Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration

Background: Early age-related macular degeneration (AMD) has been correlated with different functional alterations, but the exact relationship between fundus lesions and overlying sensitivity is not well known. The aim of this study was to compare fundus-related sensitivity (microperimetry) and fundus autofluorescence (FAF) of the macular area with drusen and pigment abnormalities in early AMD. Methods: 13 consecutive patients with early AMD and visual acuity of 20/20 were studied by means of microperimetry, which automatically analyses macular light differential threshold and fixation patterns. Fundus colour photo and FAF of the macular area were recorded on the same day. Microperimetry was exactly (topographically) superimposed over FAF images. Results: Macular sensitivity significantly decreased over large drusen (11.2 ± 5.6 dB, p<0.0001) and over pigment abnormalities (13.1 ± 3.6 dB, p<0.0001). When both characteristics were present the reduction was greater if compared with its absence (9.6 ± 4.3 versus 15.0 ± 4.5 dB, p<0.0001). Sensitivitity reduction was significant in areas with altered FAF when compared with areas with normal FAF (p<0.0001). Conclusions: Increased FAF in early AMD has a functional correlate exactly quantified by microperimetry. In retinal areas affected by early AMD retinal sensitivity deteriorates, despite good visual acuity. Microperimetry may allow the early detection of functional impairment caused by these lesions. Both microperimetry and FAF may be useful to monitor AMD progression

Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two Different Morphologic and Functional Entities

PURPOSE: To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND). DESIGN: Cross-sectional, prospective, comparative case series. METHODS: Seventy-two patients (72 eyes: 22 eyes SND + and 50 eyes SND) with treatment-naive, 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 mu m and 1500 mu m from the fovea; the number of hyperreflective retinal spots (HRS) in the central 3000 mu m; 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. RESULTS: CMT (P = .032), temporal RT at 1500 mu m (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. CONCLUSIONS: 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

Pegylated interferon-associated retinopathy is frequent in hepatitis C virus patients with hypertension and justifies ophthalmologic screening

Treatment with pegylated interferon alpha (PegIFNα) and ribavirin is still regarded as the standard of care for chronic hepatitis C virus (HCV). Retinopathy has been occasionally described but prospective, longitudinal data are lacking. We investigated the frequency and clinical significance of retinopathy during therapy with PegIFNα and ribavirin in 97 consecutive HCV patients. In all, 54 (55.7%) and 43 (44.3%) patients were treated with PegIFNα 2a and PegIFNα 2b, respectively. Ophthalmologic examination was performed before therapy (baseline), at 3 and 6 months (3T and 6T, respectively) of therapy, and 3 months after the end of therapy (3ET). All patients underwent the baseline and 3T examination, 95.9% and 90.7% of patients underwent 6T and 3ET examination, respectively. Overall, 30.9% of patients developed retinopathy, as defined by the presence of cotton wool spots and/or retinal hemorrhages. Variables significantly associated with retinopathy during treatment were age (P = 0.004), metabolic syndrome (P = 0.05), hypertension (P < 0.0001), cryoglobulinemia (P = 0.05), and preexisting intraocular lesions at baseline (P = 0.01). By multivariate analysis, the only variable independently associated with PegIFNα-associated retinopathy was hypertension (hazard ratio [HR] = 4.99, 95% confidence interval [CI] 2.29-10.89). The frequency of retinopathy was significantly higher in hypertensive patients versus those without hypertension at all timepoints (18.5% versus 5.7% at baseline, P = 0.05; 48.1% versus 15.7% at 3T, P = 0.0009; 68.0% versus 19.1% at 6T, P < 0.0001; 32.0% versus 6.2%, P = 0.0005 at 3ET). In one (1.1%) hypertensive patient, who developed bilateral branch retinal vein occlusion at 6T, the therapy was discontinued. A cost analysis showed that screening for PegIFNα-associated retinopathy was cost-effective as compared with thyroid-stimulating hormone screening. Conclusion: Retinopathy is frequent during treatment with PegIFNα and ribavirin, especially in hypertensive patients, who may develop serious complications. Screening for PegIFNα-associated retinopathy should be recommended for HCV patients with hypertension

Microperimetry and fundus autofluorescence in diabetic macular edema subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

Abstract PURPOSE: The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy Study photocoagulation for clinically significant diabetic macular edema. METHODS: A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months. RESULTS: Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P < 0.0001), and mean central 4 degrees and 12 degrees retinal sensitivity increased in the micropulse diode laser group (P = 0.02 and P = 0.0075) and decreased in the Early Treatment Diabetic Retinopathy Study group (P = 0.2 and P = 0.0026). There was no significant difference in either best-corrected visual acuity or central retinal thickness between the 2 treatment groups (P = 0.48 and P = 0.29), whereas there was a significant difference in 4 degrees and 12 degrees retinal sensitivity (P = 0.04 and P < 0.0001). Fundus autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months. DISCUSSION: Micropulse diode laser seems to be as effective as modified Early Treatment Diabetic Retinopathy Study laser photocoagulation in the treatment of clinically significant diabetic macular edema. Micropulse diode laser treatment does not determine any change on FAF showing (at least) nonclinically visible damage of the retinal pigment epithelium. Microperimetry data encourage the use of a new, less aggressive laser therapeutic approach in the treatment of clinically significant diabetic macular edema

Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema

PurposeTo 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. MethodsRetrospective 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 1month 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 degrees and 12 degrees from fovea was quantified by microperimetry. Changes in morphologic and functional parameters were assessed, and correlation was performed by Pearson's correlation. ResultsBest-corrected visual acuity and CMT improved in all patients, (p&lt;0.05, for both groups). Mean number of HRS decreased after both treatments (p&lt;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&lt;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). ConclusionHigher 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

Diabetic macular edema : Correlation between microperimetry and optical coherence tomography findings

PURPOSE. To compare the changes in macular sensitivity (microperimetry) and macular thickness with different degrees of diabetic macular edema. METHODS. Sixty-one eyes of 32 consecutive diabetic patients were included in this cross-sectional study. All included eyes underwent functional and morphologic examination of the macular area. Best corrected visual acuity (ETDRS charts), macular sensitivity, and macular thickness were quantified. Lesion-related macular sensitivity and retinal fixation were investigated with an advanced, automatic microperimeter. Optical coherence tomography (OCT) was used to quantify macular thickness. RESULTS. The 61 included eyes were graded, by two retinal specialists, for diabetic macular edema as follows: 16 were graded as no macular edema (NE), 30 as non-clinically significant macular edema (NCSME), and 15 as clinically significant macular edema (CSME). Macular thickness significantly increased from the NE to the CSME group (P &lt; 0.0001), whereas macular sensitivity significantly decreased from the NE to the CSME group (P &lt; 0.0021). A significant correlation coefficient was noted between retinal sensitivity and normalized macular thickness (r = -0.37, P &lt; 0.0001). Linear regression analysis showed a decrease of 0.83 dB (P &lt; 0.0001) for every 10% of deviation of retinal thickness from normal values. Visual acuity and central macular sensitivity correlated significantly in the NCSME group (r = -0.6, P = 0.0008), but not in the NE (r = -0.144, P = 0.6) or in the CSME (r = -0.46, P = 0.11) groups. CONCLUSIONS. Macular edema may be better documented by adding macular sensitivity mapping by microperimetry to macular thickness measurement by OCT and visual acuity determination because macular sensitivity seems to be a relevant explanatory variable of visual function, independent of macular thickness data. Moreover, microperimetry may be of value in predicting the outcome of diabetic macular edema, because it incorporates a functional measure that may supplement the predictive value of OCT and visual acuity. Copyright © Association for Research in Vision and Ophthalmology

Aqueous Humor Biomarkers of Müller Cell Activation in Diabetic Eyes

Purpose: To identify early biomarkers of retinal Müller cell activation in diabetic eyes with or without clinically detectable signs of diabetic retinopathy (DR). Methods: 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. Results: 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 &lt; 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. Conclusions: 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

Proteome analysis of retinal glia cells-related inflammatory cytokines in the aqueous humour of diabetic patients

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 &lt; 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

Optic pathway glioma in type 1 neurofibromatosis: Review of its pathogenesis, diagnostic assessment, and treatment recommendations

Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15-20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome. In addition, we discussed the recent findings on the pathophysiology of OPG development in NF1. This review provides a comprehensive overview about the clinical management of NF1-associated OPG, focusing on the most recent advances from preclinical studies with genetically engineered models and the ongoing clinical trials