Faculty Bibliography

En face optical coherence tomography (OCT) is a practical and informative imaging modality to noninvasively visualize distinct retinal and choroidal layers by providing coronal images using boundary-specific segmentation. Ongoing research with this method is generating breakthroughs in the illustration of new perspectives of retinal disease. The clinical value of en face OCT as an advanced retinal imaging tool is growing steadily and it has unveiled many new insights into the pathoanatomy of retinal disorders. Moreover, this modality can capture various en face OCT biomarkers that correspond to different cell or tissue subtypes, which were previously only identified through histological or electron microscopy methods, underscoring the significance of this technique in providing valuable pathoanatomical information. In this comprehensive review, we will systematically summarize the en face OCT findings across a broad spectrum of retinal diseases, including disorders of the vitreoretinal interface and retinal vascular system (e.g. paracentral acute middle maculopathy or PAMM and diabetic retinopathy), in addition to the en face OCT features of other conditions such as age-related macular degeneration, pachychoroid disease spectrum, myopic degeneration, uveitis and inflammatory disorders, inherited retinal dystrophies, and drug toxicity. We will discuss and highlight the unique clinical and pathoanatomical findings uncovered with en face OCT of each these diseases mentioned above.

PURPOSE/UNASSIGNED:To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point. DESIGN/UNASSIGNED:A modified Delphi study. PARTICIPANTS/UNASSIGNED:International panel of experts in AMD, retinal imaging, and histopathology that are part of the Classification of Atrophy Meetings group. METHODS/UNASSIGNED:A modified Delphi study was undertaken to determine if there is consensus on the acceptability of the onset of end-stage atrophic AMD as a clinical end point to evaluate early interventions and the criteria for defining such an end point. Two initial rounds of online surveys were conducted. Aggregate results and anonymized comments were provided after each round, followed by a face-to-face meeting before a final survey round was completed. MAIN OUTCOME MEASURES/UNASSIGNED:Statements where consensus was reached, defined as ≥80% of responses within the 3-point bracket for agreement or disagreement based on a 9-point Likert rating scale, from a total of 33 statements included in the final round of the survey. RESULTS/UNASSIGNED:Consensus was reached for the statement that the onset of end-stage atrophic AMD was an appropriate clinical end point to evaluate early interventions (82% responses in agreement). Consensus was also reached for the statement that such an end point should be defined based on anatomical changes that have been previously shown in clinical studies to be associated with marked, but not necessarily complete, functional loss (95% responses in agreement). Consensus was nearly reached for the specific criterion that ≥90% of such atrophic AMD lesions should have ≥1 test location that was ≤10 decibels on 2 microperimetry tests (77% responses in agreement). CONCLUSIONS/UNASSIGNED:There was expert group consensus that the onset of end-stage atrophy is an appropriate clinical end point to evaluate early interventions in AMD, and that such an end point should show evidence of marked functional loss in prior clinical studies. We believe these findings will help to define incident clinical end points that are acceptable to regulatory authorities. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE/OBJECTIVE:To report a case of a full thickness macular hole (FTMH) after exposure to an extremely powerful handheld laser pointer. METHODS:We evaluated a 14-year-old male with a laser induced FTMH one month after a momentary exposure to a 5000 mW blue laser pointer. Imaging modalities including fundus color, autofluorescence, and spectral domain optical coherence tomography (SD-OCT), acquired both at our clinic and by the referring physician soon after the injury, are used to describe the clinical evolution of the case. RESULTS:Soon after the injury an intensely white, circular opacification of the retina approximately 400 µm in diameter was seen in the fovea. Early SD-OCT images showed full thickness hyperreflectivity, likely representing tissue necrosis. One month later, a FTMH and eradication of the retinal pigment epithelium at its base were evident in the fundus color, autofluorescence and SD-OCT images. CONCLUSION/CONCLUSIONS:High power laser pointers have become easily available online. The presenting findings after exposure to such high-power devices are distinct from those reported after exposure to weaker laser pointers. While long exposure to weaker lasers typically produces extensive, calligraphic figures and yellow placoid lesions involving only the outer retina, in our case a very brief exposure led to focal, full-thickness injury of the fovea.

PURPOSE/OBJECTIVE:To describe a patient with recurrent acute retinal necrosis (ARN), her treatment, and propose a possible pathophysiologic mechanism. METHOD/METHODS:Case report. RESULTS:A four-year-old girl presented elsewhere with bilateral ARN, was treated, but developed a retinal detachment in the left eye that failed vitrectomy surgery. She was referred 10 years later with recurrent ARN. The infection was difficult to get under control, but eventually responded to intravenous acyclovir and foscarnet. She was given laser photocoagulation. She was placed on oral valacyclovir prophylaxis and was disease free for 10 years at which point she decided to go to South America on vacation and stop her valacyclovir. Within a few days she developed a recurrence of ARN and flew back for treatment. She had discrete areas of retinal necrosis, vasculitis, and the laser photocoagulation lesions appeared to be ringed by a retinal change suggestive of retinitis. She responded to antiviral treatment, but developed a retinal detachment that was successfully treated. Her visual acuity was 20/20 six years later, and she was using antiviral prophylaxis. CONCLUSIONS:Recurrent ARN can respond to aggressive treatment. Chorioretinal scars, such as from photocoagulation, may be potential sites of viral invasion during recurrences. Anti-viral prophylaxis may be indicated for at risk patients.

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.

PURPOSE/OBJECTIVE:To develop a consensus nomenclature for reporting optical coherence tomography angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN/METHODS:Delphi-based survey SUBJECTS, PARTICIPANTS AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising two rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The four main areas of consensus were: definition of parameters of "widefield (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study endpoint was defined by the degree of consensus for each question: "strong consensus" was defined as ≥ 85% agreement, "consensus" as 80-84% and "near consensus" as 70-79%. MAIN OUTCOME MEASURES/METHODS:Consensus and near-consensus on OCTA nomenclature in retinal vascular disease RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥ 30% of absolute imaged area. The presence of new vessels (NV) and intra-retinal microvascular abnormalities (IRMAs), the foveal avascular zone (FAZ) parameters, the presence and amount of "no flow" area and the assessment of vessel density in various retinal layers should be added for the staging and classification of DR. Decreased flow ≥ 30% of the absolute imaged area should define an ischemic central retinal vein occlusion (CRVO). Several other items did not meet consensus requirements or were rejected in the final discussion round. CONCLUSIONS:This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

PURPOSE/OBJECTIVE:To present a patient with a subhyaloid hemorrhage from proliferative diabetic retinopathy who showed a unique contrast between the fundus autofluorescent patterns of yellow with red blood. METHODS:Analysis of color and autofluorescence fundus photographs of a patient with an aging subhyaloid hemorrhage. RESULTS:The remnants of a resorbing subhyaloid hemorrhage had two layers, a superior yellow portion that was intensely hyperautofluorescent and an inferior relatively hypoautofluorescent red portion. We argue that the yellow appearance of the devitalized blood and fluorophores imaged are related to free base porphyrins. CONCLUSION/CONCLUSIONS:Fundus autofluorescence is a useful modality to image subhyaloid blood and may lend important insights into the fluorophores that hyperfluoresce. The blood breakdown products are potentially toxic and autofluorescence imaging may offer clues to their presence.

PURPOSE/OBJECTIVE:To describe the clinical, optical coherence tomography (OCT), and OCT angiography findings of a patient with a foveal disturbance from the acute phase to the resolution of the visual disturbances. METHOD/METHODS:The patient had a comprehensive ophthalmic examination to include OCT and OCT angiography. RESULTS:A 36-year-old man presented with decreased vision and distortion in the right eye. The right eye showed yellow-white punctate opacities in the central fovea. OCT showed numerous, well-defined, globular, aggregated, hyperreflective lesions that corresponded to the visible opacities along with a focal discontinuity of the outer retinal layers. Over 3 weeks, the patient's findings resolved, and the VA improved to 20/20. No abnormalities of the choriocapillaris flow were detected using OCT angiography. The lesion resolved without pigmentary change. CONCLUSION/CONCLUSIONS:The configuration of the hyperreflective deposits, the lack of pigmentary change, and the absence of OCT angiographic findings of flow problems in the choriocapillaris argue against a primary retinal pigment epithelial or choriocapillaris abnormality as the fundamental cause of the disease. The name acute fovealitis is suggested.

PURPOSE/OBJECTIVE:To describe the long-term findings of a patient with Sorsby fundus dystrophy treated with corticosteroids and propose a mechanism by which the results were obtained. METHODS:Comprehensive ophthalmologic examination with multimodal imaging to include optical coherence tomography and optical coherence tomography angiography was used to evaluate a patient with Sorsby fundus dystrophy treated with intravitreal triamcinolone. RESULTS:A 35-year-old woman presented in 2003 with aggressive macular neovascularization in both eyes; her visual acuity was 20/25 in the right and 20/400 in the left eye. She previously had photodynamic therapy without apparent benefit. She was then treated with photodynamic therapy and an intravitreal injection of 4 mg of triamcinolone, which caused the neovascularization to become inactive. She was eventually switched to an intravitreal injection of triamcinolone 4 mg every 3 to 4 months in the right eye. She had no further treatment in the left eye because of extensive scarring. After 15 1/2 years of treatment, her visual acuity in the right eye was 20/20. Optical coherence tomography showed a large, low-level, irregular elevation of the retinal pigment epithelium. optical coherence tomography angiography revealed widespread macular neovascularization, and the choriocapillaris showed extensive loss. The patient had a TIMP-3 mutation, c.610A>T (p.Ser204Cys). CONCLUSION/CONCLUSIONS:TIMP3 has numerous effects including controlling vascular endothelial growth factor signaling and tumor necrosis factor alpha production. Corticosteroids have the potential to modulate both cytokines. This is the longest reported treatment follow-up of Sorsby fundus dystrophy with macular neovascularization, and the patient retained excellent visual acuity.

PURPOSE/OBJECTIVE:To describe a transient positive scotoma and corresponding optical coherence tomography (OCT) structural and angiographic findings. METHODS:The patient was evaluated with a comprehensive ophthalmic examination to include OCT structural and angiographic imaging with two different instruments, the Zeiss Plex Elite and the Optovue RTVue XR Avanti. RESULTS:A 45-year-old man had a sudden onset of a positive scotoma in the visual field of the left eye. No abnormalities were noted by ophthalmoscopy or fundus photography. Optical coherence tomography angiography was performed to evaluate the macular perfusion status. With each instrument, a small hyperreflective area, 175 μm in diameter, was imaged in the inner nuclear layer. The OCT angiographic images suggested a small area of decreased perfusion in the deep capillary plexus. Except for the diminutive size, the lesion had an appearance suggestive of paracentral acute middle maculopathy. The symptoms lessened rapidly, and when examined 4 days later, the lesion was less hyperreflective. Two weeks after presentation, the positive scotoma was not present and there was no longer any hyperreflectivity in the inner nuclear layer. CONCLUSION/CONCLUSIONS:Detection of the lesion was aided by using OCT angiographic scans, which have a much higher scan density than conventional OCT evaluations. The diminutive abnormality was consistent with a paracentral acute middle maculopathy lesion, although smaller than those previously reported. Micro-paracentral acute middle maculopathy lesions should be considered in the differential diagnosis of positive scotomas.