Faculty Bibliography

Importance: Macular telangiectasia type 2 (MacTel 2) is a rare disease in which abnormalities of the retinal vasculature play a key role. The vascular abnormalities are typically evaluated using fluorescein angiography, a modality with known defects in imaging the deeper layers of the retinal vasculature. Angiography based on optical coherence tomography can image vessels based on flow characteristics without dye injection and may provide improved information concerning the pathophysiology of MacTel 2. Objective: To investigate MacTel 2 using optical coherence tomographic angiography. Design, Setting, and Participants: Fourteen eyes of 7 patients with MacTel 2 were analyzed in a community-based retina practice. The flow imaging was based on split-spectrum amplitude decorrelation angiography, which can dissect layers of vessels in the retina. The inner retinal vascular plexus, the outer plexus, and deeper vascular invasion into the outer and subretinal spaces were optically dissected in en face images based on flow. Main Outcomes and Measures: Visualization and qualitative evaluation of the vascular layers of the retina as they may be affected by MacTel 2, both in terms of depth and topographic characteristics. Results: A consistent set of retinal vascular changes were seen in the eyes with MacTel 2. There was some loss of capillary density in the inner retinal vascular plexus but many more prominent alterations in the deep retinal vascular plexus. In milder forms of the disease, the deep plexus showed dilation and telangiectasis and, in more advanced cases, thinning and loss. The remaining vessels were elongated and widely spaced capillary segments. Invasion by new vessels into the outer and subretinal spaces occurred subjacent to the regions showing greatest flow imaging abnormalities in the inner and deep retinal vascular layers. Conclusions and Relevance: As evidenced by the patients in this study, important retinal vascular changes in MacTel 2 occur in the deep capillary plexus of the retina, a layer poorly visualized by fluorescein angiography and, to a lesser extent, in the inner vascular plexus. The proliferation of vessels in the outer and subretinal spaces may be in part compensatory for poor retinal perfusion by established vascular layers in the retina.

Importance: The retinal vasculature is involved in many ocular diseases that cause visual loss. Although fluorescein angiography is the criterion standard for evaluating the retina vasculature, it has risks of adverse effects and known defects in imaging all the layers of the retinal vasculature. Optical coherence tomography (OCT) angiography can image vessels based on flow characteristics and may provide improved information. Objective: To investigate the ability of OCT angiography to image the vascular layers within the retina compared with conventional fluorescein angiography. Design, Setting, and Participants: In this study, performed from March 14, 2014, through June 24, 2014, a total of 5 consecutive, overlapping B-scan OCT angiography images composed of 216 A-scans were obtained at 216 discrete positions within a region of interest, typically a 2 x 2-mm area of the retina. The flow imaging was based on split-spectrum amplitude decorrelation angiography (SSADA), which can dissect layers of vessels in the retina. These distinct layers were compared with the fluorescein angiograms in 12 healthy eyes from patients at a private practice retina clinic to evaluate the ability to visualize the radial peripapillary capillary network. The proportion of the inner vs outer retinal vascular layers was estimated by 3 masked readers and compared with conventional fluorescein angiograms of the same eyes. Main Outcomes and Measures: Outcome measures were visualization of the radial peripapillary capillary network in the fluorescein and SSADA scans and the proportion of the inner retinal vascular plexus vs the outer retinal capillary plexus as seen in SSADA scans that would match the fluorescein angiogram. Results: In none of the 12 eyes could the radial peripapillary capillary network be visualized completely around the nerve head by fluorescein angiography, whereas the network was readily visualized in the SSADA scans. The fluorescein angiograms were matched, with a mean proportion of the inner vascular plexus being 95.3% (95% CI, 92.2%-97.8%) vs 4.7% (95% CI, 2.6%-5.7%) for the outer capillary plexus from the SSADA scans. Conclusions and Relevance: Fluorescein angiography does not image the radial peripapillary or the deep capillary networks well. However, OCT angiography can image all layers of the retinal vasculature without dye injection. Therefore, OCT angiography, and the findings generated, have the potential to affect clinical evaluation of the retina in healthy patients and patients with disease.

Enhanced depth imaging of the optic nerve of a patient with a serous detachment and profound cupping of the optic nerve secondary to angle-closure glaucoma revealed a large dehiscence of the lamina cribrosa. Adjacent to the defect in the lamina were cystoid spaces within the nerve appearing to contain fluid. The most temporal of these could be seen to extend through the optic nerve and up into the macula. This visualized pathway suggests that mechanical dehiscence of the lamina may allow fluid, possibly derived from cerebrospinal fluid, to track up into the macula. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:598-600.].

PURPOSE:: To determine if pseudodrusen seen in fundus photography, particularly infrared scanning laser ophthalmoscopy, colocalize with subretinal drusenoid deposits imaged by optical coherence tomography. METHODS:: The patients were scanned with spectral domain optical coherence tomography having an A-scan spacing of 5.9 mum and a B-scan spacing of 11 mum. En face slabs were derived from this data set at distances 50 mum to 90 mum above the Bruch membrane reference plane to image the subretinal drusenoid deposit and also 6 mum below Bruch membrane to image the level of the choriocapillaris. The corresponding infrared scanning laser ophthalmoscopy image was registered to the optical coherence tomography data by aligning the retinal blood vessels in each imaging modality through elastic warping. RESULTS:: All ten eyes of nine consecutively imaged patients showed a concordance between the pseudodrusen and the subretinal drusenoid deposit in every case. At their more internal aspects, subretinal drusenoid deposits were generally isolated foci of reflectivity and with decreasing distances above the reference plane appeared to become broader, reaching confluence with neighboring deposits analogous to a topographical map of mountains. In contrast to previous reports based on optical coherence tomography, and in keeping with histologic evaluation, no patient was seen to have widespread abnormalities in choriocapillaris imaging. CONCLUSION:: This study, using an unprecedented scan density, showed that pseudodrusen appearance can be attributed to subretinal drusenoid deposits. The results of this study have widespread applicability in the understanding of age-related macular degeneration and the associations of the lesions with other structures in the outer retinal neurovascular unit.

PURPOSE: To survey the anatomic structures seen in the posterior vitreous using a newly developed technique, dynamic focusing and windowed averaging swept source optical coherence tomography. DESIGN: A cross-sectional study of subjects without a history of eye disease or posterior vitreous detachment. METHODS: A focused illumination beam was swept through the scan depth during 96 successive B-scans and the corresponding most highly resolved portion of each scan was used to make an averaged composite image. The main outcome measures were the frequency and interconnectedness of anatomic features visualized. RESULTS: There were 44 eyes of 25 subjects, who ranged in age from 23 to 62. An optically empty space was seen above the macula in all eyes, and corresponded to the premacular bursa. Above the optic nerve head was a conical space corresponding to the area of Martegiani. The two areas were interconnected in 25 (56.8%) of cases. Anterior to the premacular bursa was another lacuna, that was named the supramacular bursa, which was separate from the premacular bursa in horizontal scans centered on the fovea and found in 38 (86.4%) of eyes. Both the supra- and pre-macular bursae coursed anteriorly and in 21 (55.3%) were seen to interconnect. CONCLUSIONS: The anatomic arrangement of the vitreous is consistent in living eyes with no posterior vitreous detachment, and does not correspond precisely to that described from dissection studies of autopsy specimens. The constancy of the specific findings suggests there may be some beneficial effect from the architectural structure of the vitreous that enhances evolutionary fitness.

PURPOSE: To evaluate the concordance between pseudodrusen as manifested by subretinal drusenoid deposits and large choroidal blood vessels using stereological analysis of spectral domain optical coherence tomography (SD-OCT) images. DESIGN: Retrospective, observational, case series. METHODS: The SD-OCT images of 31 consecutive patients with the clinical appearance of pseudodrusen from a private referral retinal clinic were retrospectively reviewed. A grid of 19 evenly spaced vertical lines was randomly superimposed on each SD-OCT image using ImageJ to perform systematic uniform random sampling. The main outcome measure was the likelihood of association between subretinal drusenoid deposits and large choroidal vessels. RESULTS: Uniform random systematic sampling of 589 samples found the proportion of geometric probes intersecting subretinal drusenoid deposits to be 0.28, large choroidal vessel 0.65, and both 0.19. This value was nearly identical to the product of the joint probabilities and was within the 95% confidence interval (0.15-0.21) of the point estimate as calculated by the binomial theorem, indicating mutual independence. The subretinal drusenoid deposits were neither associated with large choroidal vessels nor the intervals in between. CONCLUSIONS: Our results demonstrate that there is no concordance between subretinal drusenoid deposits and large choroidal vessels or the stroma in between. As a consequence, hypotheses postulating that subretinal drusenoid deposits are associated with large choroidal vessels or the choroidal stromal spaces should be abandoned. Stereological techniques are powerful methods used in image evaluation in other fields of study and appear to have utility in analyzing OCT findings of the retina and choroid.

PURPOSE: To describe the microscopic structure of photoreceptors impacted by subretinal drusenoid deposits, also called pseudodrusen, an extracellular lesion associated with age-related macular degeneration (AMD), using adaptive optics scanning laser ophthalmoscopy (AOSLO). DESIGN: Observational case series. METHODS: Fifty-three patients with AMD and 10 age-similar subjects in normal retinal health were recruited. All subjects underwent color fundus photography, infrared reflectance, red-free reflectance, autofluorescence, and spectral-domain optical coherence tomography (SD-OCT). Subretinal drusenoid deposits were classified with a 3-stage OCT-based grading system. Lesions and surrounding photoreceptors were examined with AOSLO. RESULTS: Subretinal drusenoid deposits were found in 26 eyes of 13 patients with AMD and imaged by AOSLO and SD-OCT in 18 eyes (n=342 lesions). SD-OCT showed subretinal drusenoid deposits as highly reflective material accumulated internal to the retinal pigment epithelium. AOSLO revealed that photoreceptor reflectivity was qualitatively reduced by stage 1 subretinal drusenoid deposits and greatly reduced by stage 2. AOSLO presented a distinct structure in stage 3, a hyporeflective annulus consisting of deflected, degenerated or absent photoreceptors. A central core with a reflectivity superficially resembling photoreceptors is formed by the lesion material itself. A hyporeflective gap in the photoreceptor ellipsoid zone on either side of this core shown in SD-OCT corresponded to the hyporeflective annulus seen by AOSLO. CONCLUSIONS: AOSLO and multimodal imaging of subretinal drusenoid deposits indicate solid, space filling lesions in the subretinal space. Associated retinal reflectivity changes are related to lesion stages and are consistent with perturbations to photoreceptors, as suggested by histology.