Giovanni Gregori

Simultaneous acquisition of sectional and fundus ophthalmic images with spectral-domain optical coherence tomography.

A high-speed spectral-domain optical coherence tomography (OCT) system was built to image the human retina in vivo. A fundus image similar to the intensity image produced by a scanning laser ophthalmoscope (SLO) was generated from the same spectra that were used for generating the OCT sectional images immediately after the spectra were collected. This function offers perfect spatial registration between the sectional OCT images and the fundus image, which is desired in ophthalmology for monitoring data quality, locating pathology, and increasing reproducibility. This function also offers a practical way to detect eye movements that occur during the acquisition of the OCT image. The system was successfully applied to imaging human retina in vivo.

Progression of Geographic Atrophy in Age-Related Macular Degeneration Imaged with Spectral Domain Optical Coherence Tomography

PURPOSE To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral domain optical coherence tomography (SD-OCT) fundus image. DESIGN Prospective, longitudinal, natural history study. PARTICIPANTS Eighty-six eyes of 64 patients with ≥6 months of follow-up. METHODS Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA). The areas of GA identified on the SD-OCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored. MAIN OUTCOME MEASURES Enlargement rate of GA. RESULTS At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59 mm(2) (1.8 disc areas [DA]). The mean follow-up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square root scale (ICC = 0.996). Intergrader differences were not an important source of variability in lesion size measurement (ICC = 0.999, 0.997). On average, the ER of GA per year was 1.2 mm(2) (0.47 DA; range, 0.01-3.62 mm(2)/year). The ER correlated with the initial area of GA (r = 0.45; P<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the ER (0.28 mm/yr) was not correlated with baseline size (r = -0.09; P = 0.40). In this cohort of lesions, no correlation was found between ER and length of follow-up. Square root transformation of the data helped to facilitate sample size estimates for controlled clinical trials involving GA. CONCLUSIONS The SD-OCT fundus image can be used to visualize and quantify GA. Advantages of this approach include the convenience and assurance of using a single imaging technique that permits simultaneous visualization of GA along with the loss of photoreceptors and the retinal pigment epithelium that should correlate with the loss of visual function.

Photoreceptor Inner/Outer Segment Defect Imaging by Spectral Domain OCT and Visual Prognosis after Macular Hole Surgery

PURPOSE To evaluate photoreceptor inner/outer segment (IS/OS) defect parameters by using spectral domain-optical coherence tomography (SD-OCT) for correlation with visual outcomes in macular hole surgery (MHS). METHODS This study was an interventional, retrospective case series. Twenty-three eyes (23 patients) were examined by SD-OCT before and after (median, 2.3 months) anatomically successful MHS. Two formats of OCT were analyzed: linear (raster) and composite (partial fundus image). Factors that may have confounded IS/OS measurements were controlled by using weighting and normalization of data. The main outcome measures were diameter and area of the IS/OS defect, weighted area of the IS/OS defect, macular density ratio (MDR), healing pattern of the macular hole, and preoperative and postoperative best corrected visual acuity (BCVA). RESULTS Poorer preoperative BCVA correlated with larger preoperative diameter of the IS/OS defect (P = 0.005). A greater improvement in BCVA correlated with a larger preoperative area of IS/OS defect (P = 0.038) and smaller MDR (P = 0.012). Poorer postoperative BCVA correlated with a larger postoperative diameter of the IS/OS defect (P = 0.010), larger weighted postoperative area of IS/OS defect calculated by raster scan (P = 0.013), larger postoperative area of IS/OS defect measured from the partial fundus image (P = 0.003), and apparent glial sealing pattern on SD-OCT (P = 0.0005). The shape of the IS/OS defect area was round and regular before surgery, but irregular afterward. CONCLUSIONS BCVA after MHS correlates with objectively ascertainable SD-OCT measurements of IS/OS defects and other features. The postoperative area of the IS/OS defect, when directly measured, correlates more strongly with BCVA than do linear-based measurements, perhaps because of the irregular shape of the IS/OS defect after surgery.

Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration: The COMPLETE Study

PURPOSE To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). DESIGN Prospective, double-masked, randomized clinical trial. PARTICIPANTS Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging. METHODS Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. MAIN OUTCOME MEASURES Change in area of GA at 26 weeks. RESULTS Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55 ± 0.94 and 2.02 ± 0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19 ± 0.12 and 0.18 ± 0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37 ± 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 ± 0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. CONCLUSIONS Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Swept-source OCT angiography of the retinal vasculature using intensity differentiation-based optical microangiography algorithms.

BACKGROUND AND OBJECTIVE To demonstrate the feasibility of using a 1,050-nm swept-source optical coherence tomography (SS-OCT) system to achieve noninvasive retinal vasculature imaging in human eyes. MATERIALS AND METHODS Volumetric data sets were acquired using a 1-µm SS-OCT prototype that operated at a 100-kHz A-line rate. A scanning protocol designed to allow for motion contrast processing, referred to as OCT angiography or optical microangiography (OMAG), was used to scan an approximately 3 × 3–mm area in the central macular region of the retina within approximately 4.5 seconds. An intensity differentiation-based OMAG algorithm was used to extract three-dimensional retinal functional microvasculature information. RESULTS Intensity signal differentiation generated capillary-level resolution en face OMAG images of the retina. The parafoveal capillaries were clearly visible, thereby allowing visualization of the foveal avascular zone in healthy subjects. CONCLUSION The capability of OMAG to produce retinal vascular images was demonstrated using the 1-µm SS-OCT prototype. This technique has potential clinical value for studying retinal vasculature abnormalities.

Spectral Domain Optical Coherence Tomography Imaging of Drusen in Nonexudative Age-Related Macular Degeneration

PURPOSE To measure drusen area and volume in eyes with nonexudative age-related macular degeneration (AMD) using spectral domain optical coherence tomography imaging (SD-OCT). DESIGN Evaluation of diagnostic technology. PARTICIPANTS One hundred three eyes from 74 patients with drusen. METHODS Patients with drusen secondary to nonexudative AMD were enrolled in this study. Five separate SD-OCT scans, each consisting of 40 000 uniformly spaced A-scans organized as 200 A-scans in each B-scan and 200 horizontal B-scans, were performed on each eye. Each scan covered a retinal area of 6×6 mm centered on the fovea. A novel algorithm was used to quantitatively assess drusen area and volume. Measurements from the entire scans, as well as in regions contained within 3- and 5-mm circles centered on the fovea, were analyzed. Test-retest standard deviations of drusen area and volume measurements were calculated for each eye. MAIN OUTCOME MEASURES Drusen area and volume. RESULTS The algorithm created drusen maps that permitted both qualitative and quantitative assessment of drusen area and volume. Both the qualitative appearance and the quantitative measurements of drusen area and volume were highly reproducible over the 5 different datasets. The intraclass correlation coefficient was >0.99 for both area and volume measurements on the entire dataset as well as the 3- and 5-mm circles. The correlation between lesion size and the test-retest standard deviations can be eliminated by performing a square root transformation of the area measurements and a cube root transformation of the volume measurements. These transformed data allowed for the inclusion of all drusen sizes in the calculation of an estimated single pooled test-retest standard deviation, which will be useful for longitudinal studies of drusen natural history. CONCLUSIONS A novel algorithm for the qualitative and quantitative assessment of drusen imaged using SD-OCT was shown to be highly reproducible. The ability to assess drusen volume reliably represents a new quantitative parameter to measure in AMD and may be useful when assessing disease progression, particularly in trials for treatments of nonexudative AMD.

One-year Safety And Efficacy Of Intravitreal Triamcinolone Acetonide For The Management Of Macular Edema Secondary To Central Retinal Vein Occlusion

Purpose: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (IVTA) as treatment for macular edema associated with central retinal vein occlusion (CRVO). Methods: A retrospective review was performed of data for 40 consecutive patients (40 eyes) with CRVO and macular edema treated with IVTA at the Bascom Palmer Eye Institute (Miami, FL). Results: Median duration of symptoms before the first injection was 3 months (range, 1 day to 8 years). Median Snellen visual acuity was 20/400 at baseline (range, 20/60 to light perception; n = 40), 20/300 at 1 month (P = 0.010; n = 37), 20/300 at 3 months (P = 0.007; n = 33), 20/400 at 6 months (P = 0.726; n = 28), and 8/200 at 1 year (P = 0.569; n = 17). Vision improved by ≥3 lines in 21% of eyes at 1 month, 27% at 3 months, 14% at 6 months, and 12% at 1 year. Visual acuity was unchanged from baseline in 71% of eyes at 6 months and 1 year. By 1 year, 50% of eyes received more than one injection (mean = 1.6 injections; range 1–4 injections). Overall, intraocular pressure increased by ≥10 mmHg in 24% of eyes at 1 year. Trabeculectomy was performed on 2 of 12 eyes with preexisting open-angle glaucoma. Conclusion: IVTA can substantially improve vision in some patients, but most patients have stable visual acuity compared with baseline at 1 year despite repeated injections.

Optical Coherence Tomography Angiography of Asymptomatic Neovascularization in Intermediate Age-Related Macular Degeneration

PURPOSE To determine whether angiography with swept-source (SS) optical coherence tomography (OCT) identifies subclinical type 1 neovascularization in asymptomatic eyes with intermediate age-related macular degeneration (iAMD). DESIGN Prospective, observational, consecutive case series. PARTICIPANTS Patients with asymptomatic iAMD in one eye and neovascular age-related macular degeneration (AMD) in their fellow eye. METHODS The patients underwent SS OCT angiography (OCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA), and the images from these 3 angiographic techniques were compared. MAIN OUTCOME MEASURES Identification of subclinical type 1 neovascularization with SS OCTA in asymptomatic eyes with iAMD. RESULTS Eleven consecutive patients with iAMD in one eye and neovascular AMD in their fellow eye were imaged with FA, ICGA, and SS OCTA between August 2014 and September 2015. Clinical examination of the 11 eyes revealed drusen and pigmentary abnormalities in the central macula and no evidence of macular fluid on routine OCT imaging. Ten of the 11 eyes had no evidence of leakage on FA and 1 eye had questionable fluorescein leakage. Indocyanine green angiography revealed the presence of central macular plaques in 3 of the 11 asymptomatic eyes with iAMD, and SS OCTA revealed unambiguous type 1 neovascularization corresponding to the plaques in all 3 eyes. Optical coherence tomography angiography did not identify neovascularization in the remaining 8 eyes. CONCLUSIONS Swept-source OCTA identified type 1 neovascularization corresponding to ICGA plaques in asymptomatic eyes with iAMD. The ability of OCTA to provide noninvasive, fast, detailed, depth-resolved identification of nonexudative neovascular lesions in eyes with iAMD suggests the need for a new classification system that distinguishes between neovascular and nonneovascular iAMD.

Swept-source OCT angiography of macular telangiectasia type 2.

BACKGROUND AND OBJECTIVE To evaluate the central macular microvascular network in patients with macular telangiectasia type 2 (MacTel2) using optical coherence tomography (OCT)-based microangiography (OMAG). PATIENTS AND METHODS Prospective, observational study of patients with MacTel2 evaluated using a swept-source OCT (SS-OCT) prototype. OMAG was performed using a 3 mm × 3 mm central foveal raster scan. The algorithm segmented the retina into three layers. Microvascular distribution was depicted as en face images, and qualitative information was compared to fluorescein angiography (FA) images. RESULTS OMAG detected abnormal microvasculature in all MacTel2 eyes, predominantly in the middle retinal layers with neovascularization in the outer retina. These vessels correlated well with the FA alterations. The abnormal temporal, juxtafoveal microvasculature in MacTel2 became apparent as the disease progressed and in later stages tended to extend circumferentially, with anastomotic vessels temporally. CONCLUSION OMAG provided detailed, depth- resolved information about the perifoveal macular microvasculature in MacTel2. In most cases, images were better using OMAG than FA. The OMAG images demonstrated that most of the leakage seen on FA appeared to arise from the abnormal perifoveal microvasculature in the middle retinal layer.

Evaluation of Ranibizumab-Induced Changes in High-Resolution Optical Coherence Tomographic Retinal Morphology and Their Impact on Visual Function

PURPOSE To evaluate the effects of intravitreal ranibizumab on retinal function and morphology and to identify a correlation between anatomy and function by using spectral domain optical coherence tomography (SDOCT). METHODS Twenty-three patients affected by neovascular AMD received three injections of ranibizumab in three consecutive months and were monitored by assessment of best corrected visual acuity (BCVA), central retinal sensitivity (CRS) and morphologic changes at the level of the retina and the retinal pigment epithelium (RPE). The morphologic changes, identified by SDOCT segmentation, were mean retinal thickness (MRT), central retinal thickness (CRT), and the pathologic area (lesion area) of the RPE. RESULTS BCVA increased from a mean 60.1 +/- 8.7 letters at baseline to 67.0 +/- 10.9 at month 3 (P = 0.0003). The CRS at the 0 degrees position increased from 2.8 +/- 3.1 dB at baseline to 4.0 +/- 5.7 at week 1, remaining stable until month 3. Absolute scotoma size decreased continuously from baseline to month 3, in a mean of 5.3 +/- 5.8 to 3.6 +/- 4.0 test point locations. By SDOCT, MRT decreased from 308.6 +/- 25.9 microm at baseline to 268.4 +/- 22.4 microm at month 3 (P = 0.0001). CRT was 365.8 +/- 84.9 and 254.9 +/- 95.1 microm at month 3 (P = 0.0002). The mean RPE lesion area was 6.0 +/- 3.0 mm(2) at baseline, which decreased to 5.0 +/- 3.1 mm(2) at month 3 (P = 0.115). The only significant correlation was identified between the lesion area and CRS. CONCLUSIONS In ranibizumab therapy, the condition of the RPE lesion may be more relevant for visual function than the usual OCT parameters, retinal thickness.