Giulio Barteselli

Choroidal Volume Variations with Age, Axial Length, and Sex in Healthy Subjects: A Three-Dimensional Analysis

PURPOSE To demonstrate the 3-dimensional choroidal volume distribution in healthy subjects using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with age, sex, and axial length. DESIGN Retrospective case series. PARTICIPANTS A total of 176 eyes from 114 subjects with no retinal or choroidal disease. METHODS The EDI SD-OCT imaging studies of healthy patients who had undergone a 31-raster scanning protocol on a commercial SD-OCT device were reviewed. Manual segmentation of the choroid was performed by 2 retinal specialists. A macular choroidal volume map and 3-dimensional topography were automatically created by the built-in software of the device. Mean choroidal volume was calculated for each Early Treatment Diabetic Retinopathy Study (ETDRS) subfield. Regression analyses were used to evaluate the correlation between macular choroidal volume and age, sex, and axial length. MAIN OUTCOME MEASURES Three-dimensional topography and ETDRS-style volume map of the choroid. RESULTS Three-dimensional topography of the choroid and volume map was obtained in all cases. The mean choroidal volume was 0.228 ± 0.077 mm(3) for the center ring and 7.374 ± 2.181 mm(3) for the total ETDRS grid. The nasal quadrant showed the lowest choroidal volume, and the superior quadrant showed the highest choroidal volume. The temporal and inferior quadrants did not show different choroidal volume values. Choroidal volume in all the EDTRS rings was significantly correlated with axial length after adjustment for age (P < 0.0001), age after adjustment for axial length (P < 0.0001), and sex after adjustment for axial length (P < 0.05). Choroidal volume decreases by 0.54 mm(3) (7.32%) for every decade and by 0.56 mm(3) (7.59%) for every millimeter of axial length. Male subjects have a 7.37% greater choroidal volume compared with that of female subjects. CONCLUSIONS Enhanced depth imaging SD-OCT is a noninvasive and well-tolerated procedure with an excellent ability to visualize 3-dimensional topography of the choroid and to measure choroidal volume at the posterior pole using manual segmentation. Age and axial length are inversely correlated with choroidal volume, most likely leading to changes in retinal metabolic support in elderly, highly myopic patients. Sexual differences should be considered when interpreting an EDI SD-OCT scan of the choroid. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Repeatability and Reproducibility of Manual Choroidal Volume Measurements Using Enhanced Depth Imaging Optical Coherence Tomography

PURPOSE To evaluate the repeatability and reproducibility of manual choroidal volume (CV) measurements by spectral domain- optical coherence tomography (SD-OCT) using enhanced depth imaging (EDI). METHODS Sixty eyes of 32 patients with or without any ocular chorioretinal diseases were enrolled prospectively. Thirty-one choroidal scans were performed on each eye, centered at the fovea, using a raster protocol. Two masked observers demarcated choroidal boundaries by using built-in automated retinal segmentation software on two separate sessions. Observers were masked to each others and their own previous readings. A standardized grid centered on the fovea was positioned automatically by OCT software, and values for average CVs and total CVs in three concentric rings were noted. The agreement between the intraobserver measurements or interobserver measurements was assessed using the concordance correlation coefficient (CCC). Bland-Altman plots were used to assess the clinically relevant magnitude of differences between inter- and intraobserver measurements. RESULTS The interobserver CCC for the overall average CV was very high, 0.9956 (95% confidence interval [CI], 0.991-0.9968). CCCs for all three Early Treatment Diabetic Retinopathy Study concentric rings between two graders was 0.98 to 0.99 (95% CI, 0.97-0.98). Similarly intraobserver repeatability of two graders also ranged from 0.98 to 0.99. The interobserver coefficient of reproducibility was approximately 0.42 (95% CI, 0.34-0.5 mm(3)) for the average CV. CONCLUSIONS CV measurement by manual segmentation using built-in automated retinal segmentation software on EDI-SD-OCT is highly reproducible and repeatable and has a very small range of variability.

Neurodegeneration in Type 2 Diabetes: Evidence From Spectral-Domain Optical Coherence Tomography

PURPOSE The purpose of this study was to assess changes in the neural retina in eyes with different stages of diabetic retinopathy (DR) in comparison to age-matched healthy subjects. METHODS Retrospective analysis of spectral-domain optical coherence tomography (SD-OCT) scans of 76 naïve eyes of 62 subjects with diabetes was performed. Key exclusion criteria included presence of diabetic macular edema, any other retinal disease, history of any treatment for DR, or incorrect segmentation of the retinal layers on SD-OCT scans. Eyes from diabetic patients were divided into three groups, including no DR, nonproliferative DR (NPDR), and proliferative DR (PDR). A control group of 67 eyes of 66 age-matched healthy volunteers was included for comparison. Average, minimum, and sectoral thicknesses for the ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) were collected from both groups and compared using an ANOVA test. RESULTS Among the 76 included eyes, 43 had NPDR, 13 had PDR, and 20 had no signs of DR. Average and minimum GCIPL showed significant thinning in diabetic subjects compared with controls in all stages of DR (P < 0.05), especially involving the papillo-macula bundle. However, GCIPL thickness was similar between diabetic groups. There was no significant difference in average or sectoral RNFL thicknesses among groups; however, the minimum RNFL thickness was lower in diabetics compared with controls (P < 0.05). No relationship between GCIPL and RNFL thicknesses and duration of diabetes was present. CONCLUSIONS Early thinning on the inner retina happens in type 2 diabetes, even before visible vascular signs of DR. This supports the presence of a neurodegenerative process in eyes of patients with diabetes and warrants neuroprotective intervention to prevent chronic neurodegeneration. The SD-OCT may represent an indispensable tool for identifying early signs of neurodegeneration in diabetic patients.

One-Year Outcomes of Aflibercept in Recurrent or Persistent Neovascular Age-Related Macular Degeneration

PURPOSE To evaluate 6-month and 1-year outcomes of every-8-weeks (Q8W) aflibercept in patients with resistant neovascular age-related macular degeneration (AMD). DESIGN Retrospective, interventional, consecutive case series. METHODS Retrospective review of patients with resistance (multiple recurrences or persistent exudation) to every-4-weeks (Q4W) ranibizumab or bevacizumab that were switched to Q8W aflibercept. RESULTS Sixty-three eyes of 58 patients had a median of 13 (interquartile range [IQR], 7-22) previous anti-vascular endothelial growth factor (anti-VEGF) injections. At 6 months after changing to aflibercept, 60.3% of eyes were completely dry, which was maintained up to 1 year. The median maximum retinal thickness improved from 355 μm to 269 μm at 6 months (P < .0001) and 248 μm at 1 year (P < .0001). There was no significant improvement in ETDRS visual acuity at 6 months (P = .2559) and 1 year follow-up (P = .1081) compared with baseline. The mean difference in ETDRS visual acuity compared to baseline at 6 months was -0.05 logMAR (+2.5 letters) and 0.04 logMAR at 1 year (-2 letters). CONCLUSION Sixty percent of eyes with resistant AMD while on Q4W ranibizumab or bevacizumab were completely dry after changing to Q8W aflibercept at the 6-month and 1-year follow-ups, but visual acuity did not significantly improve. Only a third of eyes needed to be switched from Q8W to Q4W aflibercept owing to persistence of fluid; Q8W dosing of aflibercept without the initial 3 monthly loading doses may be a good alternative in a select group of patients who may have developed ranibizumab or bevacizumab resistance.

Choroidal Findings in Dome-Shaped Macula in Highly Myopic Eyes: A Longitudinal Study

PURPOSE To describe choroidal findings in dome-shaped macula associated with high myopia using fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD OCT), and to elucidate the mechanism and natural course of serous retinal detachment (RD) associated with dome-shaped macula. DESIGN Retrospective, observational case series. METHODS We reviewed longitudinal imaging results of 52 highly myopic eyes with dome-shaped macula. Changes on FA and ICGA were assessed. Retinal, choroidal, and scleral thicknesses and bulge height were measured on SD OCT. RESULTS Serous RD was the most common abnormality associated with dome-shaped macula, detected by SD OCT in 44% of the cases with no associated choroidal neovascularization. Significant differences in the proportion of eyes with pinpoint leakage on FA (P < .001), punctate hypercyanescence on ICGA (P < .001), and pigment epithelium detachment on SD OCT (P < .001) were noted inside the inward bulge of the staphyloma between eyes with and without serous RD. Serous RD was not associated with hyperpermeability areas on ICGA. Eyes with serous RD had thicker choroid (P = .004) and tended to have thicker sclera (P = .067) and greater bulge height (P = .079). Choroidal thickness, scleral thickness, and bulge height were positively correlated (P < .01). All eyes presented a fluctuating course of serous RD during follow-up. Worsening of serous RD was associated with appearance of new punctate hypercyanescent spots on ICGA and leaking points on FA (P < .001 and P = .016, respectively). CONCLUSION Serous RD in dome-shaped macula was likely caused by choroidal vascular changes, similar to central serous chorioretinopathy, but specifically confined in the inward bulge of the staphyloma and secondary to excessive scleral thickening. Serous retinal detachment showed fluctuating changes over time, with alternating active and inactive stages. Angiographic findings in dome-shaped macula suggest the choroid as a target for possible treatment strategies.

Accuracy of the Heidelberg Spectralis in the alignment between near-infrared image and tomographic scan in a model eye: a multicenter study

PURPOSE To evaluate temporal changes and predictors of accuracy in the alignment between simultaneous near-infrared image and optical coherence tomography (OCT) scan on the Heidelberg Spectralis using a model eye. DESIGN Laboratory investigation. METHODS After calibrating the device, 6 sites performed weekly testing of the alignment for 12 weeks using a model eye. The maximum error was compared with multiple variables to evaluate predictors of inaccurate alignment. Variables included the number of weekly scanned patients, total number of OCT scans and B-scans performed, room temperature and its variation, and working time of the scanning laser. A 4-week extension study was subsequently performed to analyze short-term changes in the alignment. RESULTS The average maximum error in the alignment was 15 ± 6 μm; the greatest error was 35 μm. The error increased significantly at week 1 (P = .01), specifically after the second imaging study (P < .05); reached a maximum after the eighth patient (P < .001); and then varied randomly over time. Predictors for inaccurate alignment were temperature variation and scans per patient (P < .001). For each 1 unit of increase in temperature variation, the estimated increase in maximum error was 1.26 μm. For the average number of scans per patient, each increase of 1 unit increased the error by 0.34 μm. CONCLUSION Overall, the accuracy of the Heidelberg Spectralis was excellent. The greatest error happened in the first week after calibration, and specifically after the second imaging study. To improve the accuracy, room temperature should be kept stable and unnecessary scans should be avoided. The alignment of the device does not need to be checked on a regular basis in the clinical setting, but it should be checked after every other patient for more precise research purposes.

Abnormal Fundus Autofluorescence Results of Patients in Long-term Treatment with Deferoxamine

PURPOSE To describe and classify patterns of abnormal fundus autofluorescence (FAF) of patients with β-thalassemia receiving long-term treatment with deferoxamine (DFO). DESIGN Prospective, cross-sectional, case-control study. PARTICIPANTS A total of 197 consecutive patients with β-thalassemia major or intermedia with at least 10 years of treatment with DFO were recruited in a tertiary referral center in Milan, Italy, and were investigated. Seventy-nine thalassemic patients without a history of chelation therapy were included as a control group. METHODS All of the patients were investigated using best-corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal scanning laser ophthalmoscopy (cSLO) and were compared with the control group. MAIN OUTCOME MEASURES Identification of abnormal FAF patterns in thalassemic patients treated with long-term DFO and their progression and relationship with visual function. RESULTS Abnormal FAF not related to other diseases was observed in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns: minimal change, focal, patchy, and speckled. The abnormal increased or decreased FAF was bilateral in all the cases, and only in some cases did it correspond to funduscopically visible alterations. There were no FAF abnormalities in the control group. During the follow-up, progressive FAF changes related to retinal pigment epithelium (RPE) damage occurred in the patchy pattern, associated with decreasing BCVA. Patients with speckled and focal patterns showed limited or no changes in FAF during the follow-up. No changes in FAF were found in patients with a minimal change pattern. No treated patient with a normal baseline examination demonstrated FAF changes. Patients with patterns other than the minimal change showed significant BCVA deterioration (P<0.001). CONCLUSIONS Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring the status of the macula in patients at risk of DFO toxicity. It may be useful in the decision to discontinue or switch the therapy in cases of particular high risk for disease progression. The progressive alteration of the RPE suggests an important role of pathologic RPE changes in the evolution of visual loss during long-term treatment with DFO.

Choroidal volume variations during childhood.

PURPOSE We analyzed choroidal volume (CV) variations during childhood using enhanced depth imaging optical coherence tomography, and evaluated its association with age, axial length (AXL), sex, weight, and height. METHODS Imaging studies of the right eyes of 52 healthy children were reviewed and included in this study. Subjects underwent a complete ocular examination and AXL measurement, as well as a raster macular scan using the Heidelberg Spectralis device. The choroid was segmented manually. RESULTS Subjects included 21 males and 31 females, with mean age of 9 years (range, 2-17 years) and mean AXL of 22.8 ± 0.98 mm. Mean CV was 0.263 ± 0.068 mm(3) for the foveal circle and 8.545 ± 1.822 mm(3) for the total Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. The CV of the nasal quadrant was significantly lower than all others (P < 0.001). Total and foveal CV showed significant negative correlation with AXL after adjustment for age (P < 0.001), and significant positive correlation with age after adjustment for AXL (P < 0.001). Total CV was correlated significantly with sex after adjusting for AXL (P = 0.01), while no correlations were found between total CV and height or weight. The CV increased by 0.214 mm(3) (2.5%) for every year, and decreased by 1.0 mm(3) (11.7%) for every millimeter of axial length. Regression analysis confirmed a trend of higher CV in females than in males (P = 0.056). CONCLUSIONS The CV increases with age during childhood, but decreases with AXL. This finding supports the hypothesis that the choroid grows progressively during childhood. Intersexual differences of CV also may be present.

Characterization of Microaneurysm Closure After Focal Laser Photocoagulation in Diabetic Macular Edema

PURPOSE To characterize microaneurysm closure following focal laser photocoagulation in diabetic macular edema (DME) using simultaneous fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). DESIGN Retrospective observational case series. METHODS Leaking microaneurysms (n = 123) were analyzed in eyes (n = 29) with nonproliferative diabetic retinopathy (NPDR) that underwent navigated focal laser photocoagulation in DME and were followed at 3, 6, and 12 months. Closure of diabetic microaneurysms was characterized in detail following focal laser using SD-OCT. RESULTS Closure rate of microaneurysms by both FA and SD-OCT was 69.9% (84/123), 79.7% (98/123), and 82.9% (102/123) at 3, 6, and 12 months, respectively. Microaneurysm closure rate increased at 6 and 12 months compared to 3 months (P < .003, P < .001). Over half of closed microaneurysms (45/86, 52.3%) left hyperreflective spots while the remaining half (41/86, 47.7%) disappeared without any hyperreflectivity by SD-OCT at 3 months. Hyperreflective spots decreased at 6 (36/99, 36.4%) and 12 months (17/102, 16.7%) with a concomitant increase in complete loss of reflectivity at 6 (63/99, 63.6%) and 12 months (85/102, 83.3%). Smaller outer and inner diameters and heterogeneous lumen reflectivity were positively associated with microaneurysm closure at 12 months (P < .0001, P < .001, P < .03). CONCLUSIONS Characterization of microaneurysms following focal laser photocoagulation resulted in hyperreflective spots and complete resolution of all reflectivity using SD-OCT. Smaller microaneurysms and those with heterogeneous lumen were positively associated with microaneurysm closure. These findings provide greater understanding of localized retinal changes following focal laser photocoagulation in DME treatment.

Visual Function Assessment in Simulated Real-Life Situations in HIV-Infected Subjects

Visual function abnormalities are common in people living with HIV disease (PLWH) without retinitis, even after improvement in immune status. Abnormalities such as reduced contrast sensitivity, altered color vision, peripheral visual field loss, and electrophysiological changes are related to a combination of retinal dysfunctions, involving inner and outer retinal structures. The standard protocol for testing vision performance in clinical practice is the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. However, this method poorly correlates with activities of daily living that require patients to assess visual stimuli in multiple light/contrast conditions, and with limited time. We utilized a novel interactive computer program (Central Vision Analyzer) to analyze vision performance in PLWH under a variety of light/contrast conditions that simulate stressful and real-world environments. The program tests vision in a time-dependent way that we believe better correlates with daily living activities than the non-timed ETDRS chart. We also aimed to correlate visual scores with retinal neuro-fiber layer thickness on optical coherence tomography. Here we show that visual acuity is more affected in PLWH in comparison to HIV-seronegative controls in varying contrast and luminance, especially if the nadir CD4+ T-cell count was lower than 100 cells/mm3. Visual impairment reflects the loss of retinal nerve fiber layer thickness especially of the temporal-inferior sector. In PLWH the ETDRS chart test led to better visual acuity compared to the Central Vision Analyzer equivalent test, likely because patients had indefinite time to guess the letters. This study confirms and strengthens the finding that visual function is affected in PLWH even in absence of retinitis, since we found that the HIV serostatus is the best predictor of visual loss. The Central Vision Analyzer may be useful in the diagnosis of subclinical HIV-associated visual loss in multiple light/contrast conditions, and may offer better understanding of this entity called “neuroretinal disorder”.