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Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC., Competing Interests: Declaration of competing interest Bailey Freund is an consultant for Bayer, Genentech, Heidelberg Engineering, Nidek, Novartis, Regeneron, and Zeiss. The author authors declare not to have conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To describe chorioretinal changes in a single case of Boucher-Neuhauser Syndrome (BNHS) over 45 years of follow-up. Methods: Retrospective chart review was performed. Color fundus photography from 1977 to 2003 was obtained and digitized. Current fundus photography was obtained with widefield imaging. High-resolution spectral-domain optical coherence tomography (OCT) was performed. Genetic analysis was performed using an inherited retinal disorders panel. Results: Fundus examination demonstrated central chorioretinal atrophy with sclerotic choroidal vessels. Short posterior ciliary arteries became more prominent and tortuous over time. Mid-peripheral atrophy extends to the equator and demonstrates a scalloped pattern with islands of atrophy intervening with areas of normal retina. The far periphery remained minimally affected. High-resolution OCT demonstrated outer retinal atrophy and choriocapillaris loss. Genetic testing showed a homozygous variant for PNPLA6 and a heterozygous variant for TYRP1. Conclusion: Chorioretinal changes in BNHS vary in onset and severity. It is important to diagnose this condition in order to begin timely management of visual and systemic sequelae., Competing Interests: Conflict of Interest Statement: None of the authors have any financial or other conflicts of interest to disclose.

Purpose: To report bilateral retinal vascular occlusive disease in limb-girdle muscular dystrophy (LGMD)., Methods: Case report., Results: A 34-year-old Asian woman was referred for evaluation and management of central retinal vein occlusion. Ultra-wide-field fluorescein angiography showed resolving initial peripheral retinal vein occlusion in one eye and peripheral venular segmental staining in the fellow asymmetric eye. Genetic testing established the diagnosis of LGMD., Conclusion: Similar to other forms of muscular dystrophy, LGMD is caused by genetic abnormalities in sarcolemma proteins, a key structural component that connects the intracellular cytoskeleton of a myofiber to the extracellular matrix. Like other muscular dystrophies, LGMD may be associated with retinal vascular abnormalities noted. In this case, retinal vascular smooth muscle dysfunction was seen in LGMD, analogous to reported vascular abnormalities in other muscular dystrophies such as facioscapulohumeral dystrophy and Duchenne muscular dystrophy., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy., Methods: Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed., Results: Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy., Conclusion: Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy ., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To establish a quantitative metric of posterior eyewall deformability in different directions of gaze in highly myopic eyes with and without posterior staphyloma., Methods: A prospective study was performed on 53 highly myopic patients (106 eyes). Ultrasound scans were acquired in primary, up, downward, nasal, and temporal gazes. A validated intensity-based segmentation algorithm was used to quantify the posterior eyewall geometry on digitalized B-scan images. Posterior eyewall local curvature (K) and distance (L) to the transducer were calculated. The associations between directions of gaze, axial length (AL), and presence of staphyloma with the K and L parameters were assessed., Results: A total of 53 participants (106 eyes) were studied. Multivariate regression analysis demonstrated that, after accounting for longer AL, and presence of staphyloma, eccentric gaze was often independently associated with various K and L parameters. Specifically, downward gaze was associated with increased posterior eyewall concavity as reflected in the maximum of K (KMax) (β = 0.050, P < 0.001) and absolute value of KMax (β = 0.041, P = 0.011). Both downward gaze and upgaze were independently associated with increase in the derivative of absolute KMax (which is consistent with more apparent, steeper staphyloma ridges), local KMax (which detects KMax at smaller intervals), and Kstd (which represents likelihood of staphyloma presence) and decrease in maximum of L (which represents movement of the staphyloma apex) with all P < 0.05. The β coefficients for downward gaze were consistently greater in magnitude compared with those in upgaze. After accounting for AL and presence of staphyloma, horizontal gazes were independently associated only with decrease in the standard deviation of L (which also represents likelihood of staphyloma presence) and maximum of L., Conclusions: Downward gaze results in a significant increase in posterior eyewall concavity in highly myopic eyes after accounting for AL and staphyloma presence. In comparison with downward gaze, upgaze resulted in a lower magnitude, but significant changes in staphyloma ridge steepness and the likelihood of staphyloma presence. Horizontal gazes seemed to be associated with less posterior eyewall geometric parameters. Studies are required to further assess the association between downward gaze during near work on posterior eyewall concavity and possible effects on myopia development and progression.

Purpose: To describe the clinical characteristics and multimodal imaging features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions.", Methods: Retrospective, observational, multicenter case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented., Results: Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8 ± 17.0 years (range, 7-78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography, chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch membrane. Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on optical coherence tomography angiography., Conclusion: Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the large number of lesions, and the high prevalence of exclusive midperipheral and far peripheral involvement may represent a distinctive phenotype of iMFC.

Background/purpose: Retinal racemose hemangioma is a rare congenital abnormality of the retinal vasculature with a variety of secondary manifestations that can cause vision loss, including macular edema. This report aims to demonstrate the use of swept-source optical coherence tomography angiography in further characterizing this abnormality., Methods: Case report with multimodal imaging including swept-source optical coherence tomography angiography., Results: A 56-year-old woman with blurred vision was diagnosed macular edema secondary to retinal racemose hemangioma. Localization of the arterial-venous connection was identified with swept-source optical coherence tomography angiography at the deep capillary plexus. Conservative management of the associated foveal exudation ultimately led to a favorable outcome., Conclusion: Observation or topical therapy may be useful and warranted in select cases of retinal racemose hemangioma. The anomalous vascular connection in retinal racemose hemangioma seems to originate at the level of the deep capillary plexus in this case; however, larger studies are necessary for corroboration. Evolving angiographic modalities such as swept-source optical coherence tomography angiography may continue to provide insights for this rare disease., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Aims: (1) To assess the morphology and 3-dimensional (3D) displacements of the eye globe and optic nerve (ON) in adduction/abduction using MRI. (2) To assess differences between healthy emmetropic and highly myopic (HM) subjects., Methods: MRI volumes of both eyes from 18 controls and 20 HM subjects in primary gaze, abduction and adduction (15°) were postprocessed. All ONs were manually segmented and fitted to a 3D curve to assess ON tortuosity. ON displacements were evaluated in four quasicoronal planes which were perpendicular to the ON in primary gaze and were 3 mm apart., Results: Axial length was higher in the HM group (28.62±2.60 vs 22.84±0.89 mm; p<0.0001). Adjusted ON tortuosities (ie, ON tortuosities estimated before myopia onset) were lower in HM eyes (0.9063±0.0591) versus controls (1.0152±0.02981) in primary gaze, adduction (0.9023±0.05538 vs 1.0137±0.0299) and abduction (0.9100±0.0594 vs 1.0182±0.0316); p<0.0001 for all cases. In all eyes, ON displacements in adduction were significantly different from those in abduction in the naso-temporal direction (p<0.0001 in all planes) but not in the supero-inferior direction. ON displacements in the posterior segments of the ON were smaller in the HM group in both gaze directions and were larger in the anterior-most ON segment in adduction only., Conclusion: The adjusted tortuosity of the ON was significantly lower in HM eyes, suggesting that eyes destined towards HM exhibited higher ON traction forces during eye movements before the onset of myopia. Our ON metrics may be valuable to explore a potential link between eye movements and axial elongation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To present the clinicopathologic correlation of indolent nonprogressive multifocal choroidal lesions, clinically presumed to be lymphoid in nature, using multimodal imaging and histopathological analysis of a donor eye., Design: Case study and clinicopathological correlation., Participants: A 77-year-old man of Caucasian ancestry with indolent, nonprogressive, multifocal, choroidal infiltration of his right eye, presumed to be lymphocytic in nature based on the appearance of the lesions, was followed up for 19 years., Methods: Multimodal imaging, including fundus photography, B-scan ultrasonography, OCT, fluorescein angiography, and indocyanine green angiography, was performed throughout the 19 years of follow-up before the patient's death. The involved eye was preserved 21 hours postmortem and analyzed using standard histopathological and immunohistochemical techniques., Main Outcome Measures: Correlation of findings on multimodal imaging with histopathological and immunohistochemical findings in the involved eye., Results: Clinical examination over the course of 19 years showed no deterioration in the visual acuity of the involved eye. Multimodal imaging revealed yellow-orange choroidal lesions that showed no appreciable progression during the 19 years of follow-up. These areas stained minimally on fluorescein angiography. Indocyanine green angiography revealed tortuous choroidal vessels and fluorescence blockage. Enhanced-depth imaging OCT revealed hyporeflective, homogenous choroidal thickening. Light microscopy, histopathology, and immunohistochemistry showed that the lesions were composed of small, mature-appearing B cells that spared the choriocapillaris. The findings were most consistent with extranodal marginal-zone lymphoma of the mucosa-associated lymphoid tissue (MALT)., Conclusions: Indolent, nonprogressive, multifocal, choroidal lymphoid lesions in this patient remained confined to the choroid, as determined based on the clinical examination and imaging for almost 2 decades, with no clinical evidence of extension into the retina. Light microscopy, histopathology, and immunohistochemistry postmortem showed that the lesions were composed of small, mature-appearing B cells that spared the choriocapillaris. The findings were consistent with extranodal marginal-zone lymphoma of the MALT. This entity is distinct from more aggressive uveal and choroidal lymphomas and is expected to remain relatively stationary on long-term clinical follow-up, with a good visual prognosis., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks, and associated systemic diseases., Methods: One hundred and twenty-six subjects with AMD were classified as SDD (with or without soft drusen) or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke., Results: There were 62 subjects with SDD and 64 non-SDD subjects, of whom 51 had CVD or stroke. SDD correlated significantly with lower mean serum high-density lipoprotein (61 ± 18 vs. 69 ± 22 mg/dL, P = 0.038, t-test), CVD and stroke (34 of 51 SDD, P = 0.001, chi square), ARMS2 risk allele (P = 0.019, chi square), but not with CFH risk allele (P = 0.66). Non-SDD (drusen only) correlated/trended with APOE2 (P = 0.032) and CETP (P = 0.072) risk alleles (chi square). Multivariate independent risks for SDD were CVD and stroke (P = 0.008) and ARMS2 homozygous risk (P = 0.038)., Conclusion: Subjects with subretinal drusenoid deposits and non-SDD subjects have distinct systemic associations and serum and genetic risks. Subretinal drusenoid deposits are associated with CVD and stroke, ARMS2 risk, and lower high-density lipoprotein; non-SDDs are associated with higher high-density lipoprotein, CFH risk, and two lipid risk genes. These and other distinct associations suggest that these lesions are markers for distinct diseases.

Type 2 idiopathic macular telangiectasia (MacTel-2) is a progressive adult-onset macular disease associated with bilateral perifoveal vascular changes, Muller cell degeneration and increased blood-retinal barrier permeability. The pathophysiological mechanisms of MacTel-2 remain unclear, however it was previously reported that anti-retinal antibodies in MacTel-2 patients are a significant feature of the disease. In this study, we aimed to compare the prevalence of anti-retinal antibodies in patients MacTel-2, healthy controls and patients with other retinal diseases. MacTel-2 patients diagnosed with multimodal imaging were enrolled and their disease severities were graded using spectral-domain optical coherence tomography. For comparison, patients with age-related macular degeneration (AMD), inherited retinal diseases (IRDs) or no retinal disease (healthy controls) were recruited as controls. Blood serum samples were screened for immunoglobulin G anti-retinal antibodies by western blotting, followed by densitometry analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and p < 0.05 considered statistically significant. Overall, anti-retinal antibody-positive cases were older (64 ± 15 vs 53 ± 17 years, p < 0.001) and females were more likely to develop anti-retinal antibodies (OR: 2.41, CI: 1.12-5.18). The frequency of anti-retinal antibody detection in MacTel-2 patients (n = 42, 36%) was not significantly different from healthy controls (n = 52, 25%) or IRD patients (n = 18, 25%) and the majority of MacTel-2 patients had no anti-retinal antibodies. In contrast, the frequency of anti-retinal antibody detection was significantly higher in patients with AMD (n = 15, 73%, p < 0.001). The lack of a greater anti-retinal antibody frequency or specificity in the MacTel-2 cohort suggests that antibody mediated immunological mechanisms may play a less significant role in MacTel-2 disease pathogenesis., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aims: Patients with BEST1 -associated autosomal dominant Best vitelliform macular dystrophy (AD-BVMD) have been reported to be hyperopic, but the prevalence of refractive error has not been described. This study aimed to characterise the type and degree of refractive error in a large cohort of patients with AD-BVMD compared with an age-similar group with ABCA4 -associated Stargardt disease., Methods: This was a retrospective chart review of consecutive patients with molecularly confirmed AD-BVMD and Stargardt macular dystrophy seen at a single academic centre. Demographic information, including age, gender and genotype were extracted from the chart. The best corrected visual acuity (BCVA), as well as type and degree of refractive error on manifest refraction for each eye on each visit, were recorded and compared., Results: A total of 178 eyes from 89 patients with AD-BVMD (35 women, 54 men; mean age 36.6 years) and 306 eyes from 153 patients (94 women, 59 men, mean age 30.2 years) with Stargardt disease were included in the study. Mean BCVA was excellent for both AD-BVMD and Stargardt eyes (logMAR 0.23 vs logMAR 0.31, respectively; p=0.55). At initial refraction, 73.0% of AD-BVMD eyes (130/178) were hyperopic, with mean spherical equivalent (SE) +1.38 dioptres (median +0.88) whereas 80.7% of Stargardt eyes (247/306) were myopic, with mean SE of -1.76 dioptres (median -1.19) (p<0.001)., Conclusion: Patients with AD-BVMD are predominantly hyperopic, whereas those with Stargardt disease are predominantly myopic. The findings provide further evidence of a role for BEST1 in ocular growth and development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To analyze the nature of multiple evanescent white dot syndrome (MEWDS) and differentiate an idiopathic or primary form of MEWDS from a secondary form that is seen in association with other clinical conditions affecting the posterior segment of the eye., Methods: Clinical and multimodal imaging findings including color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography of patients with secondary MEWDS are presented., Results: Twenty consecutive patients with secondary MEWDS were evaluated. Fifteen patients were female. Most were young adults aged between 20 to 40 years with myopia (less than -6 diopters). Pathologic conditions associated with the secondary MEWDS reaction were high myopia (greater than -6 diopters) in two eyes, previous vitreoretinal surgery for rhegmatogenous retinal detachment in 2 eyes, and manifestations of multifocal choroiditis in 18 eyes. In all eyes, the MEWDS lesions followed a course of progression and resolution independent from the underlying condition., Conclusion: Secondary MEWDS seems to be an epiphenomenon ("EpiMEWDS") that may be seen in association with clinical manifestations disruptive to the choriocapillaris-Bruch membrane-retinal pigment epithelium complex.

Purpose: To increase insight into the myopic presentation of central serous chorioretinopathy (CSC) by comparing a large group of myopic patients with CSC with reference groups with only one of the diagnoses., Methods: Myopic patients with CSC (spherical equivalent ≤-3D, n = 46), emmetropic patients with CSC (spherical equivalent -0.5 to 0.5 D, n = 83), and myopic, non-CSC patients (n = 50) were included in this multicenter cross-sectional study. Disease characteristics and imaging parameters, such as subfoveal choroidal thickness and indocyanine green angiography patterns, were compared between cases and reference groups., Results: In myopic patients with CSC, median subfoveal choroidal thickness (286 µm [IQR 226-372 µm]) was significantly thicker than subfoveal choroidal thickness in myopic, non-CSC patients (200 µm [IQR 152-228 µm], P < 0.001) but thinner than emmetropic patients with CSC (452 µm [IQR 342-538 µm], P < 0.001). They also had pachyvessels in 70% of the eyes comparable with emmetropic CSC (76%, P = 0.70). Choroidal hyperpermeability was frequently present on indocyanine green angiography in both myopic and emmetropic CSC eyes. Need for treatment, treatment success, and recurrence rate were not significantly different between CSC groups., Conclusion: Myopic CSC presents with similar imaging and clinical characteristics as emmetropic CSC, apart from their thinner choroids. Keeping in mind the structural changes of myopia, other imaging characteristics could aid the diagnostic process., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To correlate structural changes of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) with patient age., Design: Retrospective study., Participants: Fifty eyes of 49 patients (age range, 1-74 years) with CHRRPE studied at 9 tertiary vitreoretinal institutions., Methods: We analyzed the clinical findings with respect to lesion topography and pigmentation as well as investigated the OCT findings regarding the thickness, vitreoretinal interface, outer plexiform layer distortion, ellipsoid zone disruption, and retinal pigment epithelium-Bruch's membrane complex involvement of CHRRPE., Main Outcome Measures: Clinical and imaging findings of CHRRPE at different ages., Results: Analysis of 50 CHRRPE patients revealed that younger patients were more likely to demonstrate partial thickness involvement of the retina (P = 0.009) with predominantly inner retinal layer involvement (P = 0.04). The inverse was true for older patients with CHRRPE. In addition, older patients more commonly showed pigmentary changes. Eyes with CHRRPE were more likely to show an increase in central macular thickness independently of tumor location., Conclusions: Based on these findings, we believe that CHRRPE typically begins in the inner retina and continues toward the outer retina over time, with increase in central macular thickness, despite the location of the tumor., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: By optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia., Methods: In clinical OCT (61 eyes, 44 patients with AMD, 79.4 ± 7.7 years; 29 female; follow-up = 4.7 ± 0.9 years), one HRF type, RPE plume (n = 129 in 4 morphologies), was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy, 6; neovascular AMD, 3). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semiquantitatively by one observer (none, some cells, all cells)., Results: Plume morphology evolved over time and many resolved (40%). Trajectories of RPE plume and cellular debris paralleled Müller glia, including near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Müller glia remained CRALBP positive. Plume cells approached and contacted retinal capillaries., Conclusions: HRF are indicators not predictors of overall disease activity. Gain and loss of function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial-mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.

Purpose: To determine if the stress of normal eye movements results in gaze-induced globe deformations, vitreous chamber axial length and vitreous chamber axial volume (VCAV) change in highly myopic eyes., Methods: A prospective imaging study was performed on 82 eyes of 43 patients with high myopia (>27 mm of axial length) with a clinical diagnosis of staphyloma. Three-dimensional MRI scans were acquired while subjects gazed in five directions (primary, nasal, temporal, superior and inferior). Surface renderings were generated, and a processing pipeline was created to automate alignment of the eye and to measure VCAV within 5.5 mm of the visual axis for each eye in every gaze. The degree of gaze-induced globe deformation was determined by calculating the Dice coefficient to assess the degree of overlap of the sclera at each eccentric gaze with that found in primary gaze. Each eccentric gaze VCAV was compared to VCAV in primary gaze using a fixed-effects regression allowing for subject-specific and eye-specific effects., Results: The Dice coefficient showed significant gaze-induced eye shape changes in all gazes (all p<0.0001). There were no statistically significant gaze-induced VCAV changes when comparing primary gaze to nasal, temporal or upgaze. However, when changing from primary to downgaze, VCAV was increased by +4.79 mm 3 (p=0.002, 95% CI 1.71 to 7.86)., Conclusion: Significant gaze-induced globe deformation was noted in all gazes, but a reversible, instantaneous VCAV increase occurred only in downgaze, which is consistent with studies supporting the association of environmental factors such as near work with myopia development and progression., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the differential response of two distinct inflammatory signs occurring in eyes with punctate inner choroidopathy., Methods: Retrospective, observational case series using multimodal imaging., Results: Four eyes of 4 myopic female patients (mean age of 35 years, range 31-42 years) presenting with retinal manifestations of punctate inner choroidopathy. All study eyes had 2 distinct signs of active disease: 1) acute focal hyperreflective lesions splitting the retinal pigment epithelium/Bruch membrane complex on optical coherence tomography which appeared hypoautofluorescent on fundus autofluorescence and 2) more diffuse areas of outer retinal disruption limited to the ellipsoid zone and interdigitation zone on optical coherence tomography and corresponding to hyperautofluorescence on fundus autofluorescence. All patients were treated with oral prednisone and demonstrated prompt regression of the retinal pigment epithelium/Bruch membrane complex lesions with a concurrent, paradoxical centrifugal expansion of outer retinal disruption. The outer retinal disruption eventually resolved in all eyes (mean time of 6 weeks, range 4-10 weeks)., Conclusion: In patients with punctate inner choroidopathy, two distinct inflammatory signs observed with multimodal imaging display a differential response to systemic corticosteroids. Although focal inflammatory lesions splitting the retinal pigment epithelium/Bruch membrane complex seem to respond rapidly, the more diffuse, transient outer retinal disruption shows little response. This difference in treatment response may reflect different immunological phenomena with independent natural history.

Purpose: To describe the retinal findings in a 25-year-old white woman in whom a diagnosis of Boucher-Neuhäuser Syndrome (BNS) was supported by genetic testing, which identified a missense and novel nonsense mutation in the PNPLA6 gene., Methods: Observational case report of a 25-year-old woman who presented with primary amenorrhea, cerebellar ataxia, and mild retinal pigmentary abnormalities. Neurologic, endocrine, and genetic evaluations established a diagnosis of BNS., Results: Clinical examination and multimodal imaging documented focal outer retinal and retinal pigment epithelium changes including bilateral foveal stippling and a circular area of hypopigmentation in the superior macula of the left eye. Optical coherence tomography showed a linear area of outer retinal attenuation superonasal to the fovea and multiple foci of pinpoint outer retinal defects in the temporal macula of the left eye. Humphrey visual field 24-2 testing showed nonspecific defects in both eyes. Full-field electroretinography showed no evidence of a generalized retinal dysfunction., Conclusion: Recognition that the chorioretinal abnormalities occurring in BNS can be rather subtle is essential because the diagnosis of BNS may depend on their detection. To the best of our knowledge, this is the first report in the ophthalmic literature of mild chorioretinal changes in a patient with BNS testing positive for a mutation in the PNPLA6 gene.

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.

Purpose: To describe the presence of subretinal lipid globules (SLG), analyze the multimodal imaging features inherent in their optical properties, and provide a means to distinguish them from other retinal structures and clinical signs., Design: Retrospective cohort study., Methods: The clinical data and multimodal imaging features of 39 patients (49 eyes) showing SLG were evaluated. Patients underwent color fundus photography, near-infrared reflectance (NIR), spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) and OCT angiography. In vitro phantom models were used to model OCT optical properties of water, mineral oil, and intralipid droplets and to investigate the optical mechanisms producing hypertransmission tails beneath SLG., Results: The SLG were not visible in color fundus photographs or in NIR images. With both SD- and SS-OCT B-scans, SLG appeared as 31-157 μm, round, hyporeflective structures demonstrating a characteristic hypertransmission tail previously described with lipid globules found in the choroid and in neovascular membranes. Similarly, with en face OCT, SLG appeared as small, round, hyporeflective structures. SLG were encountered most often in eyes with neovascular age-related macular degeneration (AMD) that had type 1 macular neovascularization (MNV) (91.1%). Of those eyes, 93.3% were receiving intravitreal antivascular endothelial growth factor (VEGF) therapy (median of 15 injections) with a mean follow-up of 52.6 months. The number of prior injections positively correlated with the number of SLG. The detection of MNV preceded the presence of SLG in 66.7% of cases. En face OCT showed that, in many eyes (49%), SLG appeared in clusters of >10. In 38.8% of eyes, SLG were found overlying type 1 MNV, and in 44.9% of eyes, often those with more numerous SLG, the SLG were located near the lesion border. In 2 eyes with AMD followed for nonexudative type 1 MNV, SLG were detected prior to the detection of other imaging signs of exudation. SLG were observed in several other exudative macular diseases. Phantom models demonstrated that the hypertransmission tail beneath SLG is related to a lensing effect produced by these hyporeflective spherical structures., Conclusions: SLG are a newly recognized OCT feature frequently seen in eyes receiving intravitreal anti-VEGF therapy for type 1 MNV due to AMD. OCT B-scans show SLG as small, round, hyporeflective structures with a characteristic hypertransmission tail. This OCT signature is influenced by the OCT focal plane, and it relates to reduced signal attenuation through oil and a lensing effect created by a higher refractive index compared to surrounding tissue., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We describe a healthy 37-year-old man with Bartonella henselae (B. henselae) neuroretinitis with concurrent central retinal vein occlusion and ischemic optic neuropathy resulting in optic atrophy and choroidal ischemia., Methods: Case report., Results: A 37-year-old man presented with unilateral decreased vision and a fundus examination consistent with neuroretinitis. Further imaging review supported a concurrent diagnosis of central retinal vein occlusion. Although initially negative, repeat serological testing for B. henselae infection was positive. Multimodal imaging displayed severe outer retinal disruption, ischemic optic neuropathy, and choroidal ischemia. The patient demonstrated near complete resolution of fundus findings and restoration of outer retinal architecture. Residual findings included optic disk pallor and ischemic choroidopathy., Discussion: B. henselae neuroretinitis may be associated with concurrent retinal vascular occlusive disease and ischemic optic neuropathy. Central retinal vein occlusion and choroidal ischemia leading to optic nerve atrophy are additional sequelae further expanding the clinical spectrum of this entity.

Purpose: To describe the pre-exudative stage of exudative perifoveal vascular anomalous complex (ePVAC), referred to as nonexudative PVAC (nePVAC)., Design: Retrospective noncomparative case series., Methods: Patients diagnosed with nePVAC were identified at 4 retina referral centers worldwide. Multimodal retinal imaging, including structural optical coherence tomography (OCT) and OCT-angiography (OCT-A), were performed at baseline and follow-up visits., Results: Six eyes (6 patients, mean 75 ± 10 years of age) were included. Unrelated chorioretinal diseases were diagnosed in the affected eyes in 5 of 6 cases. At baseline, nePVAC is characterized by microvascular abnormalities featuring an isolated, perifoveal, large intraretinal aneurysm surrounded by capillary rarefaction at OCT-A examination, without any sign of exudation with structural OCT, and without visual impairment. Four patients were followed for a mean of 21 ± 14 months. During the follow-up, 3 of 4 eyes (75%) developed signs of exudation after a mean of 15 ± 9 months, associated with metamorphopsia and visual decline at the time of exudation. Best-corrected visual acuity decreased from 20/25 to 20/40 Snellen equivalent (P = .035) and central macular thickness increased from 268 ± 27 μm to 339 ± 65 μm (P = .145). Three patients were treated with 2.3 ± 0.6 intravitreal injections of anti-vascular endothelial growth factor without significant improvement of best-corrected visual acuity or macular edema., Conclusions: nePVAC may represent the subclinical pre-exudative stage of ePVAC, notable for an absence of exudation or visual impairment. nePVAC and ePVAC should be considered as part of the same spectrum, namely PVAC. Typically, nePVAC develops signs of exudation over time, causing metamorphopsia and visual decline and therefore these lesions warrant continued close monitoring with multimodal retinal imaging., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To describe two cases of retinal detachment with hydration folds and discuss the possible cause of these outer retinal abnormalities., Methods: The medical and imaging records of two patients with retinal detachment and hydration folds were examined., Patients: A 43-year-old myopic woman who developed a retinal detachment secondary to a macular hole and a 35-year-old man referred with a rhegmatogenous retinal detachment masquerading as an exudative detachment were each found to have retinal hydration folds., Results: On near-infrared reflectance imaging, the hydration folds appeared similar to eddy currents, and these corresponded to curvilinear outer retinal plications on optical coherence tomography. The photoreceptor outer segments appeared thickened and elongated, and there was apparent lateral expansion of the outer retinal layers., Conclusion: Hydration folds are found in rhegmatogenous retinal detachment and demonstrate reproducible imaging characteristics on near-infrared imaging and optical coherence tomography. The cause for such outer retinal plications is currently unknown. We suspect that they form as a result of hydration of the glycosaminoglycans in the interphotoreceptor matrix, which lies between the photoreceptors. Additional studies are warranted to explore this pathophysiology.

Purpose: Type 1 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) may sustain hypoxic and micronutrient-insufficient outer retinal cells compensatorily. We explored this hypothesis via histologic analysis of an eye with a shallow irregular retinal pigment epithelial elevation (SIRE) on OCT and good vision., Design: Case study and clinicopathologic correlation., Participant: A white woman with untreated nonexudative neovascular AMD and 20/30 visual acuity (left eye) and neovascular AMD (right eye), with 9 years' multimodal imaging before dying at 90 years of age., Methods: The left eye was preserved 6.25 hours after death and prepared for submicrometer epoxy resin sections and transmission electron microscopy aligned to clinical OCT B-scans. Inside and outside the MNV area, layer thicknesses, phenotypes, and vascular density of native choriocapillaris and neovessels were measured. Lengths of choriocapillaries and intervening gaps in the index eye and in early AMD eyes and healthy eyes with similar age (n = 19 each) from the Project MACULA (Maculopathy Unveiled by Laminar Analysis) online histopathologic resource (http://projectmacula.cis.uab.edu/) were measured with custom software (Caps and Gaps)., Main Outcome Measures: Descriptive features, vascular density, histologic and OCT layer thicknesses, and distribution of choriocapillaries and intervening gaps., Results: The SIRE correlated to a type 1 MNV that expanded slowly without evidence of exudation and with numerous choroidal vessels traversing Bruch's membrane defects, some visible on OCT. Tissue layers in and adjacent to the MNV area showed continuous RPE and characteristic AMD deposits. Capillary-like neovessels with fenestrations and caveolae resembling native choriocapillaris lined the retinal pigment epithelium (RPE) with a vascular density comparable with surrounding non-MNV areas. Relative to early AMD and healthy aged eyes, the index eye showed similar capillary lengths but larger gaps between vessels, indicating dropout. Outer nuclear layer thickness was preserved and showed less photoreceptor degeneration over areas of relative choriocapillaris health, including the type 1 MNV., Conclusions: Eyes with nonexudative type 1 MNV in AMD may progress to exudation, yet this stable MNV complex supported outer retinal structure for 9 years. Distinguishing features were numerous connecting vessels, high density of neovessels, continuous RPE, and slow growth. Maintaining beneficial type 1 MNV may be a therapeutic strategy., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare and unusual paraneoplastic ocular syndrome with generally poor prognosis. The authors present a case of BDUMP in a patient with bladder cancer, examined with current multimodal imaging. In the clinical setting with drusen and exudative macular detachments, the fundus simulated neovascular age-related macular degeneration, warranting standard-of-care therapy. The imaging actually showed the typical manifestations of BDUMP, but also newly recognized, associated manifestations, including the bacillary layer detachment, a gravitating retinal detachment, and multifocal choroidal hyperpermeability, but no evidence of neovascularization. Recognition of these associated manifestations is of value in appreciating the pathophysiology of this paraneoplastic disorder. Based on the imaging, the correct diagnosis was possible along with a better understanding of the nature of the clinical features in the posterior fundus. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:413-417.]., (Copyright 2020, SLACK Incorporated.)