PATHWAYS TO GEOGRAPHIC ATROPHY IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To characterize and quantify the precursor lesions of geographic atrophy in eyes with age-related macular degeneration. METHODS: A retrospective study of eyes with a minimum of 6-month follow-up before developing geographic atrophy. Evaluations included color and autofluorescence imaging, along with spectral-domain optical coherence tomography, employing definitions from the Consensus of Atrophy Meeting Group and Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group. RESULTS: There were 55 eyes of 44 patients, who had a mean age of 81.3 years at onset of atrophy; 35 (63.6%) were female. The mean duration of follow-up before and after the advent of geographic atrophy was 4.9 years and 1.2 years, respectively. Geographic atrophy was preceded by collapse of a druse in 41 eyes (74.5%). Of these, 29 (70.7%) were drusenoid pigment epithelial detachments. Among the eyes with regressing drusen, there were 9 with overlying vitelliform deposit, and all had concurrent subretinal drusenoid deposit; however, 19 of 30 eyes with no vitelliform deposit overlying the druse had concurrent subretinal drusenoid deposit, a difference that was significant ( P < 0.001). Regression of subretinal drusenoid deposit was found in 4 eyes (7.3%), regression of vitelliform deposit associated with subretinal drusenoid deposit in 5 (9.1%), and regression of vitelliform deposit in eyes concurrently harboring drusen was found in 3 (5.4%) and regression of vitelliform deposit alone in 2 (3.6%) at the site of eventual development of geographic atrophy. CONCLUSION: Geographic atrophy appears to develop from multiple pathways as manifested by the many precursor lesions, all various forms of extracellular deposit, that upon regression, result in a common end-stage appearance.

PROGRESSION OF PERIPAPILLARY AND MACULAR CHORIORETINAL ATROPHY IN MULTIFOCAL CHOROIDITIS IS ASSOCIATED WITH PERIATROPHIC INFLAMMATORY PLUMES.

PURPOSE: To investigate peripapillary atrophy and macular chorioretinal scars in eyes affected by multifocal choroiditis and panuveitis. METHODS: This retrospective cohort study reviewed the medical records, fundus photographs, and spectral-domain optical coherence tomographic scans of 31 eyes from 19 patients. RESULTS: Patients had a mean age of 45 years (range 24-69 years). The average follow-up duration was 7 years (range, 2.5-14.5 years), with 14 patients undergoing immunosuppressive treatment. In the group of 31 eyes, 20 showed peripapillary plumes of ill-defined hyperreflectivity at the termination border of the retinal pigment epithelium. These plumes, extending from bare Bruch membrane to the outer nuclear layer, sometimes undermined the adjacent retinal pigment epithelium. They responded to corticosteroid treatment and resembled the material under the retinal pigment epithelium in acute lesions. Among 20 eyes with these peripapillary inflammatory lesions, 16 (80%) experienced increased atrophy, in contrast to none in the eyes without these lesions ( P < 0.001). Similar patterns were observed at the edges of macular chorioretinal atrophy. This observation occurred in patients using immunosuppressive medication who were otherwise thought to be under adequate control. CONCLUSION: In patients with multifocal choroiditis and panuveitis, previously unrecognized plumes of smoldering inflammatory activity at the borders of chorioretinal atrophy appears to be linked to atrophy expansion. The recognition of this phenomenon may require a reappraisal of treatment of multifocal choroidopathies to help mitigate the expansion of atrophy in these eyes.

HEALING MECHANISMS AFTER MACULAR HOLE REPAIR SUGGESTS PROCESS OF FOVEATION.

PURPOSE: To evaluate the long-term healing of the fovea following macular hole surgery in light of the processes known to occur during the maturation of the fovea during childhood, in which there is migration of the inner retinal layers away from and the photoreceptors toward the center of the macula. METHODS: Consecutive patients with longer than 1 year of follow-up were evaluated with spectral-domain optical coherence tomography. The interinner nuclear layer distance, which was the separation across the fovea of the midpoints of the inner nuclear layers, and the ONL (outer nuclear layer) to RPE (retinal pigment epithelium) thicknesses were measured. RESULTS: There were 22 eyes of 21 patients, 16 of whom were female; the mean age was 65.6 years. Initially, after the surgery, there was closure of the hole with continuity of the inner and middle layers of the retina across the previous macular hole. Over time, there was a migration of the inner retinal layers away from and movement of the ONL toward the center of the macula. The mean interinner nuclear layer distance increased from 352 µ m to 549 µ m ( P = 0.001), and the ONL-RPE thickness increased from 77 µ m to 146 µ m ( P < 0.001). The mean logMAR acuity improved 6.5 lines. CONCLUSION: Healing of a macular hole after surgery seems to recapitulate the development of the macula in childhood. The process of foveation may have evolutionary benefit of optimizing macular function after injury despite the absence of effective replication of the highly specialized, postmitotic photoreceptors.

COMPLEMENT INHIBITION FOR GEOGRAPHIC ATROPHY: Review of Salient Functional Outcomes and Perspective.

PURPOSE: To evaluate available rationale and outcomes of randomized trial results for complement inhibition for geographic atrophy. METHODS: Data from recently completed randomized trials of complement inhibition, particularly for pegcetacoplan and avacincaptad pegol, were evaluated for both the outcome, area of autofluorescence loss, and functional vision tests. RESULTS: Pegcetacoplan 2 mg showed statistically significant reduction in expansion of the area of autofluorescence loss with monthly, but not every-other-month dosing, in a 12-month phase two trial. Nearly 40% of patients recruited for the monthly arm did not complete the treatment. In two parallel phase 3 studies there was a statistically significant reduction in the area of atrophy in one but not both studies as compared with untreated controls. Data released at 24 months follow-up showed statistically significant reduction in the area of autofluorescence-detected atrophy in both studies compared with sham. Patients did not show functional difference in best-corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and mean microperimetry threshold sensitivities in the treatment versus sham arms. Avacincaptad pegol was evaluated in two randomized pivotal studies and showed a statistically significant reduction in the expansion of autofluorescence loss at 12 months. Patients in the treatment arms did not show any difference as compared with sham in the best-corrected visual acuity or low luminance visual acuity, the only functional outcomes mentioned. Both drugs increased the risk of macular neovascularization. CONCLUSION: Both avacincaptad pegol and pegcetacoplan show significant differences compared with sham in autofluorescence imaging but no benefit in visual function at 12 and 24 months, respectively.

THE WAY PATIENTS SEE FLOATERS: Widefield Dynamic Scanning Laser Ophthalmoscopy Imaging of Vitreous Abnormalities.

PURPOSE: To investigate the use of dynamic widefield scanning laser ophthalmoscopy (SLO) and B-scan ultrasonography in imaging vitreous abnormalities in patients with complaints of floaters. METHODS: Twenty-one patients underwent both dynamic SLO and B-scan ultrasonography to image their vitreous abnormalities. After reviewing these videos, patients graded each imaging technique on a scale of 1 to 10, based on how closely it represented their visual perception of floaters. RESULTS: The mean age of the patients (12 women and nine men) was 47.7 ± 18.5 years. The patients graded a median score of nine for SLO imaging (mean = 8.43) compared with a median score of 5 (mean = 4.95) for ultrasound ( P = 0.001). Widefield SLO imaging demonstrated three-dimensional interconnectivity within the condensations of the formed vitreous that exhibited translational and rotational movements with eye saccades. CONCLUSION: Floaters are a common complaint, but it is difficult to know whether imaging findings of the vitreous correlate to what patients perceive. Widefield SLO seems to image vitreous abnormalities related to how patients perceive their own floaters better than B-scan ultrasonography. Despite the term "floaters", the vitreous abnormalities in the videos seemed to be manifestations of a complex three-dimensional degeneration of the vitreous framework.

Inside out: Relations between the microbiome, nutrition, and eye health.

Age-related macular degeneration (AMD) is a complex disease with increasing numbers of individuals being afflicted and treatment modalities limited. There are strong interactions between diet, age, the metabolome, and gut microbiota, and all of these have roles in the pathogenesis of AMD. Communication axes exist between the gut microbiota and the eye, therefore, knowing how the microbiota influences the host metabolism during aging could guide a better understanding of AMD pathogenesis. While considerable experimental evidence exists for a diet-gut-eye axis from murine models of human ocular diseases, human diet-microbiome-metabolome studies are needed to elucidate changes in the gut microbiome at the taxonomic and functional levels that are functionally related to ocular pathology. Such studies will reveal new ways to diminish risk for progression of- or incidence of- AMD. Current data suggest that consuming diets rich in dark fish, fruits, vegetables, and low in glycemic index are most retina-healthful during aging.

UNSUSPECTED CENTRAL VISION DECREASE FROM MACULAR GANGLION CELL LOSS AFTER POSTERIOR SEGMENT SURGERY.

PURPOSE: To describe a novel postsurgical complication of circumscribed macula ganglion cell loss as an apparent cause of unsuspected vision loss following posterior segment surgery. METHODS: Patients were seen in referral and were evaluated with comprehensive examination to include optical coherence tomography and microperimetry. RESULTS: All eight patients had a sudden central vision loss following vitrectomy, and many patients suspected the central loss was present even before the eye patch was removed on the first postoperative day. Of the eight patients, one had a vitrectomy with no membrane peeling, whereas the remaining seven had membrane peeling. The mean postoperative visual acuity was 20/200. The mean ganglion cell layer volume was 0.69 µm3 in the involved eye and 1.035 µm3 in the fellow eye (P < 0.001). The global retinal nerve fiber layer thicknesses in the involved and fellow eyes were 81.3 and 90 µm, respectively (P = 0.08). The outer retinal architecture was unremarkable in the involved eyes and did not appear to explain the poor acuity. The ganglion cell layer volume loss was not necessarily associated with retinal nerve fiber layer thicknesses that were in the abnormal range or in optic nerve pallor. Microperimetry showed severe depression of the threshold sensitivities. CONCLUSION: Severe loss of the macular ganglion cells may occur after vitrectomy and is associated with central vision loss. The diagnosis is made by having a high index of suspicion when examining optical coherence tomography B-scan images and by evaluating ganglion cell layer volumes. The frequency of this occurrence is currently unknown.

IMAGING THE VITREOUS WITH A NOVEL BOOSTED OPTICAL COHERENCE TOMOGRAPHY TECHNIQUE: Posterior Vitreous Detachment.

PURPOSE: To evaluate the anatomic changes in the vitreous associated with evolving posterior vitreous detachment over the macula. METHODS: A novel scanning method by which four A-scans at each position were averaged before the Fourier transform that boosted the image quality sufficiently such that frame averaging could occur. B-scans and volume rendered images of eyes with evidence of any partial separation of the vitreous in the macular regions were evaluated. RESULTS: There were 43 eyes of 23 subjects with particular attention paid to the findings of seven eyes with various stages of posterior vitreous detachment occurring over the macula. In eyes from young subjects with no vitreous degeneration, the outer vitreous showed a diffuse, poorly defined increase in reflectivity in the region where the vitreous cortex was expected to be. In eyes with vitreous degeneration, there was a hyperreflective zone, called the cortical vitreous condensation, that coursed parallel to the curvature of the retina. The posterior vitreous face elevated from the retina with either a well-defined, smooth outer surface, consistent with the posterior vitreous membrane, or a poorly defined flocculent outer border. The cortical vitreous near the fovea was thin and in eyes in the process of posterior vitreous detachment had visible tears. In more advanced eyes, a circular dehiscence of the cortical vitreous in the central macula occurred with herniation of the vitreous gel through the hole. CONCLUSION: The methodology produced images of unprecedented clarity that highlighted several newly described details concerning the vitreous changes associated with posterior vitreous detachment over the macula.

REGIONAL SCLERAL THICKNESS AS A RISK FACTOR FOR CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To evaluate regional sclera thicknesses as possible risk factors for central serous chorioretinopathy (CSC). METHODS: Patients with CSC and controls were evaluated with contact B-scan ultrasonography using a 20 Mhz concentric phased array ultrasound unit and enhanced depth imaging optical coherence tomography to measure the scleral thickness at the equator and posterior pole. The resultant data were evaluated using univariate analysis and generalized estimating equations. RESULTS: There were 40 patients with CSC with a mean age of 58 years and 23 controls with a mean age of 60.7 years (P = 0.31). The mean subfoveal scleral thicknesses were 1.3 mm in the CSC group and 0.86 mm in the control group (P < 0.001). The mean equatorial scleral thickness was 0.61 mm in the CSC group and 0.42 mm in the control group (P < 0.001). Using generalized estimating equations, the equatorial scleral thickness (P = 0.001), posterior scleral thickness (P < 0.001), and subfoveal choroidal thickness (P = 0.032) were independent predictors of CSC. Once these variables were entered into the equation, neither sex nor age were significant predictors. Generalized estimating equation analysis showed that equatorial, but not posterior, scleral thickness was a significant predictor of subfoveal choroidal thickness. CONCLUSION: Scleral thicknesses of the posterior and equatorial portions of the eye were found to be significant predictors of CSC, consistent with what was proposed in the theory of venous overload choroidopathy. Direct measurement by high resolution ultrasonography provides independent information about specific regions of the sclera and also avoids making speculative assumptions derived from anterior segment measurements.

SAUSAGING AND BULBOSITIES OF THE CHOROIDAL VEINS IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To evaluate the caliber of the choroidal veins in central serous chorioretinopathy, a disease proposed to be associated with overloading of choroidal venous outflow. METHODS: Widefield indocyanine green angiograms of eyes with central serous chorioretinopathy were graded for sausaging defined as three or more contiguous fusiform dilations that vary by at least 50% from the narrowest to largest diameters. A bulbosity was defined as a focal 2X dilation of a blood vessel as compared with the diameter of the surrounding host vessel. The data underwent statistical analysis including the use of generalized estimating equations. RESULTS: There were 73 eyes of 41 patients with a mean age of 53.5 years. Sausaging of vessels was seen in a mean and median of three quadrants per eye. Using generalized estimating equations, the only significant risk factor for sausaging was the use of corticosteroids. The two significant predictors of subfoveal choroidal thickness using generalized estimating equations were age ( P = 0.021) and proportion of quadrants involved by sausaging ( P < 0.001). The decrease in choroidal thickness per year of age was estimated to be 3.7 µ m, while the increase with four quadrant involvement with sausaging was estimated to be 236 µ m. There were a total of 39 bulbosities in 26 eyes (35.6%), preferentially involving intervortex venous anastomoses. CONCLUSION: Variations in the venous caliber are very common in eyes with central serous chorioretinopathy and seems to be associated with pathophysiologic alterations related to increased pressure within and remodeling of the larger choroidal veins. This may lead to overloading of the choriocapillaris with leakage as one manifestation.

DENOISING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY VOLUMETRIC SCANS USING A DEEP LEARNING MODEL.

PURPOSE: To evaluate the use of a deep learning noise reduction model on swept source optical coherence tomography volumetric scans. METHODS: Three groups of images including single-line highly averaged foveal scans (averaged images), foveal B-scans from volumetric scans using no averaging (unaveraged images), and deep learning denoised versions of the latter (denoised images) were obtained. We evaluated the potential increase in the signal-to-noise ratio by evaluating the contrast-to-noise ratio of the resultant images and measured the multiscale structural similarity index to determine whether the unaveraged and denoised images held true in structure to the averaged images. We evaluated the practical effects of denoising on a popular metric of choroidal vascularity known as the choroidal vascularity index. RESULTS: Ten eyes of 10 subjects with a mean age of 31 years (range 24-64 years) were evaluated. The deep choroidal contrast-to-noise ratio mean values of the averaged and denoised image groups were similar (7.06 vs. 6.81, P = 0.75), and both groups had better maximum contrast-to-noise ratio mean values (27.65 and 46.34) than the unaveraged group (14.75; P = 0.001 and P < 0.001, respectively). The mean multiscale structural similarity index of the average-denoised images was significantly higher than the one from the averaged--unaveraged images (0.85 vs. 0.61, P < 0.001). Choroidal vascularity index values from averaged and denoised images were similar (71.81 vs. 71.16, P = 0.554). CONCLUSION: Using three different metrics, we demonstrated that the deep learning denoising model can produce high-quality images that emulate, and may exceed, the quality of highly averaged scans.

IMAGING THE VITREOUS WITH A NOVEL BOOSTED OPTICAL COHERENCE TOMOGRAPHY TECHNIQUE: Vitreous Degeneration and Cisterns.

PURPOSE: To evaluate the degenerative findings including cistern formation in the premacular vitreous using optical coherence tomography. METHODS: A novel enhanced vitreous imaging method by which four A-scans at each position were averaged before the Fourier transform increased the image quality per frame so that subsequent image registration for averaging could occur. Analysis of B-scans and volume-rendered images of eyes in subjects of various ages was performed. RESULTS: There were 43 eyes of 23 subjects ranging in age from 23 to 68 years. The texture in the vitreous images suggests specific orientations of the vitreous fibers in the macular region; there were fibers circumferential to the retina immediately anterior to the premacular bursa. The pattern of the vitreous fibers seemed less well-defined internal to the zone of circumferential fibers. In younger eyes, there were striations oriented in a roughly inferior to superior direction in this zone. In older eyes, there were striations in the same orientation but actually were alternating zones of vitreous synchysis and syneresis. In these same eyes, numerous cisterns appeared at various levels in the vitreous gel. With extensive vitreous condensation and synchysis, definition of the premacular bursa was lost. CONCLUSION: With this novel method of enhanced vitreous imaging, the vitreous seemed to have stereotypic patterns of degeneration. The formation of vitreous syneresis and synchysis may be related to organization architecture of the vitreous, including the pattern of vitreous collagen deposition, and the effects of eye motion through decades of time.

ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR DOSING AND EXPECTED ACUITY OUTCOME AT 1 YEAR.

PURPOSE: To determine the dose-response characteristics of the antivascular endothelial growth factor agents ranibizumab and aflibercept in neovascular age-related macular degeneration using published randomized trials and observational series. METHODS: Literature review of published series from 2006 to 2018 as determined from electronic searches of PubMed and the Cochrane Library. Data extracted included treatment strategy, frequency, and first year visual acuity response. Monthly or bimonthly treatment schedules were classified as Fixed, pro re nata studies as PRN, treat and extend as TE, and when no strategy was listed, as Variable. RESULTS: Of 2062 citations retrieved, 96 were deemed eligible; these 96 citations provided 120 data points of dose frequency versus visual acuity change in Year 1 of treatment. The dose-response curve was nonlinear, but a log transform of the number of injections per year yielded a linear relationship defined by the expression, Letters of Improvement = -6.66 + 15.7*log (number of injections Year 1). After accounting for the number of injections neither the drug used (ranibizumab or aflibercept) nor the strategy used (Fixed, pro re nata, treat and extend, or Variable) were significant predictors of acuity change. As a group, studies using the pro re nata approach had the lowest number of injections and the worst acuity improvements as a treatment strategy. CONCLUSION: There seems to be a predictable, mathematically defined relationship between dose frequency and visual acuity change at 1 year in neovascular age-related macular degeneration. The performance of current treatment efforts, as suggested by reported series and Medicare claims data, seems to be substandard.

INTERMEDIATE AND DEEP CAPILLARY PLEXUSES IN MACHINE LEARNING SEGMENTATION OF HIGH-RESOLUTION OPTICAL COHERENCE TOMOGRAPHY IMAGING.

PURPOSE: To describe imaging produced by machine learning-based segmentation of high-resolution optical coherence tomography imaging of the intermediate capillary plexus and deep capillary plexus, layers of vessels not imaged well by dye-based angiography. METHODS: Three healthy subjects with no ocular problems were imaged with spectral domain optical coherence tomography using an instrument with a scanning speed of 85,000 A-scans per second and 3 µm axial optical resolution. A random forest segmentation strategy was used to segment the intermediate capillary plexus and deep capillary plexus. The depth-resolved imaging data was visualized with the help of volume rendering. RESULTS: The high-resolution optical coherence tomography showed the intermediate capillary plexus and deep capillary plexus at the outer borders of the inner nuclear layer. These vessels could be visualized with unprecedented detail in three dimensions. There were multiple bridging vessels connecting to the whorl-like patterns of capillary mesh of the deep capillary plexus, a feature only previously imaged in histologic evaluation of excised eyes. CONCLUSION: High-resolution optical coherence tomography, machine learning, and advanced image display techniques have wide relevancy in studying the retina in health and disease. Application of this approach has provided images of the deeper vascular layers of the eye that approximate histologic imaging, but noninvasively.

CHORIOCAPILLARIS VASCULAR PARAMETERS IN NORMAL EYES AND THOSE WITH PACHYCHOROID WITH AND WITHOUT DISEASE.

PURPOSE: To evaluate the vascular characteristics of the choriocapillaris in eyes with pachychoroid as compared with normal controls. METHODS: Eyes with pachychoroid disease were defined as those with a history of central serous chorioretinopathy or peripapillary pachychoroid syndrome. Pachychoroid without disease was defined as eyes with no history of disease with a subfoveal choroidal thickness ≥ the age-adjusted 95th percentile thickness. Frame-averaged optical coherence tomography angiography images of the choriocapillaris obtained with a Zeiss Plex Elite were binarized, skeletonized, and evaluated for vascular branching parameters. RESULTS: There were 7 normal control subjects, 10 subjects with pachychoroid without disease, and 17 pachychoroid disease subjects. Mean choriocapillaris vessel segment length was 12.19 µm in eyes with pachychoroid disease as compared with 11.48 µm in normal controls and 11.62 µm in pachychoroid without disease (P = 0.003 and P = 0.006, respectively). The branches per square millimeter were fewer in pachychoroid disease (1,215), as compared with normal controls (1,471) or pachychoroid without disease (1,384; P < 0.001, and P = 0.002, respectively). The choriocapillaris vessel diameter was larger, but the fractal dimension was smaller in pachychoroid disease eyes as compared with normal eyes or pachychoroid without disease eyes. There was no statistically significant difference between normal controls and pachychoroid without disease for any measured vascular parameter of the choriocapillaris. CONCLUSION: Choriocapillaris vascular parameters suggest that pachychoroid is not necessarily pathologic. It is possible that choroidal thickening is an epiphenomenon, and there are more significant vascular parameters that are related to disease. These concepts may help guide future prospective studies.

PULSATILE FILLING OF DILATED CHOROIDAL VESSELS IN MACULAR WATERSHED ZONES.

PURPOSE: To describe pulsatile filling of dilated choroidal veins in the watershed zones and propose an alteration in choroidal perfusion pressure. METHODS: Retrospective review of original and digital subtraction indocyanine green angiography. RESULTS: We observed pulsating blood flow within choroidal vein segments in the posterior pole in 14 eyes (diagnosis of polypoidal choroidal vasculopathy, central serous chorioretinopathy, or neovascular age-related macular degeneration). Pulsating dye front was observed in single or multiple large choroidal vein(s) in a location that is ordinarily a watershed zone between the segmental areas of venous drainage, and vessels proximal and distal were often dilated. The pulsatile venous segments filled more slowly than the neighboring veins. In digital subtraction indocyanine green angiography, the dye front advanced in an incremental fashion or oscillated in a back-and-forth manner during several cardiac cycles during the filling of these larger choroidal veins. With indocyanine green angiography, we observed dilated choroidal veins that violated the macula watershed zone, localized bulbous dilations, and arteriole-over-vein crossings with apparent compression. CONCLUSION: These novel observations suggest the pressure gradient for flow in the affected veins varied from low gradients when the filling was slow to high gradients when the filling was faster. The vessels violated the physiological watershed zone and seem to function as anastomoses between the ordinarily segmented venous drainage of the choroid. The dilated segments may result in pooling of venous blood as part of venous outflow abnormalities that may be operative in these diseases.

VARYING OPTICAL COHERENCE TOMOGRAPHY APPEARANCE OF THE INNER CHOROID WITH AGE: Possible Explanation and Histologic Correlate.

PURPOSE: To investigate the reflectivity of the structural optical coherence tomography images of the inner choroid as it relates to potential structural composition. METHODS: The reflectivity of slab images 29 to 49 µm and 45 to 65 µm below the retinal pigment epithelium, obtained with the Zeiss Plex Elite 9000, was evaluated. The mean and SD of a group of subjects with no ocular disorders were determined. Binarization of the images was performed and a threshold level established at the mean plus one SD for each slab depth. The proportion of area binarized was evaluated with generalized estimating equations. Representative histologic images obtained from autopsy donors were stained with Masson's trichrome, a staining method helpful in evaluating collagen and ground substance of tissue. RESULTS: There were 67 eyes of 38 subjects with a mean age of 44.5 (range 22-82) years. Using generalized estimating equations, age was found to be a significant predictor for the proportion of binarized pixels in both the 29 to 49 µm (P = 0.034) and the 45 to 65 µm (P < 0.001) slabs. The histologic specimens illustrated the loss of ground substance with increasing compaction of collagen fibers in the choroidal stroma with advancing age. CONCLUSION: The reflectivity from the inner choroid is not uniform and changes with age. As suggested by the histologic specimens, we propose the optical coherence tomography reflectance from the inner choroid is related, in part, to the packing density of collagen fibers present there.

INTERVORTEX VENOUS ANASTOMOSIS IN Pachychoroid-RELATED DISORDERS.

PURPOSE: To evaluate the choroidal vascular patterns of patients with pachychoroid-related diseases in eyes images with wide-field indocyanine green angiography. METHODS: Retrospective study of wide-field indocyanine green angiographic images of patients with pachychoroid, peripapillary pachychoroid syndrome, central serous chorioretinopathy, and pachychoroid-associated neovascularization that were evaluated for anastomoses between vortex vein systems, which are ordinarily separated by a watershed zone. RESULTS: There were 21 subjects with a mean age of 57.4 years and 15 were male. Among the 42 eyes evaluated, central serous chorioretinopathy was found in 24 eyes (57.1%), peripapillary pachychoroid syndrome in 5 (11.9%), pachychoroid associated neovascularization in 7 (16.7%), and pachychoroid in 6 (14.3%). Every eye showed anastomosis between the superonasal, superotemporal, and inferotemporal vortex vein systems. The inferonasal vortex vein system was less likely to demonstrate anastomosis except for peripapillary pachychoroid syndrome, which showed anastomosis in all eyes. The anastomotic connections were prominent in the central macula in the central serous chorioretinopathy and pachychoroid-associated neovascularization cases, and around the nerve in the peripapillary pachychoroid syndrome cases. Although the large choroidal veins were particularly prominent in the neovascular cases, the number was fewer in the macular region than in other pachychoroid-related diseases in this series. Compared with a control group of nine eyes, the inferotemporal-superotemporal-superonasal anastomotic connections were more common in the case group (P < 0.001) and inferonasal quadrant (P = 0.023 right eye; P = 0.01, left eye). CONCLUSION: Intervortex venous anastomosis is common in pachychoroid, central serous chorioretinopathy, peripapillary pachychoroid syndrome, and pachychoroid-associated neovascularization. This finding has important implications concerning pathogenesis and classification of disease.

GENESIS OF RETINAL-CHOROIDAL ANASTOMOSIS IN MACULAR TELANGIECTASIA TYPE 2: A Longitudinal Analysis.

PURPOSE: To longitudinally characterize structural/angiographic findings of retinal-choroidal anastomosis (RCA) in macular telangiectasia Type 2 (MacTel2). METHODS: A combined retrospective/prospective review of patients with MacTel2 with >2 visits and >2 months follow-up, including examination, fundus photography, fluorescein angiography, spectral-domain optical coherence tomography, and projection-resolved optical coherence tomography angiography. RESULTS: There were 24 eyes of 12 patients with a mean age of 61.1 (±7.3 [SD]) years and median follow-up of 447 (range 81-1,511) days. There were five eyes diagnosed with new RCA after not having any previously. Retinal-choroidal anastomosis was diagnosed in 8 (33%) eyes initially and eventually 13 (54%). In the eight eyes initially diagnosed with RCA, the number of RCAs and outer retinal hyperrflective lesions increased over the follow-up. The RCAs were found in clusters, generally temporal to the fovea. Retinal-choroidal anastomosis was uniformly associated with complete retinal subsidence, defined as the loss of outer nuclear layer substance such that the middle retinal layers sank down toward the retinal pigment epithelium (RPE), and was also present in each case. Each RCA colocalized with a region of hyperreflectivity, previously termed an outer retinal hyperreflective lesion. There was a lack of fluorescein leakage, lipid, hemorrhage, or any structural correlates with fluid exudation, and no signs of subretinal/subretinal pigment epithelium neovascularization. CONCLUSION: De novo RCA development seems to be associated with retinal subsidence, and after RCAs form, they increase in number and topographic distribution over time. Initially after formation, there was no sign of exudation. These data suggest the descent of the deep capillary plexus occurs with RCA, devoid of subretinal/subretinal pigment epithelium neovascularization in MacTel2.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGING OF THE CHORIOCAPILLARIS.

PURPOSE: To analyze swept-source optical coherence angiography images acquired at different depths above and below the default location of the Zeiss PLEX Elite 9000. METHODS: Normal eyes of subjects in their 20s and 30s were evaluated. Angiographic slab images were taken at the default location of 29 µm to 49 µm below the retinal pigment epithelium and 21 µm to 41 µm through 52 µm to 72 µm below in steps. The images were processed using the projection removal function from the device's software. Raw images were evaluated, as were images that underwent a published compensation technique that adjusts for light penetration to the sampled layer. RESULTS: Eleven eyes of 11 subjects were evaluated for the uncompensated and the compensated sets with the projection removal function turned off and on. The default location, 29 µm to 49 µm below the retinal pigment epithelium, showed a granular choriocapillaris appearance. This appearance remained in all slabs from each group, differing slightly throughout depth. The projection removal function modified the grayscale values and diminished projection from overlaying retinal vessels. The compensation technique altered the appearance of flow deficits, and the changes induced by it were more evident on the images were the projection removal function was turned on. CONCLUSION: Flow images in swept-source optical coherence angiography of the choriocapillaris from varying levels are similar in appearance, suggesting projection from the choriocapillaris is important in image formation, although layers of vessels in the inner choroid may contribute by various amounts. A model explaining the prominent projection artifacts observed in the choroid with swept-source optical coherence angiography imaging is presented.