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PURPOSE: To report a case of "posterior scleral melanocytosis," a pigmented lesion of the posterior sclera that clinically resembles a flat choroidal nevus. METHODS: Case report of a patient with posterior scleral melanocytosis. Multimodal imaging, including swept source optical coherence tomography, was used to demonstrate the scleral location of the pigmented lesion and to distinguish its features from a typical choroidal nevus present in the same eye. RESULTS: An 86-year-old woman was seen for regular follow-up for neovascular age-related macular degeneration in her right eye and 2 pigmented lesions in her left eye, both presumed to be choroidal nevi. Anterior segment examination showed no evidence of ocular or dermal melanocytosis. Optical coherence tomography of the pigmented lesion in the left eye showed two distinct patterns. One lesion showed hyperreflectivity within the choroidal tissue associated with posterior shadowing, whereas the second lesion showed normal choroidal reflectivity with hyperreflectivity confined to the inner sclera associated with marked posterior shadowing. CONCLUSION: To the authors' knowledge, this is the first report of posterior scleral melanocytosis, a pigmented fundus lesion confined to the inner sclera. The need for high-penetrance optical coherence tomography to differentiate these lesions from a typical choroidal nevus may explain why this entity has not been previously described. The true nature of this entity will ultimately require histopathologic study.

PURPOSE: To report three cases of choroidal neovascularization after hormonal treatment for ovarian stimulation during a fertility therapy. METHODS: A comprehensive ophthalmic examination was performed in all cases including best-corrected visual acuity, color fundus examination, fluorescein angiography, and optical coherence tomography. RESULTS: Three females in their thirties developed unilateral acuity vision loss and metamorphopsia. They all were undergoing hormonal supplementation for ovarian stimulation with gonadotropins at the moment of presentation. Intravitreal therapy with ranibizumab was used; all cases showed a significant functional and anatomical improvement. DISCUSSION: Hormonal supplementation for fertility therapy is a common procedure that may be associated with the development of choroidal neovascularization in healthy young females. Further studies should be performed to evaluate this association, but both ophthalmologist and gynecologist should be aware of this potential complication.

PURPOSE: To analyze the changes in visual acuity and subfoveal choroidal thickness in patients with non-neovascular age-related macular degeneration (AMD) and drusenoid pigment epithelium detachments (PED). DESIGN: Consecutive observational case series. METHODS: Observational retrospective review of eyes diagnosed with drusenoid PED in a single clinical setting. Demographic and clinical data included age, sex, laterality, best-corrected visual acuity (BCVA), and subfoveal choroidal thickness measured at baseline. before and after the collapse of the PED, and at the last available follow-up. The presence of geographic atrophy (GA) was also assessed. RESULTS: Thirty-seven eyes of 25 patients (18 female) were included in the analysis. Mean age at baseline was 71 +/- 8.4 years. During a mean follow-up period of 4.9 +/-1.9 years, PED collapse was observed in 25 eyes (68%). Mean BCVA, mean maximum PED height, and mean subfoveal choroidal thickness significantly decreased from baseline to the last available follow-up (P < .001) in patients showing PED collapse. Choroidal thinning was faster during the PED collapse (speed rate of 35.9 mum/year). From those, 23 eyes (92%) developed GA. A significant correlation between the area of GA and the decrease in choroidal thickness was found (P = .010). CONCLUSIONS: Choroidal thickness significantly decreased in eyes showing drusenoid PED collapse, but not in eyes in which the PED persisted. A significant correlation with resultant GA area following PED collapse and the magnitude of choroidal thinning was found. Further studies are warranted to better understand the mechanisms involved in the occurrence of choroidal changes during the life cycle of drusenoid PEDs.

The advent of intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications has revolutionized the treatment of diabetic eye diseases. Herein, we report the outcomes of clinical studies carried out by the Pan-American Collaborative Retina Study Group (PACORES), with a specific focus on the efficacy of intravitreal bevacizumab in the management of diabetic macular edema and proliferative diabetic retinopathy. We will also discuss the use of intravitreal bevaci-zumab as a preoperative, adjuvant therapy before vitrectomy for prolif-erative diabetic retinopathy. Copyright © 2017 by Asia Pacific Academy of Ophthalmology.

Purpose: To correlate histologic results with previously recorded multimodal imaging results from a patient with type 3 neovascularization secondary to age-related macular degeneration (AMD). Design: Case study, clinical imaging, laboratory imaging, and eye-tracked clinicopathologic correlation. Participant: An 86-year-old white woman with type 3 neovascularization secondary to AMD treated with 6 intravitreal injections of bevacizumab. Methods: Multimodal retinal imaging at each clinic visit was correlated with ex vivo and high-resolution histologic images of the preserved donor eye. Clinical imaging included serial near-infrared reflectance and eye-tracked spectral-domain OCT. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding to clinical OCT signatures. Main Outcome Measures: Histologic correlates for clinical OCT signatures were sought, including reflectivity of the vascular complex, intraretinal hyperreflective foci and intraretinal cellularity, analysis of the topography of pathologic features, and evaluation of the suberetinal pigment epithelium (RPE) plus basal lamina (BL) space. Results: Clinical imaging showed a deep neovascular lesion in close relationship with a mixed serous and drusenoid pigment epithelium detachment (PED), characteristic of type 3 neovascularization. Antiangiogenic therapy achieved a complete resolution of exudation. The PED progressively flattened with each treatment, leaving a persistent triangular hyperreflectivity in the outer retina. This persistent deep lesion histologically correlated with a vascular complex implanted into sub-RPE basal laminar deposit. No connection between the choriocapillaris and the sub-RPE plus BL space was observed. Both RPE-derived and lipid-filled cells were correlated with clinical intraretinal hyperreflective foci. The sub-RPE plus BL space contained macrophages, lymphocytes, Muller cell processes, and subducted RPE. Conclusions: Clinicopathologic correlation of type 3 neovascularization showed vascular elements of retinal origin accompanied by collagenous material and Muller cell processes implanting into thick sub-RPE basal laminar deposit, which may simulate the appearance of chorioretinal anastomosis. Surrounding RPEderived and lipid-filled cells thought to be microglia correlated with clinical intraretinal hyperreflective foci. (C) 2017 by the American Academy of Ophthalmology

To analyze the multimodal imaging features in a case showing resolution of retinal pigment epithelium (RPE) apertures in association with an avascular pigment epithelium detachment secondary to nonneovascular age-related macular degeneration.

Purpose: To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. Design: Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. Participants: Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). Methods: Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. Main Outcome Measures: Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. Results: Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9 +/- 37.8 mu m and 65.4 +/- 27.9 mu m, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. Conclusions: Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging. (C) 2018 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology

Optical coherence tomography angiography is a non-invasive imaging technique that now allows for simultaneous in vivo imaging of the morphology as well as the vasculature in the eye. In this review, we provide an update on the existing clinical applications of optical coherence tomography angiography technology from the anterior to posterior segment of the eye. We also discuss the limitations of optical coherence tomography angiography technology, as well as the caveats to the interpretation of images. As current optical coherence tomography angiography systems are optimized for the retina, most studies have focused on interpreting images from conditions such as age related macular degeneration and retinal vascular diseases. However, the interpretation of these optical coherence tomography angiography images should be taken in consideration with other multi-modal imaging to overcome the limitations of each technique. In addition, there are a growing variety of clinical applications for optical coherence tomography angiography imaging in optic nerve head evaluation for glaucoma and optic neuropathies. Further developments in anterior optical coherence tomography angiography have now allowed for evaluation of anterior segment pathology such as glaucoma, ocular surface diseases, corneal vascularisation, and abnormal iris vasculature. Future developments in software could allow for improved segmentation and image resolution with automated measurements and analysis.

Purpose: To document outer retinal tubulation (ORT) formation in advanced retinal disorders. Design: Retrospective, observational study. Participants: Consecutive cases with retinal diseases showing outer retinal disruption and atrophy of the retinal pigment epithelium (RPE) associated with ORT on spectral-domain (SD) optical coherence tomography (OCT) at the final available visit. Methods: Cross-sectional SD OCT scans showing ORT at the last available visit were compared with eye-tracked baseline scans. Only patients showing the formation of ORT over time with absence of ORT at baseline were analyzed. Main Outcome Measures: Steps in ORT formation based on shapes of the external limiting membrane (ELM) descent (flat, curved, reflected, and scrolled) at the border of outer retinal and RPE atrophy, ORT characteristics (open, closed), and time between steps through a long-term follow-up. Results: From 170 eyes of 86 patients with ORT, 38 eyes of 30 patients (11 men, 19 women) with a mean age of 78.87 years (range, 56-96 years) met inclusion criteria. Of these 38 eyes, 23 (60%) had geographic atrophy secondary to age-related macular degeneration (AMD) and 2 eyes (5%) had geographic atrophy secondary to pattern dystrophy. Twelve eyes (32%) had neovascular AMD and 1 eye (3%) had neovascularization secondary to pseudoxanthoma elasticum, all showing similar ORT formative steps. Seventy-three different retinal areas (1434 cross-sectional images) were analyzed over a mean follow-up of 69.5 months (range, 21-93 months). At 73 borders, grading of eye-tracked follow-up SD OCT line scans showed a flat ELM descent at least once at 34 borders (47%), a curved ELM at 47 borders (64%), a reflected ELM at 37 borders (51%), and a scrolled ELM at 24 borders (33%). Of 81 ORTs, 73 (90%) were closed and 8 (10%) were open. The mean time for ORT formation was 14.9 months (range, 1.4-71.3 months). Conclusions: We propose progressive steps in the development of ORT and analyze the time of progression between these steps. Analyzing the borders of atrophy to determine the origin of ORT provides new insights into the pathophysiology of advanced retinal disease highlighting a role for Muller cells and may inform future therapeutic strategies. (C) 2017 by the American Academy of Ophthalmology

OBJECTIVE: To present the clinical relevance of the anatomical classification of the neovascular form of Age-Related Macular Degeneration (AMD). METHODS: Critical analysis of the current situation in the management of patients with neovascular AMD, by reviewing the available scientific evidence with regards to the classification of the types of neovascular lesion by angiography and optical coherence tomography (OCT). RESULTS: The classification of the neovascular lesion type secondary to AMD by OCT in type 1 lesions (under the pigment epithelium), type 2 (subretinal), and type 3 (retinal angiomatous proliferation), provides an added value in allowing to establish a long-term visual prognosis, an estimate of the number of treatments that a certain case may require, and a stratification of the risk for secondary geographic atrophy. CONCLUSIONS: Incorporating OCT to the initial qualitative analysis of cases with neovascular AMD offers an added value superior to that provided by the angiography, with the relevant clinical implications.

Purpose:To assess the prevalence and significance of cystic changes after internal limiting membrane peeling during epiretinal membrane surgery.Methods:A retrospective review was performed on 64 patients who underwent pars plana vitrectomy with membranectomy for idiopathic epiretinal membrane between January 2010 and January 2012 by a single physician. Pars plana vitrectomy alone (Group 1, n = 32) or in combination with phacoemulsification (Group 2, n = 32) was performed. Peeling of the epiretinal membrane was assisted by triamcinolone, and internal limiting membrane was peeled up to the vascular arcades with the aid of brilliant blue dye.Results:In Group 1, best-corrected visual acuity in logMAR (Snellen) improved from 0.53 0.29 (20/68) at baseline to 0.23 +/- 0.22 (20/34) at 6-month follow-up (P < 0.001). Two cases (6.3%) developed new cystic changes within the inner nuclear layer; however, there was no significant difference in best-corrected visual acuity at 6 months (P = 0.475). In Group 2, best-corrected visual acuity improved from 0.41 +/- 0.17 (20/51) at baseline to 0.18 +/- 0.15 (20/30) at 6 months (P < 0.001). Eight cases (25%) developed new inner nuclear layer cystic changes; however, there was no significant difference in best-corrected visual acuity at 6 months (P = 0.894).Conclusion:Development of new inner nuclear layer cystic changes after epiretinal membrane surgery may be a frequent finding, but in contrast to cystoid macular edema, it does not seem to affect visual recovery and should be observed. The combination of pars plana vitrectomy with cataract extraction may increase the risk of inner nuclear layer cystic changes.

PURPOSE: To describe the natural course, visual outcomes, and anatomic changes and provide histologic correlates in eyes with intraretinal hyperreflective foci associated with acquired vitelliform lesions. DESIGN: Retrospective cohort study and imaging histology correlation in a single donor eye. METHODS: PARTICIPANTS: Patients with intraretinal hyperreflective foci and acquired vitelliform lesions from 2 tertiary referral centers were evaluated from January 2002 to January 2014. MAIN OUTCOME MEASURES: The chronology of clinical and imaging features of retinal anatomic changes and the pattern of intraretinal hyperreflective foci migration were documented using spectral-domain optical coherence tomography (OCT). One donor eye with intraretinal hyperreflective foci was identified in a pathology archive by ex vivo OCT and was studied with high resolution light and electron microscopic examination. RESULTS: Intraretinal hyperreflective foci were associated with acquired vitelliform lesions in 25 of 254 eyes (9.8%) with a strong female preponderance (86% of patients). Focal disruptions to the ellipsoid zone and external limiting membrane overlying the acquired vitelliform lesions were observed prior to the occurrence of intraretinal hyperreflective foci in 75% of cases. Histologic evaluation showed that intraretinal hyperreflective foci represent cells of retinal pigment epithelium origin that are similar to those found in the vitelliform lesions themselves and contain lipofuscin granules, melanolipofuscin granules, and melanosomes. The occurrence of intraretinal hyperreflective foci was not a significant determinant of final visual acuity (P = .34), but development of outer retinal atrophy was (P = .003). CONCLUSIONS: Intraretinal hyperreflective foci associated with acquired vitelliform lesions are of retinal pigment epithelium origin, and the natural course and functional changes are described. (C) 2016 by Elsevier Inc. All rights reserved.