Luisa Pierro

Enhanced depth imaging optical coherence tomography in type 2 diabetes.

PURPOSE To investigate the changes in macular choroidal thickness in eyes with various stages of diabetic retinopathy, using enhanced depth imaging optical coherence tomography (EDI OCT). METHODS Sixty-three consecutive diabetic patients--who presented without diabetic retinopathy (NDR); with diabetic retinopathy (nonproliferative diabetic retinopathy [NPDR]) and no clinically significant macular edema (CSME-); or with NDPR and clinically significant macular edema (CSME+)--underwent EDI OCT. Twenty-one age- and sex-matched healthy subjects (21 eyes) also underwent EDI OCT. RESULTS A total of 63 eyes of 63 consecutive diabetic patients (26 female [41.2%]; mean age 65 ± 9 years, range 48-83 years) were included in the analysis. Mean best-corrected visual acuity was 0.13 ± 0.25 LogMAR (range 0-1). Mean CMT was 272.5 ± 16.2 μm in 21 NDR eyes, 294.5 ± 23.5 μm in 21 NPDR/CSME- eyes, and 385.6 ± 75.1 μm in 21 NPDR/CSME+ eyes. There was no difference in mean subfoveal choroidal thickness among each diabetic group (238.4 ± 47.9 μm [NDR], 207.0 ± 55.9 μm [NPDR/CSME-], 190.8 ± 48.4 μm [NPDR/CSME+]; P = 0.23). The mean subfoveal choroidal thickness was significantly reduced in each diabetic group compared with the control group (309.8 ± 58.5 μm, P < 0.001). CONCLUSIONS In diabetic eyes, there is an overall thinning of the choroid on EDI OCT. A decreased choroidal thickness may lead to tissue hypoxia and consequently increase the level of VEGF, resulting in the breakdown of the blood-retinal barrier and development of macular edema.

Retinal nerve fiber layer thickness reproducibility using seven different OCT instruments.

PURPOSE The clinical utility of new optical coherence tomography (OCT) instruments strongly depends on measurements reproducibility. The aim of this study was to assess retinal nerve fiber layer (RNFL) thickness reproducibility using six different spectral-domain OCTs (SD-OCTs) and one time-domain OCT. METHODS RNFL thickness (average and four quadrant) from six SD-OCTs (Spectral OCT/SLO OPKO/OTI, 3D-OCT 2000 Topcon, RS-3000 NIDEK, Cirrus HD-OCT Zeiss, RTVue-100 Optovue, and Spectralis Heidelberg) and one time-domain OCT (Stratus OCT Zeiss) was measured twice in 38 right eyes of 38 randomly chosen healthy volunteers by two masked operators. Inter- and intraoperator reproducibility was evaluated by the intraclass correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman test analysis. Instrument-to-instrument reproducibility was determined by ANOVA for repeated measures. We also tested how the devices disagree in terms of systemic bias and random error using a structural equation model. RESULTS Mean RNFL average thickness ranged from 90.08 μm to 106.51 μm. Cirrus and Heidelberg showed the thinnest RNFL values in all measurements, Topcon the highest. ICC, CV, and Bland-Altman plots showed variable inter- and intraoperator agreement depending on the instrument. Heidelberg demonstrated the best interoperator (ICC, 0.92; CV, 1.56%) and intraoperator (ICC, 0.94 and 0.95; CV, 1.28% and 1.26%, respectively, for operator A and operator B) agreement for average RNFL thickness. CONCLUSIONS Heidelberg demonstrated the higher agreement in inter- and intraoperator reproducibility, Optovue the worst. In light of our error analysis results, we found that a scale bias among instruments could interfere with a thorough RNFL monitoring, suggesting that best monitoring is obtained with the same operator and the same device.

Macular Thickness Interoperator and Intraoperator Reproducibility in Healthy Eyes Using 7 Optical Coherence Tomography Instruments

PURPOSE To evaluate macular thickness measurement reproducibility using 6 new spectral-domain (SD) optical coherence tomography (OCT) devices and 1 time-domain OCT device DESIGN Prospective, observational study. METHODS setting: Clinical practice. study population: Macular thickness was assessed in 18 randomly chosen consecutive eyes of 18 healthy volunteers by 2 masked operators using 6 SD OCT devices and 1 time-domain OCT device. main outcome measures: Intraoperator and interoperator reproducibility of OCT-measured central macular thickness. RESULTS Mean macular thickness ranged from 172.77 to 272.87 microm. Intraobserver Intraclass coefficient correlation ranged from 0.75 to 0.96. Intraobserver coefficient of variation ranged from 0.44 to 2.75. In Bland-Altman analysis, interoperator mean difference ranged from 0.22 to -9.69. An analysis of variance used for repeated measurement was statistically significant for instruments (P < .001) and operators (P = .04), but not for instruments x operators (P = .32). CONCLUSIONS The 7 OCT devices presented differing macular thickness measurement values; the lowest value was with Copernicus, and the highest was with Spectralis HRA+OCT (Heidelberg Engineering). The new generation of SD OCT devices has good intraoperator reproducibility, but the Spectralis presents the highest reproducibility together with the best interoperator agreement. The software, and in particular the algorithm, used is the most important factor regarding reproducibility differences in macular thickness measurement. The main result of our study is that macular thickness absolute value differs for each device. For this reason, the devices are not interchangeable.

Axial length in patients with diabetes.

PURPOSE To investigate the relationship between axial length and retinal involvement in patients with diabetes. METHODS A total of 157 consecutive patients with diabetes underwent biometry. The patients were divided into three groups, according to retinopathy: 44 without retinopathy, 37 with background retinopathy, and 76 with proliferative retinopathy. To compare axial length in diabetic versus nondiabetic subjects, a control group of 157 healthy subjects with age and sex distribution similar to the diabetic group was selected from an orthopedic clinic. We investigated in the diabetic group whether the axial length was related to specific type of diabetes (non-insulin-dependent or insulin-dependent), duration of disease, presence of retinopathy, or laser treatment. To eliminate the confounding effect of myopia, we excluded all patients with axial length greater than 24 mm from the two groups. Comparison of diabetic patients without retinopathy versus nondiabetic subjects was also performed. RESULTS Diabetic patients presented shorter axial lengths compared with the controls (mean +/- standard deviation, 22.4+/-1.3 mm versus 23.4+/-1.3 mm; P<0.001). Significantly shorter axial lengths were found in the background and proliferative retinopathy groups compared with the group without retinopathy (22.0+/-1.2 mm and 22.1+/-1.1 mm versus 23.2+/-1.4 mm, respectively; P<0.05). No difference in axial length was found between the diabetic patients without retinopathy and the nondiabetic subjects (P = 0.3). Multivariate analyses showed that retinopathy was negatively correlated with axial length (P<0.01). Including only the patients with axial length under 24 mm, we obtained similar results. CONCLUSION Axial length is shorter in diabetic patients than in nondiabetic subjects. Within the diabetic group, patients with retinopathy had shorter axial lengths than did patients without retinopathy.

Evidence for retrochiasmatic tissue loss in Leber's hereditary optic neuropathy

Patients with Lebers hereditary optic neuropathy (LHON) have loss of central vision with severe damage of small‐caliber fibers of the papillomacular bundle and optic nerve atrophy. The aim of this study was to define the presence and topographical distribution of brain grey matter (GM) and white matter (WM) injury in LHON patients using voxel‐based morphometry (VBM). The correlation of such changes with neuro‐ophthalmologic findings and measurements of peripapillary retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) was also assessed. Dual‐echo and fast‐field echo scans were acquired from 12 LHON patients and 12 matched controls. VBM analysis was performed using SPM5 and an ANCOVA model. A complete neuro‐ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary RNFL thickness measurements were obtained in all the patients. Compared with controls, average peripapillary RNFL thickness was significantly decreased in LHON patients. LHON patients also had significant reduced GM volume in the bilateral primary visual cortex, and reduced WM volume in the optic chiasm, optic tract, and several areas located in the optic radiations (OR), bilaterally. Visual cortex and OR atrophy were significantly correlated with average and temporal peripapillary RNFL thickness (P < 0.001; r values ranging from 0.76 to 0.89). Brain damage in patients with LHON is not limited to the anterior visual pathways, but extends posteriorly to the OR and the primary visual cortex. Such a damage to the posterior parts of the visual pathways may be due either to trans‐synaptic degeneration secondary to neuroaxonal damage in the retina and optic nerve or to local mitochondrial dysfunction. Hum Brain Mapp, 2010.

Vessel density analysis in patients with retinitis pigmentosa by means of optical coherence tomography angiography

Aims To describe the vascular abnormalities in patients affected by retinitis pigmentosa (RP) by means of optical coherence tomography angiography (OCT-A). Methods Cross-sectional case series; patients with RP presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Inclusion criteria were: diagnosis of RP, clear ocular media, adequate pupillary dilation, and stable fixation. Patients underwent best-corrected visual acuity (BCVA), biomicroscopy, short-wavelength fundus autofluorescence (SW-FAF), and 3×3 Swept Source OCT-A. 30 healthy subjects were chosen as controls. The main outcome was identification of abnormalities in density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), along with abnormalities of the choriocapillaris (CC). Results 16 patients (32 eyes) were recruited (6 females, 37.4%). Mean age was 53±18 years; mean BCVA was 0.5±0.3 LogMAR. Vessel density analysis disclosed a statistical significant difference in the SCP (29.5±6.8 vs 34.1±4.3; p=0.009) and in the DCP (28.7±7.5 vs 35.5±5.7; p=0.001) between the patients and the controls. No difference was found at the level of the CC (51±4.4 vs 51.3±2.2; p=0.716). RP patients showed a bigger foveal avascular zone at the DCP level compared to controls (p<0.001). Conclusions This study showed that most of the vascular impairment in patients affected by RP localised in the DCP, with relative sparing of the SCP and CC. DCP alterations were more pronounced outside the hyper-autofluorescent ring on SW-FAF. Vascular impairment may preclude good treatment outcomes in RP patients.

Vascular abnormalities in patients with Stargardt disease assessed with optical coherence tomography angiography

Aims To describe the vascular abnormalities in patients affected by Stargardt disease (STGD1) by means of optical coherence tomography angiography (OCT-A). Methods Cross-sectional case series, with the following inclusion criteria: diagnosis of STGD1, clear ocular media, and stable fixation. Patients underwent best-corrected visual acuity (BCVA), biomicroscopy, applanation tonometry, short-wavelength fundus autofluorescence (SW-FAF) (HRA Heidelberg, Germany), 3×3 Swept Source OCT-A (Topcon Corporation, Japan). Foveal avascular zone (FAZ) area was manually outlined and removed from the vessel density analysis (ImageJ). Main outcome was vessel density assessment in the superficial capillary plexus (SCP), in the deep capillary plexus (DCP), and in the choriocapillaris (CC) of patients with STGD1. Results Nineteen patients (36 eyes) were recruited for the study (10 females, 52.6%). Mean age was 33±5.7 years and mean BCVA was 0.6±0.3 logarithm of the minimum angle of resolution. Thirty-six healthy age-matched subjects (one eye for each patient) acted as a control group. Qualitative analysis of OCT-A revealed areas of reduced vascular density in superficial and DCPs. CC showed focal defects partially corresponding to the flecks on SW-FAF imaging. Quantitative analysis of OCT-A disclosed a statistically significant difference in the density of the SCP (0.302±0.062 vs 0.365±0.042; p=0.0002) and the DCP (0.303±0.081 vs 0.399±0.045; p<0.001) compared with controls. To analyse CC, patients with STGD1 were divided into two groups, according to the presence of chorioretinal atrophy. Patients with atrophy showed significantly lower CC density compared with controls (p=0.0003) and patients without atrophy (p=0.001). Patients with STGD1 showed a larger FAZ at the SCP level compared with controls (p=0.012). Conclusions Vascular impairment in patients affected by STGD1 is concentrated in superficial and the deep retinal plexuses. Patients with atrophic changes have a greater reduction in CC density compared with controls (‘dark atrophy’). Morphological vascular evaluation may become an important step for predicting STGD1 treatment outcomes.

Optical coherence tomographic hyperreflective foci in early stages of diabetic retinopathy

Purpose: To analyze the presence of hyperreflective foci in Type 1 and Type 2 diabetic patients, separately, without clinically significant diabetic macular edema and visual impairment. Methods: Noninvasive, observational prospective study. Seventeen and 19 consecutive Type 1 and Type 2 diabetic patients (33 and 38 eyes), respectively, were recruited. All patients had no clinically significant diabetic macular edema or visual impairment. Two age- and sex-matched control groups were also included. Patients underwent an ophthalmologic examination including spectral domain optical coherence tomography. Hyperreflective foci were counted considering horizontal B-scan passing through the fovea. Results: On spectral domain optical coherence tomography, patients affected by Type 1 and Type 2 diabetes had a mean of 7.5 ± 4.6 and 9.9 ± 4.5 hyperreflective foci, respectively. Subjects of control groups had a mean of 0.9 ± 0.8 and 1.7 ± 1.5 hyperreflective foci, respectively. Hyperreflective foci amount was statistically different between Type 1 and Type 2 diabetic groups (P = 0.032) and significantly higher in diabetic patients than in controls (P < 0.001). Hyperreflective foci amount was significantly higher in diabetic patients with a poor quality glycometabolic control (P < 0.001 and P = 0.016) or affected by hypertension (P = 0.008). Conclusion: We reported the presence of hyperreflective foci in diabetic patients without diabetic macular edema and visual impairment. This spectral domain optical coherence tomography finding might be a useful marker for the diagnosis and the follow-up in the early stage of diabetic retinopathy.

Axial Length and Refraction in Retinal Vein Occlusions

To assess whether axial length and refraction are risk factors for retinal vein occlusion, we measured these parameters in 88 consecutive patients with unilateral branch retinal vein occlusion (BRVO), in 58 consecutive patients with unilateral central retinal vein occlusion (CRVO) and in 50 patients selected as a control group. Patients and controls were free or affected by systemic or local predisposing factors. We compared eyes with CRVO with control eyes, eyes with BRVO with control eyes, and eyes with CRVO with eyes with BRVO. Comparing CRVO eyes and controls, none of the investigated variables was shown to be significant. From the analysis of BRVO eyes versus controls, it resulted that refraction was the only variable which played the role of an independent prognostic factor. When comparing BRVO eyes with CRVO eyes, we found that age was slightly related to the development of BRVO. In conclusion, faulty refraction appeared to be a risk factor for the development of BRVO. We did not find any influence of axial length on the occlusion of retinal veins.

Choroidal impairment and macular thinning in patients with systemic sclerosis: the acute study.

Raynauds phenomenon (RP) is a reversible vasospastic response of the extremities to cold or emotion, and can be the first manifestation or may be present before the development of an overt systemic sclerosis (SSc). The disturbance of the balance between vasodilation and vasoconstriction is not limited to the peripheral microcirculation of the skin, but it is also observed in other organs, such as the choroidal plexus of the eye. We aimed to examine the choroidal thickness (CT), the macular thickness and ganglion cell complex (GCC) average in thirty consecutive patients, without visual symptoms, classified as primary RP (pRP), RP secondary to suspected SSc, and overt SSc. All the patients underwent rheumatologic and ophthalmologic examination, capillaroscopy, test for anti-nuclear antibodies, anti-dsDNA, and anti-extractable nuclear antigens. Ophthalmologic examination included: best corrected visual acuity; slit lamp biomicroscopy; intraocular pressure measurements, fundus examination, and Spectral Domain-Optical Coherence Tomography (SD-OCT) with enhanced depth imaging scan system. Twenty-seven healthy subjects similar for gender and age were analyzed. In pRP, CT was significantly thinner than controls in the outer nasal and temporal regions. In secondary RP, the inner and outer nasal areas were significantly thinner than controls. In SSc, the central, inner inferior, inner nasal, inner superior, outer temporal, outer inferior, and outer nasal regions were significantly thinner than controls. A decreasing trend of central foveal thickness was noted. All the patients had GCC average significantly lower than controls. A thinning of choroidal and macular thickness, as well as of GCC was observed in patients with pRP and becomes more severe and extensive in RP secondary to suspected SSc and overt SSc. To our knowledge, this is the first study to analyze the choroidal features using SD-OCT in RP. These data may be clinically useful in suggesting an early involvement of ocular microcirculation with significant reduction of choroidal perfusion.