Faculty Bibliography

PURPOSE: To analyze the outer retinal layers using spectral domain optical coherence tomography (SD-OCT) in patients with cone-rod dystrophy. METHODS: The diagnosis of cone-rod dystrophy was determined by primary cone involvement or concomitant loss of both cones and rods. Electroretinography showed implicit time shift at 30-Hz flicker response and prevalent decrease of photopic over scotopic responses. Using SD-OCT, the outer retina was retrospectively evaluated in 24 eyes of 12 patients with cone-rod dystrophy. From the innermost to the outermost, the four studied hyperreflective outer retinal bands were labeled Band 1, the external limiting membrane; Band 2, the ellipsoid zone; Band 3, the interdigitation zone between the cone outer segments and the apical processes of the retinal pigment epithelium; and Band 4, the retinal pigment epithelium complex. RESULTS: The mean age of study patients was 30 years, and the median visual acuity was 20/30. A ring maculopathy appearance involving the fovea area was observed in all study eyes. There was an absence of interdigitation zone in the entire length of SD-OCT scan, including the foveal area, in all 24 study eyes. Outside the foveal area, the external limiting membrane and ellipsoid zone were intact in all study eyes. The intensity of the ellipsoid zone was decreased in the entire length of SD-OCT scan in all study eyes. Within the foveal area, there was loss of the external limiting membrane and ellipsoid zone in 20 (83%) and 22 eyes (92%), respectively. The retinal pigment epithelium complex was identified in all study eyes. None of the study eyes revealed cystoid macular edema. CONCLUSION: SD-OCT scans demonstrated complete absence of the interdigitation zone in patients with cone-rod dystrophy. Consistent with the known histology of animal models of cone dystrophy, this finding may represent abnormal outer retinal morphology, including an absence of the outer segments themselves or a defective or absent interdigitation between the apical processes of the retinal pigment epithelium with the cone outer segments.

PURPOSE: To investigate the long-term clinical course of eyes with pseudodrusen appearance caused by subretinal drusenoid deposits. METHODS: Eyes from the original study identifying subretinal deposits of material as the cause of pseudodrusen appearance were evaluated in a retrospective study of outer retinal morphology. The distance between the inner plexiform layer and the retinal pigment epithelium, termed the photoreceptor length, was measured from optical coherence tomography approximately 2 mm superior to the fovea at baseline and at follow-up visits. The choroidal thickness was measured directly under this retinal area. RESULTS: Of the 21 eyes available for follow-up, 9 (42.9%) eventually developed choroidal neovascularization over a mean 2.9-year follow-up period. Regression of subretinal drusenoid deposits was seen in 9 eyes (42.9%) as well. Those with regression of subretinal drusenoid deposits had a decrease in the photoreceptor length with the final photoreceptor length being 74.4% of the initial length (P < 0.001). In eyes with regression, the underlying choroid was 81.4% of its initial value (P = 0.01) at the final follow-up. Eyes with regression also showed loss of the ellipsoid band. Eyes without regression had no change in photoreceptor length, choroidal thickness, or outer retinal architecture. CONCLUSION: Eyes with regression of subretinal drusenoid deposits develop outer retinal atrophy and loss of the underlying choroidal thickness. This finding seems common in eyes having pseudodrusen and represents a late form of age-related macular degeneration that is not in current classification systems. Further study is needed to determine both the true prevalence and the effects on visual function.

Seventy percent of the blood flow to the eye goes to the choroid, a structure that is vitally important to the function of the retina. The in vivo structure of the choroid in health and disease is incompletely visualized with traditional imaging modalities, including indocyanine green angiography, ultrasonography, and spectral domain optical coherence tomography (OCT). Use of new OCT modalities, including enhanced depth imaging OCT, image averaging, and swept-source OCT, have led to increased visualization of the choroidal anatomy. The correlation of these new anatomical findings with other imaging modalities results increases understanding of many eye diseases and recognises of new ones. The status of the choroid appears to be a crucial determinant in the pathogenesis of diseases such as age-related choroidal atrophy, myopic chorioretinal atrophy, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. Extension of these imaging techniques has provided insights into abnormalities of the sclera and optic nerve. Future developments will include blood flow information, 3D rendering of various ocular structures, and the ability to evaluate changes in 3D structural information over time (4D imaging).

PURPOSE: To evaluate optic disc drusen, extracellular protein deposits known to contain numerous aggregates of mitochondria, using multimodal modalities featuring optical coherence tomography (OCT) and autofluorescence imaging. DESIGN: Retrospective observational case series. METHODS: Eyes with optic nerve drusen were examined with enhanced depth imaging (EDI)-OCT, swept source OCT, and fundus autofluorescence using a fundus camera. RESULTS: Twenty-six eyes of 15 patients with optic disc drusen were evaluated. EDI-OCT and swept source OCT showed multiple optic disc drusen at different levels; most were located immediately anterior to the lamina cribrosa. The drusen were ovoid regions of lower reflectivity that were bordered by hyperreflective material, and in 12 eyes (46.2%) there were internal hyperreflective foci. The mean diameter of the optic disc drusen as measured in OCT images was 686.8 (standard deviation +/- 395.2) mum. There was a significant negative correlation between the diameter of the optic disc drusen and the global retinal nerve fiber layer thickness (r = -0.61, P = .001). There was a significant negative correlation between proportion of the optic disc drusen area occupied by optic nerve drusen as detected by autofluorescence imaging and the global retinal nerve fiber layer thickness (r = -0.63, P = .001). CONCLUSIONS: Deeper-penetration OCT imaging demonstrated the internal characteristics of optic disc drusen and their relationship with the lamina cribrosa in vivo. This study also showed that both the larger the drusen and the more area of the optic canal occupied by drusen, the greater the associated retinal nerve fiber layer abnormalities.

PURPOSE: To evaluate the characteristics of multifocal choroiditis and panuveitis (MCP) and punctate inner choroidopathy (PIC) using multimodal imaging. METHODS: This is a retrospective, consecutive, observational case series of 38 eyes of 22 patients. Each eye of patients with multiple yellow-white idiopathic inflammatory lesions in the fundus was classified as having MCP or PIC using standard diagnostic criteria in a masked fashion. The features of these eyes as determined from color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, and angiography were compared across diagnostic categories. The main outcome measures were the features of both MCP and PIC as evidenced by multimodal imaging. RESULTS: Of the 38 eyes, 23 eyes had MCP, 15 had PIC; and 7 patients had a discordant pairing of one diagnosis in 1 eye with the other diagnosis in the fellow eye. Acute lesions appeared as nodular collections under the retinal pigment epithelium. These solid retinal pigment epithelium detachments appeared to rupture leading to inflammatory infiltration of the subretinal space and outer retina, often with a widespread loss of the outer retinal architecture beyond the confines of the inflammatory exudate. Treatment with corticosteroids caused a rapid regression of this material with a slower resolution of the abnormalities of the outer retinal architecture. The pattern of inflammatory involvement seen by multimodal imaging did not vary between PIC and MCP. No consistent abnormalities were seen in the choroid in either condition, although there was slight thickening of the choroid underlying some acute lesions. CONCLUSION: Despite the names of these diseases, the principle sites involved appears to be the subretinal pigment epithelium and outer retinal spaces. Because both MCP and PIC target the same essential structures in the same phenotypic manner and, when active, are treated the same way, there seems to be limited clinical utility in trying to differentiate them. Based on multimodal imaging results, a reappraisal of pathogenic features and naming conventions of these diseases seems indicated.

PURPOSE: To investigate the posterior segment in cases of clinically evident intraocular inflammation for punctate reflections consistent with that expected to arise from inflammatory cells. METHODS: Patients with ocular inflammatory diseases imaged with spectral-domain optical coherence tomography (SD-OCT) were retrospectively reviewed. RESULTS: There were 7 patients with mean age of 66.7 years, and the diagnosis was toxoplasmosis in 5 eyes, multiple evanescent white dot syndrome in 1 eye, and posttraumatic outer retinitis in 1 eye. At baseline, the SD-OCT showed vitreous cells as numerous punctate spots in the vitreous in all seven eyes. The SD-OCT also showed similar-sized hyperreflective dots in the retina in all seven eyes. During follow-up, reduced vitreous cellular infiltration was correlated with a decrease in the number of the punctate spots visible by SD-OCT. CONCLUSION: Eyes with intraocular inflammation had SD-OCT images of the vitreous containing punctate spots of a size consistent with that expected from inflammatory cells. Similarly sized punctate spots were seen within the retina in regions of retinitis. Additional characterization of the optical section should permit stereological estimations of actual cell counts per unit volume.

PURPOSE: To examine histomorphometrically the macular region of highly myopic eyes. METHODS: On horizontal anterior-posterior histological sections, we examined the posterior pole of 138 human globes (axial length: 20-35 mm). In the parapapillary region, we differentiated between the beta zone (Bruch's membrane without RPE), gamma zone (parapapillary region without Bruch's membrane), and delta zone (elongated and thinned gamma zone). RESULTS: In 12 (8.7%) eyes, a macular Bruch's membrane defect (MBMD) was detected. The MBMD showed a complete lack of RPE and choriocapillaris, and an almost complete lack of photoreceptors. Presence of MBMD was associated with longer axial length (P < 0.001), longer gamma zone (P = 0.04) and delta zone (P < 0.001), thinner peripapillary scleral flange, and thinner sclera just outside of the optic nerve meninges (P < 0.001) and at the posterior pole (P < 0.001). An MBMD was found only in eyes with an axial length of 27 mm or longer. MBMD prevalence in highly myopic eyes was 12/39 or 30.8%. MBMD presence was not significantly related to length of beta zone (P = 0.09). In multivariate binary regression analysis, MBMD presence was significantly (P < 0.001) associated only with axial length. CONCLUSIONS: Highly myopic eyes (axial length >/=27mm) can show an MBMD associated with complete loss of RPE and choriocapillaris, and marked reduction of photoreceptors and large choroidal vessels. MBMD presence was strongly associated with axial length and indirectly with parapapillary gamma zone and delta zone. The myopia-associated secondary MBMDs may occur parallel to the myopia-associated widening of Bruch's membrane opening around the optic nerve head.

PURPOSE: To characterize the morphology, prevalence, and topography of subretinal drusenoid deposits, a candidate histological correlate of reticular pseudodrusen, with reference to basal linear deposit (BlinD), a specific lesion of age-related macular degeneration, and to propose a biogenesis model for both lesion. METHODS: Donor eyes with median death-to-preservation of 2:40 hours were postfixed in osmium tannic acid paraphenylenediamine and prepared for macula-wide high-resolution digital sections. Annotated thicknesses of 21 chorioretinal layers were determined at standard locations in sections through the fovea and the superior perifovea. RESULTS: In 22 eyes of 20 white donors (83.1 +/- 7.7 years), SDD appeared as isolated or confluent drusenoid dollops punctuated by tufts of retinal pigment epithelium apical processes and associated with photoreceptor perturbation. Subretinal drusenoid deposits and BlinD were detected in 85 and 90% of non-neovascular age-related macular degeneration donors, respectively. Subretinal drusenoid deposit was thick (median, 9.4 mum) and more abundant in the perifovea than in the fovea (P < 0.0001). BlinD was thin (median, 2.1 mum) and more abundant in the fovea than in the perifovea (P < 0.0001). CONCLUSION: Subretinal drusenoid deposits and BlinD prevalence in age-related macular degeneration eyes are high. Subretinal drusenoid deposits organized morphology, topography, and impact on surrounding photoreceptors imply specific processes of biogenesis. Contrasting topographies of subretinal drusenoid deposits and BlinD suggest relationships with differentiable aspects of rod and cone physiology, respectively. A 2-lesion 2-compartment biogenesis model incorporating outer retinal lipid homeostasis is presented.