Carmen A. Puliafito

Imaging of Macular Diseases with Optical Coherence Tomography

BACKGROUND/PURPOSE To assess the potential of a new diagnostic technique called optical coherence tomography for imaging macular disease. Optical coherence tomography is a novel noninvasive, noncontact imaging modality which produces high depth resolution (10 microns) cross-sectional tomographs of ocular tissue. It is analogous to ultrasound, except that optical rather than acoustic reflectivity is measured. METHODS Optical coherence tomography images of the macula were obtained in 51 eyes of 44 patients with selected macular diseases. Imaging is performed in a manner compatible with slit-lamp indirect biomicroscopy so that high-resolution optical tomography may be accomplished simultaneously with normal ophthalmic examination. The time-of-flight delay of light backscattered from different layers in the retina is determined using low-coherence interferometry. Cross-sectional tomographs of the retina profiling optical reflectivity versus distance into the tissue are obtained in 2.5 seconds and with a longitudinal resolution of 10 microns. RESULTS Correlation of fundus examination and fluorescein angiography with optical coherence tomography tomographs was demonstrated in 12 eyes with the following pathologies: full- and partial-thickness macular hole, epiretinal membrane, macular edema, intraretinal exudate, idiopathic central serous chorioretinopathy, and detachments of the pigment epithelium and neurosensory retina. CONCLUSION Optical coherence tomography is potentially a powerful tool for detecting and monitoring a variety of macular diseases, including macular edema, macular holes, and detachments of the neurosensory retina and pigment epithelium.

Intravitreal triamcinolone for refractory diabetic macular edema

PURPOSE To determine if intravitreal injection of triamcinolone acetonide is safe and effective in treating diabetic macular edema unresponsive to prior laser photocoagulation. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Sixteen eyes with clinically significant diabetic macular edema (CSME) that failed to respond to at least two previous sessions of laser photocoagulation. METHODS Eyes were diagnosed with CSME and treated with at least two sessions of laser photocoagulation according to Early Treatment Diabetic Retinopathy Study guidelines. At least 6 months after initial laser therapy, the response was measured by clinical examination and optical coherence tomography (OCT). Eyes with a residual central macular thickness of more than 300 microm (normal, 200 microm) and visual loss from baseline were offered intravitreal injection of 4 mg triamcinolone acetonide. The visual and anatomic responses were observed as well as complications related to the injection procedure and corticosteroid medication. MAIN OUTCOME MEASURES Visual acuity and quantitative change in OCT macular thickening were assessed. Potential complications were monitored, including intraocular pressure response, cataract progression, retinal detachment, vitreous hemorrhage, and endophthalmitis. RESULTS All patients completed 3 months of follow-up, and 8 of 16 patients (50%) completed 6 or more months of follow-up. Mean improvement in visual acuity measured 2.4, 2.4, and 1.3 Snellen lines at the 1-, 3-, and 6-month follow-up intervals, respectively. The central macular thickness as measured by OCT decreased by 55%, 57.5%, and 38%, respectively, over these same intervals from an initial pretreatment mean of 540.3 microm (+/-96.3 microm). Intraocular pressure exceeded 21 mmHg in 5, 3, and 1 eye(s), respectively, during these intervals. One eye exhibited cataract progression at 6 months. No other complications were noted over a mean follow-up of 6.2 months. Reinjection was performed in 3 of 8 eyes after 6 months because of recurrence of macular edema. CONCLUSIONS Intravitreal triamcinolone is a promising therapeutic method for diabetic macular edema that fails to respond to conventional laser photocoagulation. Complications do not appear to be prohibitive. Further study is warranted to assess the long-term efficacy and safety, and the need for retreatment.

Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration.

To determine whether intravitreal bevacizumab could improve optical coherence tomography and visual acuity outcomes in a patient with neovascular age-related macular degeneration who was responding poorly to pegaptanib therapy, an intravitreal injection of bevacizumab (1.0 mg) was given. Within 1 week, optical coherence tomography revealed resolution of the subretinal fluid, resulting in a normal-appearing macular contour. The improved macular appearance was maintained for at least 4 weeks, and visual acuity remained stable. No inflammation was observed. An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age-related macular degeneration who are losing vision secondary to macular neovascularization.

In vivo retinal imaging by optical coherence tomography

We describe what are to our knowledge the first in vivo measurements of human retinal structure with optical coherence tomography. These images represent the highest depth resolution in vivo retinal images to date. The tomographic system, image-processing techniques, and examples of high-resolution tomographs and their clinical relevance are discussed.

Topography of Diabetic Macular Edema with Optical Coherence Tomography

OBJECTIVE This study aimed to develop a protocol to screen and monitor patients with diabetic macular thickening using optical coherence tomography (OCT), a technique for high-resolution cross-sectional imaging of the retina. DESIGN A cross-sectional pilot study was conducted. PARTICIPANTS A total of 182 eyes of 107 patients with diabetic retinopathy, 55 eyes from 31 patients with diabetes but no ophthalmoscopic evidence of retinopathy, and 73 eyes from 41 healthy volunteers were studied. INTERVENTION Six optical coherence tomograms were obtained in a radial spoke pattern centered on the fovea. Retinal thickness was computed automatically from each tomogram at a total of 600 locations throughout the macula. Macular thickness was displayed geographically as a false-color topographic map and was reported numerically as averages in each of nine regions. MAIN OUTCOME MEASURES Correlation of OCT with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity was measured. RESULTS Optical coherence tomography was able to quantify the development and resolution of both foveal and extrafoveal macular thickening. The mean +/- standard deviation foveal thickness was 174 +/- 18 microns in normal eyes, 179 +/- 17 microns in diabetic eyes without retinopathy, and 256 +/- 114 microns in eyes with nonproliferative diabetic retinopathy. Foveal thickness was highly correlated among left and right eyes of normal eyes (mean +/- standard deviation difference of 6 +/- 9 microns). Foveal thickness measured by OCT correlated with visual acuity (r2 = 0.79). A single diabetic eye with no slit-lamp evidence of retinopathy showed abnormal foveal thickening on OCT. CONCLUSIONS Optical coherence tomography was a useful technique for quantifying macular thickness in patients with diabetic macular edema. The topographic mapping protocol provided geographic information on macular thickness that was intuitive and objective.

Reproducibility of Nerve Fiber Layer Thickness Measurements Using Optical Coherence Tomography

PURPOSE Optical coherence tomography (OCT) is a new technology that uses near-infrared light in an interferometer to produce approximately 10-microns resolution cross-sectional images of the tissue of interest. The authors performed repeated quantitative assessment of nerve fiber layer thickness in individuals with normal and glaucomatous eyes, and they evaluated the reproducibility of these measurements. METHODS The authors studied 21 eyes of 21 subjects by OCT. Each subject underwent five repetitions of a series of scans on five separate occasions within a 1-month period. Each series consisted of three circular scans around the optic nerve head (diameters, 2.9, 3.4, and 4.5 mm). Each series was performed separately using internal (fixation with same eye being studied) and external (fixation with contralateral eye) fixation techniques. The eye studied and the sequence of testing were assigned randomly. RESULTS Internal fixation (IF), in general, provides a slightly higher degree of reproducibility than external fixation (EF). Reproducibility was better in a given eye on a given visit than from visit to visit. Reproducibility as measured by intraclass correlation coefficients were as follows: circle diameter (CD), 2.9 mm, 0.51/0.57 (normal/glaucoma) (IF), 0.43/0.54 (EF); CD, 3.4 mm, 0.56/0.52 (IF), 0.43/0.61 (EF); CD, 4.5 mm, 0.53/0.43 (IF), 0.42/0.49 (EF). CONCLUSIONS Nerve fiber layer thickness can be reproducibly measured using OCT. Internal is superior to external fixation; each circle diameter tested provides adequate reproducibility.

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.

Purpose: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). Methods: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. Results: Fifty–three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P<0.001) and the mean central retinal thickness decreased by 99.6 &mgr;m (P<0.001). Conclusion: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.

Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion.

To determine whether bevacizumab could improve visual acuity and optical coherence tomography outcomes in a patient with macular edema from central retinal vein occlusion, an intravitreal injection of bevacizumab (1.0 mg) was given. Prior intravitreal injections of triamcinolone acetonide resulted in vision improvement but worsening cataract and borderline glaucoma. Within 1 week of the bevacizumab injection, visual acuity improved from 20/200 to 20/50 and optical coherence tomography revealed resolution of the cystic maculopathy. The improvements were maintained for at least 4 weeks. Intravitreal injections of bevacizumab may provide another treatment option for patients with macular edema from vein occlusions.

Optical coherence tomography of age-related macular degeneration and choroidal neovascularization.

OBJECTIVE The authors used optical coherence tomography (OCT), a new technique for cross-sectional imaging of the retina, to morphologically study eyes with nonexudative and exudative age-related macular degeneration (AMD). In patients with untreated exudative AMD, OCT was compared with fluorescein angiography in the identification and classification of choroidal neovascularization (CNV). METHODS Optical coherence tomography imaging is analogous to ultrasound, except that the use of light rather than sound enables higher longitudinal resolution with a noncontact and noninvasive measurement. Optical coherence tomography was performed on 391 patients with the clinical diagnosis of AMD and was compared with conventional clinical examination to establish the cross-sectional morphology of different lesions and to develop a classification scheme for CNV. Optical coherence tomograms and fluorescein angiograms then were reviewed and correlated independently in 90 eyes of 86 patients who had exudative AMD without previous laser treatment. RESULTS Pigmentary changes, soft drusen, and detachments of the neurosensory retina and retinal pigment epithelium all had distinct presentations on OCT. Subretinal and intraretinal fluid caused changes in retinal thickness or elevation that could be quantified directly from the images. Choroidal neovascularization was evident in the tomograms as a thickening and fragmentation of a reflective layer, which corresponded to the retinal pigment epithelium and choriocapillaris. Changes in the reflection from this layer were observed during the progression of neovascularization, and after laser photocoagulation treatment. Classic CNV consistently presented with well-defined boundaries on OCT, whereas occult CNV had a variable cross-sectional appearance. CONCLUSIONS Optical coherence tomography was useful in quantitatively evaluating subretinal and intraretinal fluid, assessing possible subfoveal involvement of neovascularization, and in monitoring CNV before and after laser photocoagulation. Optical coherence tomography was unable to detect CNV beneath serous pigment epithelial detachments. Optical coherence tomography may have potential in accurately defining the boundaries in a subset of angiographically occult CNV.

Automated detection of retinal layer structures on optical coherence tomography images

Segmentation of retinal layers from OCT images is fundamental to diagnose the progress of retinal diseases. In this study we show that the retinal layers can be automatically and/or interactively located with good accuracy with the aid of local coherence information of the retinal structure. OCT images are processed using the ideas of texture analysis by means of the structure tensor combined with complex diffusion filtering. Experimental results indicate that our proposed novel approach has good performance in speckle noise removal, enhancement and segmentation of the various cellular layers of the retina using the STRATUSOCTTM system.