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Purpose: To analyze the macular function of eyes with macular-foveal capillaries (MFC), a condition characterized by the absence of the foveal avascular zone (FAZ), identified by optical coherence tomography angiography., Methods: Eight eyes with MFC at optical coherence tomography angiography and normal visual acuity were consecutively recruited. Eight eyes of healthy subjects were enrolled as healthy controls. All eyes underwent optical coherence tomography, optical coherence tomography angiography, best-correct visual acuity, low-luminance visual acuity, contrast sensitivity measurement, colour vision tests, and both mesopic and scotopic microperimetry., Results: Best-corrected visual acuity, low-luminance visual acuity, contrast sensitivity, and colour vision tests did not differ between the two groups. At mesopic microperimetry, both foveal retinal sensitivity and mean mesopic retinal sensitivity of the central 1° were statistically inferior in MFC versus control eyes (P < 0.0001 and P < 0.0001, respectively). At scotopic microperimetry, a dense foveal scotoma, normally present in control eyes, was completely lacking in MFC eyes. Scotopic foveal retinal sensitivity was statistically superior in MFC versus control eyes (P = 0.009)., Conclusion: The absence of the foveal dense scotoma in scotopic conditions underlines that the foveal rod-free zone is not present when capillaries are present in this area. An anomalous foveal distribution of photoreceptors, with both rods and cones present in this area, may be postulated in MFC eyes.

Purpose: To evaluate the prevalence, the vascular features, and the clinical diagnostic implication of retinal vascular abnormalities (RVAs) associated with neurofibromatosis Type 1 (NF1) in a large cohort of patients., Methods: Two hundred and ninety-four patients affected by NF1 were consecutively enrolled. The presence of RVAs was detected by means of infrared confocal scanning laser ophthalmoscopy images. Three hundred age- and race-matched healthy subjects were enrolled as a healthy control group. Fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography were also performed in patients with RVAs., Results: Retinal vascular abnormalities were detected in 18 patients with NF1 (6.1%) and in none of the healthy subjects. Retinal vascular abnormalities appeared in all cases as well-defined, small, tortuous retinal vessels with a spiral aspect, originating from small tributaries of retinal veins. The presence of RVAs did not correlate with the presence of other specific ocular or systemic NF1 features (P > 0.05). On optical coherence tomography angiography, RVAs appeared as an isolated tortuous vessel of the superficial vascular plexus in all cases, associated with localized anomalous crowded and congested capillary network of the deep vascular plexus in 75% of cases., Conclusion: Retinal vascular abnormalities are present in a limited proportion of patients affected by NF1 and can be considered an additional distinctive sign of the disease.

Objective: To compare static (during a pure fixation task) versus dynamic (during microperimetry) quantification of fixation stability using microperimetry in normal and pathologic eyes, by means of 2 available (clinical and bivariate contour ellipse area [BCEA]) classification methods., Design: Prospective comparative observational study., Participants: One hundred and forty-nine eyes (110 patients) with different macular diseases and 171 normal eyes (109 subjects)., Methods: In all eyes studied, fixation stability was acquired during an isolated fixation task (static fixation) and during microperimetry (dynamic fixation). All fixation data were analyzed and compared by means of a clinical classification and by means of BCEA quantification., Results: Pathologic eyes were classified as follows: 41 eyes with diabetic macular edema (DME group), 13 eyes with vitreoretinal interface disease, 60 eyes with age-related macular degeneration (AMD group), and 35 eyes with primary open-angle glaucoma. Fixation stability was not uniform among groups according to clinical classification in both static and dynamic modalities (p < 0.0001). AMD group showed larger BCEA areas compared with all other groups (p < 0.0001). All pathologic groups showed more unstable fixation in dynamic fashion according to both clinical and BCEA methods (p < 0.0001). The variation of fixation stability of control group in dynamic task was highlighted only by BCEA analysis (p < 0.0001). A deterioration of retinal fixation according to clinical method matches a significant increase in BCEA areas (p < 0.0001)., Conclusions: The detection of clinical fixation stability changes improves when acquired in the dynamic modality. BCEA analysis provides more accurate evaluation of fixation stability and may detect minimal quantitative changes of the fixation area. However, a standard clinical classification can also detect changes in fixation stability in pathologic eyes. Both methods are useful tools in the evaluation of fixation stability., (© 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

To describe the optical coherence tomography (OCT), the standard short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF), and the microperimetric findings in a child with a unique unilateral lesion of the temporal macula previously called torpedo maculopathy. A 4-year-old female with torpedo maculopathy was evaluated with spectral-domain OCT (SD-OCT), standard SW-FAF (excitation 488 nm, emission >500 nm) and NIR-FAF (excitation 787 nm, emission >800 nm). Microperimetry was performed to assess retinal sensitivity changes correlated to the macular lesion. SD-OCT showed an abnormally thin retinal pigment epithelium signal and an increased signal transmission in the choroid corresponding to the torpedo lesion with no neuroretinal changes. SW-FAF resulted in normal fluorescence of the lesion except for a small hyperfluorescent area at the tail level. NIR-FAF showed hypofluorescence corresponding to the lesion. Macular microperimetry showed reduced retinal sensitivity along the pigmented margins of the lesion with normal values over the lesion. The patient was re-evaluated 12 months later and no change was documented with all diagnostic techniques. This case supports a congenital defect of retinal pigment epithelium. The absence of both functional changes at lesion level and neuroretinal changes at OCT may depend on the very early detection of this lesion.

Purpose: To investigate the use of high-resolution ultrasonography for detecting choroidal layer abnormalities in eyes with central serous chorioretinopathy (CSC)., Design: Prospective observational case series., Method: Optical coherence tomography (OCT) and high-resolution ultrasonography with a 20-MHz immersion probe were performed bilaterally in 10 patients, of whom 5 were affected by unilateral active CSC and 5 by unilateral cystoid macular edema (CME). Ten age-matched control subjects were also investigated., Results: Both OCT and high-resolution ultrasonography showed a macular elevation in eyes with CSC and CME. High-resolution ultrasonography has shown evidence of a nonechogenic linear band under the retinal pigment epithelium in patients affected by CSC. This could be found in neither patients with CME or in control subjects., Conclusion: High-resolution ultrasonography can detect a nonechogenic space consistent with hyperpermeability of choroidal capillaries in eyes with active CSC. Shadowing by an altered retinal pigment epithelium cannot be ruled out, however.

Optical coherence tomography (OCT) allows us to identify, into retinal layers, new morphological entities, which can be considered clinical biomarkers of retinal diseases. According to the literature, solitary, small (<30 µm), medium level hyperreflective (similar to retinal fiber layer) retinal foci (HRF) may represent aggregates of activated microglial cells and an in vivo biomarker of retinal inflammation. The identification and quantification of this imaging biomarker allows for estimating the level and possibly the amount of intraretinal inflammation in major degenerative retinal disorders, whose inflammatory component has already been demonstrated (diabetic retinopathy, age-related macular degeneration, radiation retinopathy). Currently, diabetic retinopathy (DR) probably represents the best clinical model to apply this analysis in the definition of this clinical biomarker. However, the main limitation to the clinical use of HRF is related to the technical difficulty of counting them: a time-consuming methodology, which also needs trained examiners. To contribute to solve this limitation, we developed and validated a new method for the semi-automatic detection of HRF in OCT scans. OCT scans of patients affected by DR, were analyzed. HRF were manually counted in High Resolution spectral domain OCT images. Then, the same OCT scans underwent semi-automatic HRF counting, using an ImageJ software with four different settings profiles. Statistical analysis showed an excellent intraclass correlation coefficient (ICC) between the manual count and each of the four semi-automated methods. The use of the second setting profile allows to obtain at the Bland–Altman graph a bias of −0.2 foci and a limit of agreement of ±16.3 foci. This validation approach opens the way not only to the reliable and daily clinical applicable quantification of HRF, but also to a better knowledge of the inflammatory component—including its progression and regression changes—of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the individual value and the contribution of color fundus photography (CFP) and optical coherence tomography (OCT) in the screening of age-related macular degeneration (AMD) of an unselected population. Methods: CFP and OCT images of 15957 eyes of 8069 subjects older than 55 years, obtained during a population-based screening for AMD using a single diagnostic non-mydriatic imaging device, were analyzed by a blinded examiner. The two techniques were preliminary evaluated considering the dichotomous parameter "gradable/ungradable", then gradable images were classified. CFP were graded according to the standardized classification of AMD lesions. OCT images were also categorized considering the presence of signs of early/intermediate AMD, late AMD, or other retinal diseases. Another blinded operator re-graded 1978 randomly selected images (for both CFP and OCT), to assess test reproducibility. Results: Of the 15957 eyes, 8356 CFP (52.4%) and 15594 (97.7%) OCT scans were gradable. Moreover, most of the eyes with ungradable CFP (7339, 96.6%) were gradable at OCT. AMD signs were revealed in 7.4% of gradable CFP and in 10.4% of gradable OCT images. Moreover, at OCT, AMD signs were found in 1110 (6.9%) eyes whose CFP were ungradable or without AMD (847 and 263 eyes, respectively). The inter-operator agreement was good for the gradable versus ungradable parameter, and optimal for the AMD grading parameter of CFP. The agreement was optimal for all OCT parameters. Conclusions: OCT provided gradable images in almost all examined eyes, compared to limited CFP efficiency. Moreover, OCT images allowed to detect more AMD eyes compared to gradable photos. OCT imaging appears to significantly improve the power of AMD screening in a general, unselected population, compared to CFP alone. [ABSTRACT FROM AUTHOR]

Purpose: To compare the foveal avascular zone (FAZ) area measurements produced by different optical coherence tomography angiography (OCTA). Methods: Healthy enrolled volunteers underwent OCTA using 2 different devices: Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany) and RS-3000 Advance (Nidek, Gamagori, Japan). Two graders measured FAZ in both superficial (SCP) and deep (DCP) retinal capillary plexuses. The SCP and DCP en face images were visualized automatically segmenting 2 separate slabs defined by the arbitrary segmentation lines created by the software of each OCT device. One grader repeated each measure twice. Results: Fifty-nine eyes were included. The mean FAZ was 0.33 ± 0.09 mm2 at the SCP and 0.57 ± 0.17 mm2 at the DCP measured with RS-3000 versus 0.30 ± 0.08 and 0.35 ± 0.08 mm2, respectively, measured with Spectralis. The measurements of the 2 devices were significantly different (p < 0.0001). The intraoperator agreement was excellent at the SCP (intraclass correlation coefficient, ICC: 0.97 with Spectralis and 0.96 with RS-3000). At the DCP, it was good with Spectralis and fair with RS-3000 (ICC: 0.85 and 0.64, respectively). The interoperator agreement was excellent for Spectralis and good for RS-3000 at the SCP (ICC: 0.97 and 0.93, respectively). It was good at the DCP with both devices (ICC: 0.74 with RS-3000 and 0.81 with Spectralis). Conclusions: FAZ measurements obtained with different OCTA devices differ. These findings should be considered in follow-up studies of patients with retinal vascular diseases. [ABSTRACT FROM AUTHOR]

Purpose To analyse changes in choroidal thickness and retinal sensitivity (Se) in patients with geographic atrophy (GA) with or without choroidal neovascularisation (CNV) in the fellow eye. Participants Patients with bilateral GA (B-GA group) and patients with unilateral GA and CNV in the fellow eye (U-GA group) were followed every 6 months, and enhanced depth imaging optical coherence tomography (OCT), blue and near infrared-wavelength fundus autofluorescence (B- and NIR-FAF), and microperimetry were evaluated. Methods GA area, choroidal thickness, and Se were measured in the eye with GA at baseline and every 6 months up to the last follow-up visit. Results 19 patients (8 in the B-GA group (16 eyes) and 11 in the U-GA group (11 eyes)) were studied. The mean±SD follow-up was 1.66±0.71 years (range 0.74-2.60 years) in the U-GA group, and 1.51±0.86 years (range 0.58-2.95 years) in the B-GA group (p=0.6766). Mean GA area was not significantly different between groups at baseline (p=0.4118 in the B-FA and p=0.6806 in the NIR-FAF) or at follow-up (p=0.5734 in the B-FAF and p=0.8945 in the NIR-FAF). Mean GA area significantly increased in both groups during follow-up (p=0.0050 for B-FAF and p=0.0052 for NIR-FAF in the U-GA group; p=0.0049 for B-FAF and p=0.0072 for NIR-FAF in the B-GA group). Choroidal thickness was significantly greater in the B-GA group compared with the U-GA group both at baseline (mean choroidal thickness 170.5±78.5 μm vs 129.1 ±36.1 μm; p=0.0371) and at last follow-up (173.2 ±86.1 μm vs 123±32.1 μm; p=0.0340). During followup mean choroidal thickness significantly decreased only in the U-GA group (p=0.0276); conversely mean Se significantly decreased only in B-GA group (p=0.0405). Conclusions During follow-up, changes in Se and choroidal thickness differed in patients with GA with or without CNV in the fellow eye. These results identify at least two GA phenotypes, in which the development and progression of GA may be primarily due to different pathophysiologic mechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: The in vivo optical coherence tomography analysis of the biomarkers of retinal microglia and macroglia in Von Hippel–Lindau disease represents an innovative field of research. The different behavior of these glial cells in Von Hippel–Lindau patients provides new data regarding the pathophysiology of retinal hemangioblastoma, the most common ocular manifestation of this hereditary disorder. Moreover, these biomarkers show a different behavior in Von Hippel–Lindau patients in relation to the presence or absence of retinal hemangioblastoma. Therefore, we can hypothesize that retinal hemangioblastoma is mainly due to the activation of macroglia by previously activated microglial cells. Background: Von Hippel–Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients. Methods: The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia. Results: 61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients (p < 0.05) and in VHL without RH (p < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH (p < 0.05). The thickness of mRNFL (p < 0.0001) and GCL (p < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL (p < 0.0001) and GCL (p < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower (p < 0.05) in the eyes of VHL patients with RH, than in those without RH. Conclusions: The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease. [ABSTRACT FROM AUTHOR]

. 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. [ABSTRACT FROM AUTHOR]

To investigate fixation pattern and retinal sensitivity in patients with serpiginous choroiditis (SC). Twenty-eight eyes (14 patients) with SC were evaluated. Best-corrected visual acuity, color fundus photography, fundus autofluorescence, and fluorescein and indocyanine green angiography were performed. Microperimetry was used to assess fixation pattern and retinal sensitivity. Of 28 eyes, 16 (57%) had central, one (4%) poor central, and 11 (39%) eccentric fixation; and 18 (64%) had stable, four (14%) relatively unstable, and six (21%) unstable fixation. In patients with posterior pole symmetrically involved in both eyes, the better eye had stable and central fixation in all cases. Atrophic lesions were characterized by a dense scotoma in all cases, with a relative scotoma at their margins in ten eyes (38%). In two cases of active disease, a dense scotoma correlated to an active lesion could be detected. A relative scotoma was documented in areas not involved by the disease at the posterior pole in eight eyes (28%), and in the peripapillary area in 11 eyes (39%). Quantification of retinal sensitivity and fixation pattern by microperimetry offers new data about the impact of visual impairment in patients with SC. A reduction of retinal sensitivity in an apparently healthy area suggests a wider functional involvement of the retina, undetectable by morphologic evaluation alone. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the effects of subfoveal choroidal neovascularizzation (CNV) secondary to age-related macular degeneration (AMD) on macular functional parameters quantified with an automatic fundus perimeter. Methods. 118 eyes of 98 consecutive patients with subfoveal CNV secondary to AMD were evaluated. Best corrected visual acuity (ETDRS charts), fundus photography, and fluorescein angiography were performed. Microperimetry (fundus-related perimetry) was used to quantify macular sensitivity and fixation pattern (location and stability). Results. Of 118 eyes: 26 (21.9%) had central, 18 (15.1%) poor central and 74 (63.0%) eccentric fixation; 31 (26.0%) had stable, 42 (35.6%) relatively unstable and 45 (38.4%) unstable fixation. In 75 eyes (63.4%) a dense central scotoma was found. Angiographic classification of subfoveal CNV (occult versus classic) was not significantly related to fixation pattern (location: P = 0.274; stability: P = 0.385), and presence of dense scotoma (P = 0.41). Conclusion. Microperimetric quantification of macular sensitivity and fixation pattern in eyes with subfoveal CNV secondary to AMD offers new data about the impact of visual impairment in these eyes. Moreover, microperimetry improves the functional evaluation of subfoveal CNV in AMD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if simple- or multiple-field digital color nonmydriatic (NM) retinal images can replace 7 standard stereoscopic fundus photographs in the screening of diabetic retinopathy (DR). Design: Prospective, masked, comparative case series. Methods: One hundred and eight eyes of 55 diabetics were studied to determine single lesions and to grade clinical levels of DR and diabetic macular edema (DME) using both 1 and 3 NM digital color retinal images compared with the Early Treatment Diabetic Retinopathy Study (ETDRS) 7 standard 35-mm stereoscopic color fundus photographs (7F-ETDRS). All eyes underwent NM 45-degree field images of 1 central field (1F-NM), NM 45-degree field images of 3 fields (3F-NM), and, after pupil dilatation, 30-degree 7F-ETDRS photography. Images were analyzed by 2 independent, masked retinal specialists (S.V. and E.B.), lesion-by-lesion according to the ETDRS protocol and for clinical severity level of DR and DME according to the international classification of DR. Results: Using 7F-ETDRS as the gold standard, agreement was substantial for grading clinical levels of DR and DME (κ = 0.69 and κ = 0.75) vs 3F-NM; moderate for DR level (κ = 0.56) and substantial for DME (κ = 0.66) vs 1F-NM; almost perfect for detecting presence or absence of DR (κ = 0.88) vs both 1F-NM and 3F-NM; and almost perfect for presence or absence of DME (κ = 0.97) vs 3F-NM and substantial (κ = 0.75) vs 1F-NM. Sensitivity and specificity for detecting referable levels of DR were 82% and 92%, respectively, for 3F-NM and 71% and 96%, respectively, for 1F-NM. Conclusions: Three color 45-degree NM fundus fields may be an effective tool in a screening setting to determine critical levels of DR and DME for prompt specialist referral. One central 45-degree image is sufficient to determine absence or presence of DR and DME, but not for grading it. [Copyright &y& Elsevier]