Faculty Bibliography

Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.

Previous models of disease in age-related macular degeneration (AMD) were incomplete in that they did not encompass subretinal drusenoid deposits (pseudodrusen), subtypes of neovascularization, and polypoidal choroidal vasculopathy. In addition, Type 3 neovascularization starts in the retina and may not necessarily involve the choroid. As such, the term choroidal neovascularization is not appropriate for these eyes. The new aspects in the AMD construct are to include specific lipoprotein extracellular accumulations, namely drusen and subretinal drusenoid deposits, as early AMD. The deposition of specific types of deposit seems to be highly correlated with choroidal thickness and topographical location in the macula. Late AMD includes macular neovascularization or atrophy. The particular type of extracellular deposit is predictive of the future course of the patient. For example, eyes with subretinal drusenoid deposits have a propensity to develop outer retinal atrophy, complete outer retinal and retinal pigment epithelial atrophy, or Type 3 neovascularization as specific forms of late AMD. Given Type 3 neovascularization may never involve the choroid, the term macular neovascularization is suggested for the entire spectrum of neovascular disease in AMD. In contrast to older classification systems, the proposed system encompasses the relevant presentations of disease and more precisely predicts the future course of the patient. In doing so, the concept was developed that there may be genetic risk alleles, which are not necessarily the same alleles that influence disease expression.

PURPOSE/OBJECTIVE:To investigate the relationship between subfoveal choroidal thickness and disease manifestation in a series of eyes with nonexudative age-related macular degeneration (AMD). METHODS:Retrospective study of eyes with nonexudative AMD. The extracellular deposits present, drusen and subretinal drusenoid deposits (SDD, pseudodrusen) along with a newly recognized form of drusen, pachydrusen, were graded and compared with choroidal thickness as determined by optical coherence tomography. Demographic and imaging information was evaluated with descriptive statistics and generalized estimating equations. RESULTS:There were 94 eyes of 71 patients, who had a mean age of 78.1 years. Soft drusen alone were found in 45 eyes (47.9%) and subretinal drusenoid deposit with or without drusen in 38 (40.4%). Pachydrusen, which were typically larger than 125 μm, often had an irregular outer contour, showed a scattered distribution over the posterior pole and occurred in isolation or in groups of only a few drusen were found in 11 (11.7%). The mean subfoveal choroidal thickness in the soft drusen group was 227.9 μm, in the subretinal drusenoid deposit group 167.3 μm, and in the pachydrusen group 419 μm. The differences between the groups were highly significant. CONCLUSION/CONCLUSIONS:Extracellular deposits, subretinal drusenoid deposits and drusen, which are on either side of the retinal pigment epithelium, respectively, are common in nonexudative AMD. A new form of drusen presentation could be differentiated from typical soft drusen and was associated with thicker choroids. Disease manifestation in nonexudative AMD seems to be associated with choroidal thickness. Each of these has potential to lead to specific forms of late AMD.

PURPOSE/OBJECTIVE:To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). DESIGN/METHODS:Consensus meeting. PARTICIPANTS/METHODS:Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. METHODS:As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. MAIN OUTCOME MEASURES/METHODS:A consensus classification system for atrophy and OCT-based criteria to identify atrophy. RESULTS:OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. CONCLUSIONS:A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

PURPOSE/OBJECTIVE:To examine the alterations in retinal vascular morphology over an extended follow-up in eyes with macular telangiectasis Type 2 (MacTel2). METHODS:Eyes with high-quality digital photographs were evaluated. The geometric distortion in baseline images required to emulate the follow-up images was determined and vectors were made that represented the direction and magnitude of changes, to create a warp field. Optical coherence tomography and optical coherence tomography angiography evaluation of the retina was performed. RESULTS:There were 7 eyes of 4 patients, who had a mean age of 70.25 years, which were followed for a mean of 8.8 years. The eyes showed increasing grayish opacification in the temporal macula with straightening and displacement of the macular vessels, even those in the nasal macula. The warp field vectors pointed to the temporal juxtafoveal macula. There was never any cavitation at the epicenter of the retinal distortion in any patient, although cavitations were found around this area. Optical coherence tomography imaging showed a circumscribed region of hyperreflectivity in the temporal macula. Optical coherence tomography angiography showed a deep angular condensed network of vessels within the hyperreflective region. One eye showed marked atrophic changes including full-thickness macular hole formation, but no increase in graying of the retina, loss of retinal laminations, pigmentary infiltration, or alteration in the retinal vessels. CONCLUSION/CONCLUSIONS:Tissue contraction with retinal vascular displacement and contortion seem to be integral aspects of disease manifestation in MacTel2. The induced vascular changes may lead to secondary effects that increase morbidity in this disease.

PURPOSE/OBJECTIVE:To describe cases presenting with features of idiopathic macular telangiectasia (MacTel) Type 2 and central serous chorioretinopathy (CSC). METHODS:Databases from four tertiary retina centers were searched for cases copresenting CSC and MacTel Type 2. RESULTS:Five cases were identified (4 men, 1 woman; mean age: 67.2 years). Four patients were referred for chronic or nonresolving CSC, and the diagnosis of MacTel Type 2 was made based on multimodal imaging findings. One patient had advanced MacTel Type 2, and developed acute CSC. Regarding the MacTel Type 2 findings, all subjects presented perifoveal telangiectasia on fluorescein angiography, and four subjects showed intraretinal cavitations typical of MacTel Type 2 on optical coherence tomography, in one or both eyes. Regarding the CSC findings, fluorescein angiography identified focal or extended retinal pigment epithelium alteration in all eyes, and an active leakage in two eyes. Indocyanine green angiography showed choroidal vascular hyperpermeability in four subjects. On optical coherence tomography, pigment epithelial detachments were detected in five eyes (four subjects), and foveal detachments were present in five eyes (three subjects), which spontaneously resolved (two eyes), responded to photodynamic therapy (two eyes), or persisted (one eye). Mean choroidal thickness was 402 ± 99 μm. CONCLUSION/CONCLUSIONS:The codiagnosis of CSC and MacTel Type 2 should be considered in atypical presentations associating features from both disorders.

PURPOSE/OBJECTIVE:To investigate the natural history of dot subretinal drusenoid deposits (SDD) in age-related macular degeneration, using high-resolution adaptive optics scanning laser ophthalmoscopy. METHODS:Six eyes of four patients with intermediate age-related macular degeneration were studied at baseline and 1 year later. Individual dot SDD within the central 30° retina were examined with adaptive optics scanning laser ophthalmoscopy and optical coherence tomography. RESULTS:A total of 269 solitary SDD were identified at baseline. Over 12.25 ± 1.18 months, all 35 Stage 1 SDD progressed to advanced stages. Eighteen (60%) Stage 2 lesions progressed to Stage 3 and 12 (40%) remained at Stage 2. Of 204 Stage 3 SDD, 12 (6.4%) disappeared and the rest remained. Twelve new SDD were identified, including 6 (50%) at Stage 1, 2 (16.7%) at Stage 2, and 4 (33.3%) at Stage 3. The mean percentage of the retina affected by dot SDD, measured by the adaptive optics scanning laser ophthalmoscopy, increased in 5/6 eyes (from 2.31% to 5.08% in the most changed eye) and decreased slightly in 1/6 eye (from 10.67% to 10.54%). Dynamism, the absolute value of the areas affected by new and regressed lesions, ranged from 0.7% to 9.3%. CONCLUSION/CONCLUSIONS:Adaptive optics scanning laser ophthalmoscopy reveals that dot SDD, like drusen, are dynamic.

PURPOSE/OBJECTIVE:To develop a mathematical model of local blood flow in the choriocapillaris using an Ising model. METHODS:A JavaScript Ising model was used to create images that emulated the development of signal voids as would be seen in optical coherence tomography angiography of the choriocapillaris. The model was produced by holding the temperature near criticality and varying the field strength. Individual frames were evaluated, and a movie video was created to show the hypothetical development of flow-related signal voids over a lifetime. RESULTS:Much the same as actual choriocapillaris images in humans, the model of flow-related signal voids followed a power-law distribution. The slope and intercept both decreased with age, as is seen in human subjects. CONCLUSION/CONCLUSIONS:This model is a working hypothesis, and as such can help predict system characteristics, evaluate conclusions drawn from studies, suggest new research questions, and provide a way of obtaining an estimate of behavior in which experimental data are not yet available. It may be possible to understand choriocapillaris blood flow in health and disease states by determining by observing deviations from an expected model.

PURPOSE/OBJECTIVE:To evaluate intravitreal aflibercept in macular telangiectasia Type 1 (MacTel 1) patients and measure their ocular angiogenic profile. METHODS:Eight subjects with MacTel 1 refractory to bevacizumab, ranibizumab, or laser therapy and switched to aflibercept were included. Best-corrected visual acuity, central macular thickness, and cystic areas quantified on optical coherence tomography B-scans were assessed during 12 months. Perifoveal capillary densities were measured on optical coherence tomography angiography. Aqueous humor was sampled from six patients and eight control subjects undergoing cataract extraction. Growth factors were quantified using a multiarray immunoassay. RESULTS:Over 12 months, patients received 6.6 ± 1.4 (range, 5-8) intravitreal aflibercept injections. Twelve months after switching to aflibercept, best-corrected visual acuity increased by ≥5 letters in 5 of 8 patients, compared with preaflibercept levels. Mean best-corrected visual acuity improved from 79.6 (∼20/50) to 88.0 (∼20/35) Early Treatment Diabetic Retinopathy Study letters (P = 0.042), and central macular thickness decreased from 434 ± 98 μm to 293 ± 59 μm (P = 0.014). Compared with control subjects, the profile of angiogenic factors in MacTel 1 eyes revealed no difference in vascular endothelial growth factor-A levels but significantly higher levels of placental growth factor (P = 0.029), soluble vascular endothelial growth factor receptor-1 (sFlt-1; P = 0.013), vascular endothelial growth factor-D (P = 0.050), and Tie-2 (P = 0.019). Placental growth factor levels inversely correlated with both superficial and deep capillary plexus densities on optical coherence tomography angiography (P = 0.03). CONCLUSION/CONCLUSIONS:The clinical response to aflibercept coupled to the angiogenic profile of MacTel 1 eyes support the implication of the placental growth factor/Flt-1 pathway in MacTel 1.

PURPOSE/OBJECTIVE:To evaluate the pattern of choriocapillaris signal voids in maternally inherited diabetes and deafness and in pseudoxanthoma elasticum in eyes before the development of any geographic atrophy. METHODS:The choriocapillaris under the central macula was imaged with the Optovue RTVue XR Avanti using a 10 μm slab thickness. Automatic local thresholding of the resultant raw data extracted areas of absent flow signal, called signal voids, and these were counted and logarithmically binned. The signal void patterns were analyzed in four eyes of two patients with maternally inherited diabetes and deafness and four eyes of three patients with pseudoxanthoma elasticum. None of the patients had geographic atrophy. These data were compared with 55 eyes of 38 healthy control subjects and analyzed with generalized estimating equations. RESULTS:The choriocapillaris images in maternally inherited diabetes and deafness and pseudoxanthoma elasticum show that the model of signal voids followed a power law distribution, but with a slope and offset much lower than the normal control group, adjusted for age (P < 0.001). The eyes in the disease group were much more likely to have signal voids greater than 40,000 μm. CONCLUSION/CONCLUSIONS:Before the development of any overt geographic atrophy, patients with maternally inherited diabetes and deafness and pseudoxanthoma elasticum show pronounced abnormalities of choriocapillaris flow. Current clinical measures of retinal pigment epithelial health only look for areas of cell death, as in geographic atrophy. It is not possible to determine from current imaging if the choriocapillaris loss precedes potential loss of function of the retinal pigment epithelium, such as secretion of vascular endothelial growth factor.