rate of progression to STDR and optimal screening interval in patients with no DR at first examination. Methods Observational, longitudinal, cohort study. 9347 patients with Type 1 and Type 2 diabetes mellitus (DM) underwent 17,344 fundus exams (three-45° color photos per eye) in two diabetes clinics and were graded in the Reading Centre, by certified personnel.The incidence of STDR, progression of maculopathy and risk factors were evaluated by log Rank test (Kaplan–Meier method). A receiver operating curve was used to determine the optimal screening interval in patients who at the first examination had no DR. Results the overall prevalence of DR was 27.6%:12.5% mild non proliferative (NPDR), 11.3% moderate NPDR, 2.9% severe NPDR and 0.9% proliferative (PDR). The overall prevalence of maculopathy was 5.7%:2.8% mild, 2.2% moderate and 0.7% severe maculopathy.The 10-year incidence of STDR was:0.6% in no DR, 5.5% in mild NPDR and 21.1% in moderate NPDR at first examination.The 10-year incidence of maculopathy was:2.1% mild, 1.7% moderate and 0.2%severe.The incidence of STDR in patients with type 1 and type 2 DM and duration > 10 years was 8.21% and 8.15%;in type 1 DM with duration < 10 years was 5.5% and in type 2 DM and duration < 10 years was 1.91%.In patients with no DR at first screening, the best (sensitivity-specificity) follow-up interval is 2.5 years. Conclusions Screening every 2.5-year in patients without DR at the first examination seems to be adequate. Duration of disease is a relevant risk factor for progression to STDR, however patients with type 1 DM and duration < 10 years have greater incidence of STDR than patients with type 2 DM and similar disease duration. Epidemiologic data from this decade-long screening program in the North East of Italy may serve for implementing a national screening program.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Wilson disease (WD) is a disorder of hepatic copper metabolism leading to copper accumulation in hepatocytes and in extrahepatic organs, as the brain and cornea. The aim of this study was to ...investigate central corneal changes and in particular to assess the parameters of corneal subbasal nerve plexus (SBNP) in patients affected by WD, using corneal confocal microscopy (CCM).
A total of 24 patients affected by WD and 24 healthy control subjects were included in this cross-sectional comparative study. One eye of each subject was examined to quantify different corneal parameters. Mean cell diameter and mean cell density of the epithelium; number of fibers (NF), nerve fiber length density (NFLD), number of branchings (NBr), number of beadings (NBe), and fiber tortuosity (FT) of the SBNP; mean cell density of keratocytes of the anterior, medium, and posterior stroma; and mean cell density, polimegatism, and pleomorphism of the endothelium, and central corneal sensitivity were analyzed.
Wilson disease induced significant alterations in SBNP, and corneal epithelium. The NFLD (P < 0.0001), NF (P = 0.001), NBe (P = 0.025), and NBr (P < 0.0001) were significantly lower, whereas FT (P < 0.0001) was significantly higher in WD subjects compared to controls. Moreover mean epithelial cell diameter (P < 0.0001) and mean epithelial cell density (P < 0.0001) were significantly higher and lower compared to controls, respectively.
The CCM showed significant corneal changes in SBNP, with concomitant corneal epithelium changes in WD, demonstrating the presence of small fiber peripheral neuropathy in these patients. The CCM may contribute to diagnosis and monitoring of the peripheral nervous system involvement in WD.
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