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In this Viewpoint, 2023 Lasker-DeBakey Clinical Medical Research Award winners James G. Fujimoto, David Huang, and Eric A. Swanson discuss their invention­optical coherence tomography, which allows rapid detection of diseases of the retina that impair vision.

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This guest editorial introduces the Special Section on 25 Years of OCT.

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Optical coherence tomography provides sections of tissues in a noncontact and noninvasive manner. The device measures the time delay and intensity of the light scattered or reflected from biological tissues, which results in tomographic imaging of their internal structure. This is achieved by scanning tissues at a resolution ranging from 1 to 15 µm. OCT enables real-time in situ imaging of tissues without the need for biopsy, histological procedures, or the use of X-rays, so it can be used in many fields of medicine. Its properties are not only particularly used in ophthalmology, in the diagnosis of all layers of the retina, but also increasingly in cardiology, gastroenterology, pulmonology, oncology, and dermatology. The basic properties of OCT, that is, noninvasiveness and low wattage of the used light, have also been appreciated in analytical technology by conservators, who use it to identify the quality and age of paintings, ceramics, or glass. Recently, the OCT technique of visualization is being tested in different fields of dentistry, which is depicted in the article.

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Optical coherence tomography (OCT) has made possible the structure-function correlations that uniquely characterize the afferent visual pathway as a model for understanding multiple sclerosis (MS) and for developing new treatments. During the past decade, OCT measures of retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCL + IPL) thickness have evolved from being a means to validate visual function tests, such as low-contrast letter acuity, to provide a window on the axonal and neuronal loss that are now widely recognized as contributors to permanent visual dysfunction in MS. Although acute optic neuritis (ON) leads to thinning of the RNFL by 20%-40% within 3 months after a single episode, thinning of the RNFL and GCL + IPL occur over time in MS eyes even in the absence of an acute ON history. As such, OCT and its functional and patient-reported correlates of low-contrast acuity and vision-specific quality of life (QOL) have now been incorporated into MS clinical trials. Results of an ongoing, phase 2 trial of a remyelinating agent that uses acute ON as a model for assessing therapeutic efficacy will define even further the important role for OCT in documenting structural changes as we move forward from clinical trials to clinical use.

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BACKGROUND: It is known that choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) may erode through the retinal pigment epithelium, infiltrate the neurosensory retina, and communicate with the retinal circulation in what has been referred to as a retinal­choroidal anastomosis (RCA). This is extremely common in the end stage of disciform disease. In recent years, the reverse also seems to be possible, as angiomatous proliferation originates from the retina and extends posteriorly into the subretinal space, eventually communicating in some cases with choroidal new vessels. This form of neovascular ARMD, termed retinal angiomatous proliferation (RAP) in this article, can be confused with CNV. PURPOSE: The purpose of this article is 1) to review the clinical and angiographic characteristics of a series of patients with RAP and 2) to propose a theoretical sequence of events that accounts for the neovascularized process. METHODS: In this retrospective clinical and angiographic analysis, 143 eyes with RAP (108 patients) were reviewed and classified based on their vasogenic nature and course. Clinical biomicroscopic examination, fluorescein angiography, and indocyanine green angiography were used to evaluate patients. RESULTS: The results of this series suggest that angiomatous proliferation within the retina is the first manifestation of the vasogenic process in this form of neovascular ARMD. Dilated retinal vessels and pre-, intra-, and subretinal hemorrhages and exudate evolve, surrounding the angiomatous proliferation as the process extends into the deep retina and subretinal space. One or more dilated compensatory retinal vessels perfuse and drain the neovascularization, sometimes forming a retinal­retinal anastomosis. Fluorescein angiography in these patients usually revealed indistinct staining simulating occult CNV. Indocyanine green angiography was useful to make an accurate diagnosis in most cases. It revealed a focal area of intense hyperfluorescence corresponding to the neovascularization ("hot spot") and other characteristic findings. Based on understanding of the nature and progression of the neovascularized process, patients with RAP were classified into three vasogenic stages. Stage I involved proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization [IRN]). Stage II was determined by growth of the retinal vessels into the subretinal space (subretinal neovascularization [SRN]). Stage III occurred when CNV could clearly be determined clinically or angiographically. A vascularized pigment epithelial detachment and RCA were inconsistent features of this stage. CONCLUSIONS: Retinal angiomatous proliferation appears to be a distinct subgroup of neovascular ARMD. It may present in one of three vasogenic stages: IRN, SRN, or CNV. Whereas ICG angiography is helpful in diagnosing RAP and in documenting the stage of the neovascularized process, it is frequently difficult to determine the precise nature and location of the new vessel formation. It is important for clinicians to recognize the vasogenic potential and the associated manifestations of this peculiar form of neovascular ARMD so that a proper diagnosis can be made, and when possible, an appropriate management administered.

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Optical coherence tomography (OCT) imaging has become widespread in ophthalmology over the past 15 years, because of its ability to visualize ocular structures at high resolution. This article reviews the history of OCT imaging of the eye, its current status, and the laboratory work that is driving the future of the technology.

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The historical highlights of the development of optical coherence tomography (OCT) are reviewed.

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PURPOSE: To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields. METHODS: SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 microm and 3 microm, respectively. RESULTS: Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 microm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003-.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing. CONCLUSIONS: To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials.

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