Mario Cigada

Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Layer Thickness in Alzheimer's Disease Using Spectral-Domain Optical Coherence Tomography

PURPOSE To evaluate differences between the retinal nerve fiber layer (RNFL) thickness and RNFL + ganglion cell layer (GCL) thickness in patients affected by Alzheimers disease (AD) and healthy patients using spectral-domain optical coherence tomography (SD-OCT). METHODS This was a case-control prospective study. Twenty-one AD patients and 21 healthy subjects underwent neurological examination, clock-drawing test (CDT), Mini Mental State Examination (MMSE), and comprehensive ophthalmic evaluation with visual acuity. SD-OCT examination was performed using Spectralis and RTVue-100. An RNFL thickness map was obtained using the Spectralis volume protocol with 19 lines on the 30° field centered on the macula. On each B-scan, the outer RNFL limit was manually set. Statistical analysis was performed to assess interoperator RNFL evaluation thickness. An RNFL+GCL thickness map was obtained using the RTVue-100 MM6 protocol. Maps were divided into the nine ETDRS subfields and each map value in every area was evaluated. A single eye from each patient was randomly chosen to perform the analysis. Differences between AD and healthy subjects were assessed. RESULTS The two study groups were age and sex matched. MMSE results were 19.9 ± 3.1 and 27.9 ± 1.3, respectively (P < 0.001). There was good agreement in the manual delimitation of the RNFL layer. There was a significant difference in the thickness of both the RNFL and the RNFL+GCL in all examined fields. For example, in the inferior internal subfield, the RNFL thickness was 28.1 ± 3.1 μm for AD patients and 32.6 ± 3.8 μm for healthy subjects (P < 0.001). CONCLUSIONS These results indicate that RNFL and RNFL+GCL thickness measurements are reduced in AD patients compared with healthy subjects. This finding may represent a useful element for the diagnosis and follow-up of this pathology.

Autonomic Changes During Hypnosis: A Heart Rate Variability Power Spectrum Analysis as a Marker of Sympatho-Vagal Balance

Spectral analysis of beat-to-beat variability in electrocardiography is a simple, noninvasive method to analyze sympatho-vagal interaction. The electrocardiogram is analyzed by means of an automatic, autoregressive modeling algorithm that provides a quantitative estimate of R-R interval variability by the computation of power spectral density. Two major peaks are recognizable in this specter: a low-frequency peak (LF, -0.1 Hz), related to the overall autonomic activity (ortho+parasympathetic) and a high-frequency peak (HF, -0.25 Hz), representative of the vagal activity. The LF/HF ratio is an index of the sympatho-vagal interaction. This technique was applied, using a computer-assisted electrocardiograph, to 10 healthy volunteers (6 high and 4 low hypnotizable subjects as determined by the Stanford Hypnotic Susceptibility Scale, Form C) in randomized awake and neutral hypnosis conditions. Preliminary results indicated that hypnosis affects heart rate variability, shifting the balance of the sympatho-vagal interaction toward an enhanced parasympathetic activity, concomitant with a reduction of the sympathetic tone. A positive correlation between hypnotic susceptibility and autonomic responsiveness during hypnosis was also found, with high hypnotizable subjects showing a trend toward a greater increase of vagal efferent activity than did low hypnotizables.

The dynamic healing process of idiopathic macular holes after surgical repair: a spectral-domain optical coherence tomography study.

PURPOSE To analyze progressive changes of the outer retina after vitrectomy for macular hole (MH) repair. METHODS Nineteen consecutive patients underwent vitrectomy for idiopathic MH. Spectral domain optical coherence tomography (SD-OCT) examinations were performed pre- and postoperatively during follow-up visits at 1, 3, 6, 9, and 12 months. Active eye-tracking technology ensured that the same scanning location was identified each time. RESULTS Ten eyes showed a normal external limiting membrane (ELM) at 1 month after surgery and 15 eyes at 3 months. The ELM was already continuous in 79% of the eyes with persistent outer foveal defects during follow-up. No eyes revealed a continuous inner segment/outer segment (IS/OS) line at 1 month, only one eye at 3 months, and 10 eyes at 12 months. No eyes had a disrupted ELM with an intact IS/OS line. Foveal cysts were visible in three eyes at 1 month and in eight eyes during follow-up. The cystic space gradually filled, resulting in a continuous IS/OS line in five of these eyes. Recovery of ELM, IS/OS, and outer nuclear layer (ONL) determined most of visual acuity improvement. The ONL appeared normal in the 10 eyes with an intact IS/OS line at last follow-up. By contrast, it was disrupted in 7 of 9 eyes with a final persistent outer foveal defect. CONCLUSIONS The ELM is the first structure to recover after MH closure. Foveal cysts may develop during follow-up, and in the presence of an intact ONL, they may gradually fill with complete recovery of the IS/OS junction.

Artifacts in automatic retinal segmentation using different optical coherence tomography instruments.

Purpose: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. Methods: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 &mgr;m) versus noncentral location of errors were studied. Results: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P ≤ 0.005) except the Optovue RTvue-100 (P = 0.165). Conclusion: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability.

Spectral-Domain Optical Coherence Tomography as an Indicator of Fluorescein Angiography Leakage from Choroidal Neovascularization

PURPOSE To evaluate spectral-domain optical coherence tomography (SD-OCT) findings that predict angiographic leakage in choroidal neovascularization (CNV). METHODS SD-OCT and fluorescein angiography (FA) images of 93 eyes of 93 patients were retrospectively analyzed. All patients were previously treated with anti-vascular endothelial growth factor agents for CNV from age-related macular degeneration. FA images were analyzed to assess the presence of leakage. SD-OCT images were analyzed to identify the overall presence of fluid, as well as specific patterns of fluid presentation, including intraretinal cystic spaces (ICS), retinal pigment epithelium detachment (PED), and neurosensory detachment (NSD). The presence of ultrastructural features such as intraretinal hyperreflective flecks and the inherent reflectivity and boundary definition of the subretinal material were evaluated. Both the association and the sensitivity, specificity, and both positive and negative predictive values of SD-OCT findings compared with FA leakage were calculated. RESULTS A statistically significant association between SD-OCT findings and FA leakage was found for eyes that displayed fluid, NSD, intraretinal flecks, and low reflectivity or undefined boundaries from subretinal material, and not for PED or ICS. Sensitivity and specificity for SD-OCT findings were, respectively: 94% and 27% for fluid; 68% and 88% for NSD; 81% and 83% for intraretinal flecks; 63% and 92% for undefined boundaries of subretinal material; and 94% and 87% for low reflectivity from subretinal material. CONCLUSIONS The evidence of fluid on SD-OCT is sensitive but nonspecific in identifying FA leaky CNV. The assessment of neurosensory detachment as well as other ultrastructural elements may increase the specificity of analysis.

Choroidal granulomas visualized by enhanced depth imaging optical coherence tomography.

Purpose: To assess the visualization of choroidal granulomas (CG) by enhanced depth imaging optical coherence tomography (EDI-OCT) and to describe their EDI-OCT characteristics. Methods: Combined indocyanine green (ICG) angiography and EDI-OCT images of 44 CG (sarcoid, tubercular, or Vogt–Koyanagi–Harada related) were reviewed. By ICG angiography, CG were classified as full thickness or partial thickness and as small or large. Two independent operators evaluated EDI-OCT scans over granulomas to record their characteristics (full thickness/partial thickness, shape, reflectivity, internal pattern, margins, and shadowing/increased transmission effect). The agreement between ICG angiography and EDI-OCT, the interobserver agreement, and the correlations between EDI-OCT features and lesion size or disease were studied. Results: Enhanced depth imaging optical coherence tomography could visualize 100% of CG detected on ICG. Lesions resulted full thickness in 90.9% and 77.3% of the cases on ICG angiography and EDI-OCT, respectively (K = 0.5). All CG were more homogeneous and showed increased transmission of the optical coherence tomography signal as compared with the surrounding choroid. Choroidal granulomas angiographic size influenced lesions characteristics on EDI-OCT. Large granulomas were more likely to be full thickness, round shaped, with defined margins, lower reflective than the surrounding structures, and with internal homogenous pattern. The type of disease significantly influenced CG shape and pattern. Most of tubercular-related lesions showed lobulated shape and nonhomogeneous internal pattern. Conclusion: Enhanced depth imaging optical coherence tomography is suitable to visualize CG and to describe their characteristics. Choroidal granulomas size and disease influence lesions appearance on EDI-OCT. Increased transmission effect could be helpful for CG identification.

Surgical removal of subfoveal choroidal neovascular membranes in high myopia

Abstract · Background: A study was carried out to elucidate the anatomical and functional outcome after surgical excision of subfoveal choroidal neovascular membranes in high myopia. · Methods: Sixty-five patients with high myopia (≥6 diopters), well-defined subfoveal neovascular membranes on fluorescein angiography and preoperative visual acuity ≤20/100 were selected for surgery. A standardized surgical technique was used in all cases, by a single surgeon. The main outcomes assessed were Snellen visual acuity, surgical retinal pigment epithelium defect and postoperative perfusion of the choriocapillaris. Multifactor analysis of variance and chi-square/Fisher’s exact test statistics were used to assess the association between patients’ pre- and postoperative characteristics and outcome measures. · Results: Follow-up ranged from 6 to 48 months (mean 16 months). Mean postoperative visual acuity (0.18) was significantly better than mean preoperative visual acuity (0.09). Visual acuity improved by at least two lines in 29 eyes (45%) and was unchanged in 24 (37%). Overall, 43 eyes (66%) had visual acuity of 20/200 or better and 15 (23%), 20/60 or better. Predictive factors with a significant effect on final visual acuity were mean visual acuity, preoperative status of retinal pigment epithelium and postoperative perfusion of the choriocapillaris. Postoperative perfusion was detected in 31 (48%) of the total 65 eyes and in 12 (67%) of the 18 eyes with normal retinal pigment epithelium at baseline. The mean postoperative retinal pigment epithelium defect was 4.6 times larger than the original neovascular membrane. In selected patients, SLO macular scotometry showed areas of retained retinal sensitivity within the atrophic scar. · Conclusion: The natural history of subfoveal neovascularization in high myopia is rarely visually restorative. By contrast, surgical excision of the membranes is feasible and may restore visual acuity in selected patients. This therapeutic approach merits a formal multicenter clinical trial.

Diagnosis of macular pseudoholes and lamellar macular holes: is optical coherence tomography the “gold standard”?

Aim: To assess fundus autofluorescence (AF) for differential diagnosis of macular pseudoholes (MPH) and lamellar macular holes (LMH) evaluated by optical coherence tomography (OCT) as the “gold standard”. Methods: The files on 50 eyes of 46 consecutive patients diagnosed by OCT as having a foveal defect with residual retinal tissue at the bottom were reviewed. Retinal thickness was measured at the foveal centre and 750 μm temporally and nasally to differentiate further MPH and LMH. The corresponding corrected AF images were then evaluated. Eyes with either macular pucker or stage 1a impending macular hole served as controls. Results: OCT measurements allowed the classification of two different profiles: 28 eyes classified with MPH had macular centres and perifoveal retinas that were significantly thicker than the 22 eyes classified with LMH. The corrected value of the foveal AF intensity was not significantly different between the two groups. In addition, the AF did not correlate with the thickness of the retinal tissue at the base of either MPH or LMH eyes. None of the control eyes showed foveal AF. Conclusions: The findings suggest that OCT data must be interpreted with caution when differentiating between MPH and LMH. In this series, the two groups showed similar foveal AF. AF imaging may add useful information to the differential diagnosis of MPH from LMH: the presence of foveal AF is consistent with a loss of foveal tissue and therefore a diagnosis of LMH.

Displayed reflectivity of choroidal neovascular membranes by optical coherence tomography correlates with presence of leakage by fluorescein angiography.

Purpose: To evaluate and correlate the displayed optical reflectivity of choroidal neovascularization (CNV) subretinal material on spectral-domain optical coherence tomography with the presence of dye leakage on fluorescein angiography (FA). Methods: Thirty-nine eyes of 39 patients with a diagnosis of predominantly classic CNV from age-related macular degeneration underwent simultaneous spectral-domain optical coherence tomography and FA imaging. Eight patients had a newly diagnosed untreated CNV. Thirty-one patients had already been treated with anti-vascular endothelial growth factor agents. In 18 of these eyes, CNV lesions showed persistent leakage on FA. In 13 eyes, CNV lesions did not show leakage by FA. Subretinal CNV material boundaries visualized on spectral-domain optical coherence tomography B-scans were manually traced, and optical reflectivity was calculated using the mean grayscale value. To account for variable image brightness, the retinal pigment epithelial reflectivity was measured. The absolute difference between CNV material and retinal pigment epithelial reflectivity (ΔREF) from the three groups (newly diagnosed CNV, previously treated CNV showing FA leakage, and previously treated CNV not showing FA leakage) was compared. Results: In untreated lesions, ΔREF was significantly higher compared with previously treated, but still leaky CNV (P < 0.0001). Lesions showing FA leakage had significantly higher ΔREF compared with those that did not display leakage (P < 0.0001). Conclusion: The displayed reflectivity of subretinal CNV material in spectral-domain optical coherence tomography appears to be an important parameter that can provide information regarding the FA leakage status.

Aligning scan locations from consecutive spectral-domain optical coherence tomography examinations: a comparison among different strategies.

PURPOSE We compared intrasession repeatability values produced by different spectral-domain optical coherence tomography (SD-OCT) instruments when measuring macular retinal thickness from consecutive examinations. METHODS A total of 40 eyes from 23 healthy subjects and 47 eyes from 42 patients with macular edema were enrolled in the study. Subjects underwent two consecutive SD-OCT examinations using three instruments: spectralis HRA+OCT, Cirrus, and RS 3000. For the second SD-OCT examination, the scan location was aligned to the baseline exam using different strategies: RS 3000 eye-tracking (pre-acquisition), Spectralis follow-up (during acquisition), Cirrus fovea finding (postacquisition), and Cirrus macular change analysis (postacquisition). Macular retinal thickness values from the consecutive examinations were evaluated to assess repeatability of the measurements. RESULTS In healthy subjects all of the strategies used for scan location alignment for the second examination provided good repeatability. For instance, intraclass correlation coefficients (ICC) from the central subfield were between 0.88 (RS 3000 eye-tracking) and 0.99 (Spectralis follow-up). In subjects affected by macular edema, the results were excellent. Cirrus macular change analysis and Spectralis follow-up produced ICC values equaled 1.00 in the central subfield. Cirrus fovea finding and RS 3000 eye-tracking produced slightly lower ICC values (0.98 and 0.99, respectively) in the central subfield. CONCLUSIONS All of the strategies for aligning consecutive SD-OCT scan locations produced repeatable retinal thickness values. The best results were obtained using the Spectralis with follow-up and Cirrus with macular change analysis.