Publications by authors named "Richard F Spaide"

306 Publications

Correction: Watersheds and mini-watersheds.

Eye (Lond) 2021 Apr 19. Epub 2021 Apr 19.

Vitreous, Macula, Retina Consultants, New York, NY, USA.

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http://dx.doi.org/10.1038/s41433-021-01502-4DOI Listing
April 2021

Watersheds and mini-watersheds.

Eye (Lond) 2021 Mar 2. Epub 2021 Mar 2.

Vitreous, Macula, Retina Consultants, New York, NY, USA.

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http://dx.doi.org/10.1038/s41433-021-01479-0DOI Listing
March 2021

Anti-Vascular Endothelial Growth Factor Dosing and Expected Acuity Outcome at 1 Year.

Authors:
Richard F Spaide

Retina 2021 Jan 11. Epub 2021 Jan 11.

Vitreous, Retina, Macula Consultants of New York, New York, NY, where the work was done.

Purpose: To determine the dose-response characteristics of the anti-vascular endothelial growth factor agents ranibizumab and aflibercept in neovascular age-related macular degeneration (NAMD) using published randomized trials and observational series.

Methods: Literature review of published series from 2006 - 2018 as determined from electronic searches of PubMed and the Cochrane Library. Data extracted included treatment strategy, frequency and first year visual acuity response. Monthly or bimonthly treatment schedules were classified as Fixed, pro re nata studies as PRN, treat and extend as TE, and when no strategy was listed, as Variable.

Results: Of 2062 citations retrieved, 96 were deemed eligible; these 96 citations provided 120 data points of dose frequency versus visual acuity change in year 1 of treatment. The dose response curve was nonlinear, but a log transform of the number of injections per year yielded a linear relationship defined by the expression, Letters of Improvement = -6.66 + 15.7*log (Number of Injections Year 1). After accounting for the number of injections neither the drug used (ranibizumab or aflibercept) nor the strategy employed (Fixed, PRN, TE, or Variable) were significant predictors of acuity change. As a group, studies using the PRN approach had the lowest number of injections and the worst acuity improvements as a treatment strategy.

Conclusions: There appears to be a predictable, mathematically defined relationship between dose frequency and visual acuity change at 1 year in NAMD. The performance of current treatment efforts, as suggested by reported series and Medicare claims data, appears to be substandard.
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http://dx.doi.org/10.1097/IAE.0000000000003116DOI Listing
January 2021

Negative Vessel Remodeling in Stargardt Disease Quantified with Volume-Rendered Optical Coherence Tomography Angiography.

Retina 2021 Jan 7. Epub 2021 Jan 7.

Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Pattern Recognition Lab, University Erlangen-Nürnberg, Erlangen, Germany Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland Department of Ophthalmology, University of Basel, Basel, Switzerland Vitreous Retina Macula Consultants, New York City, NY, US Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.

Purpose: To quantify retinal vasculature changes in Stargardt disease1 with volume-rendered optical coherence tomography angiography (OCTA).

Methods: OCTA volumes from heathy subjects and two subgroups of STGD1 patients with the presence/absence of definitely decreased autofluorescence (DDAF) areas were compared. OCTA vessel surface area (VSA) and vessel volume (VV) were measured in central zones (Z) of 1, 2 and 3mm diameter.

Results: 29 eyes of 15 STGD1 patients (20/9 eyes with/without DDAF) and 30 eyes of 15 controls contributed data. An enlarged foveal avascular zone was found in STGD1 patients without and even more with DDAF associated with a vessel rarefication in central and also paracentral zones with unnoticeable autofluorescence. VSA and VV were reduced in both STGD1 subgroups for all zones (P<0.0001). STGD1 eyes with compared to without DDAF showed reduced VSA and VV in Z2+3 (both P<0.05).

Conclusion: Volume-rendering of OCTA in STGD1 shows a reduced retinal flow in the central macula. This is most likely secondary to loss of neurosensory tissue with disease progression and therefore not likely be favorably influenced by gene transfer and retinal pigment epithelial transplantation. Retinal blood flow assessed by 3D-volume rendered OCTA could serve as surrogate marker for vascular changes of the central retina.
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http://dx.doi.org/10.1097/IAE.0000000000003110DOI Listing
January 2021

Swept Source Optical Coherence Tomography Angiography Imaging of the Choriocapillaris.

Retina 2021 Jan 4. Epub 2021 Jan 4.

From the Vitreous Retina Macula Consultants of New York, New York, USA where the work was performed.

Purpose: To analyze swept source optical coherence angiography (SS-OCTA) images acquired at different depths above and below the default location of the Zeiss PLEX Elite 9000.

Methods: Normal eyes of subjects in their 20s and 30s were evaluated. Angiographic slab images were taken at the default location of 29-49 µm below the retinal pigment epithelium (RPE) as well as 21-41 µm through 52-72 µm below in steps. The images were processed using the projection removal function from the device´s software. Raw images were evaluated, as were images that underwent a published compensation technique that adjusts for light penetration to the sampled layer.

Results: 11 eyes of 11 subjects were evaluated for the uncompensated and the compensated sets with the projection removal function turned off and on. The default location, 29-49 µm below the RPE, showed a granular choriocapillaris appearance. This appearance remained in all slabs from each group, differing slightly throughout depth. The projection removal function modified the grayscale values and diminished projection from overlaying retinal vessels. The compensation technique altered the appearance of flow deficits and the changes induced by it were more evident on the images were the projection removal function was turned on.

Conclusion: Flow images in SS-OCTA of the choriocapillaris from varying levels are similar in appearance, suggesting projection from the choriocapillaris is important in image formation, although layers of vessels in the inner choroid may contribute by various amounts. A model explaining the prominent projection artifacts observed in the choroid with SS-OCTA imaging is presented.
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http://dx.doi.org/10.1097/IAE.0000000000003109DOI Listing
January 2021

Carrots, Blueberries, and Spinach-Vision Superfoods.

Retina 2021 May;41(5):895-897

Vitreous, Retina, Macula Consultants of New York, New York, New York.

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http://dx.doi.org/10.1097/IAE.0000000000003089DOI Listing
May 2021

Imaging Features Associated with Progression to Geographic Atrophy in Age-Related Macular Degeneration: Classification of Atrophy Meeting Report 5.

Ophthalmol Retina 2020 Dec 22. Epub 2020 Dec 22.

Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Purpose: To provide an image-based description of retinal features associated with risk for development of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD), as visualized with multimodal imaging anchored by structural OCT.

Design: Consensus meeting.

Participants: International group that included those with expertise in imaging and AMD basic science and histology, and those with Reading Center experience in AMD clinical trials.

Methods: As part of the Classification of Atrophy Meeting program, an international group of experts analyzed and discussed retinal multimodal imaging features in eyes with AMD associated with GA, risk of progression to GA, or both. Attendees undertook premeeting grading exercises that were reviewed during the meeting sessions. Meeting presentations illustrated established and investigational multimodal imaging features and associated histologic features. Each of these different features were then discussed openly by the entire group to arrive at consensus definitions. These definitions were applied to 40 additional images that were graded independently by attendees to refine the consensus definitions and descriptions further.

Results: Consensus was reached on images with descriptors for 12 features. These features included components of outer retinal atrophy (e.g., ellipsoid zone disruption), components of complete retinal pigment epithelium (RPE) and outer retinal atrophy (e.g., RPE perturbation with associated hypotransmission or hypertransmission), features frequently seen in eyes with atrophy (e.g., refractile drusen), and features conferring risk for atrophy development (e.g., hyperreflective foci, drusen, and subretinal drusenoid deposits).

Conclusions: An international consensus on terms and descriptions was reached on multimodal imaging features associated GA and with risk for GA progression in eyes with AMD. We believe this information will be useful to clinicians who manage patients with AMD, researchers who study AMD disease interventions and pathogenesis, and those who design clinical trials for therapies targeting earlier AMD stages than GA expansion.
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http://dx.doi.org/10.1016/j.oret.2020.12.009DOI Listing
December 2020

Recurrent Acute Retinal Necrosis.

Retin Cases Brief Rep 2020 Dec 16;Publish Ahead of Print. Epub 2020 Dec 16.

From the Vitreous, Macula, Retina Consultants, New York, where the work was done.

Purpose: To describe a patient with recurrent acute retinal necrosis (ARN), her treatment, and propose a possible pathophysiologic mechanism.

Method: 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.
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http://dx.doi.org/10.1097/ICB.0000000000001107DOI Listing
December 2020

Reply.

Authors:
Richard F Spaide

Retina 2021 02;41(2):e26

Vitreous, Retina, Macula Consultants of New York, New York, NY.

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http://dx.doi.org/10.1097/IAE.0000000000003069DOI Listing
February 2021

The Ambiguity of Pachychoroid.

Authors:
Richard F Spaide

Retina 2021 Feb;41(2):231-237

Vitreous Macula Retina Consultants, New York, NY.

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http://dx.doi.org/10.1097/IAE.0000000000003057DOI Listing
February 2021

Reply.

Retina 2021 02;41(2):e24

Vitreous Retina Macula Consultants of New York, New York, New York.

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http://dx.doi.org/10.1097/IAE.0000000000003034DOI Listing
February 2021

INTERVORTEX VENOUS ANASTOMOSIS IN Pachychoroid-RELATED DISORDERS.

Retina 2021 May;41(5):997-1004

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; and.

Purpose: To evaluate the choroidal vascular patterns of patients with pachychoroid-related diseases in eyes images with wide-field indocyanine green angiography.

Methods: Retrospective study of wide-field indocyanine green angiographic images of patients with pachychoroid, peripapillary pachychoroid syndrome, central serous chorioretinopathy, and pachychoroid-associated neovascularization that were evaluated for anastomoses between vortex vein systems, which are ordinarily separated by a watershed zone.

Results: There were 21 subjects with a mean age of 57.4 years and 15 were male. Among the 42 eyes evaluated, central serous chorioretinopathy was found in 24 eyes (57.1%), peripapillary pachychoroid syndrome in 5 (11.9%), pachychoroid associated neovascularization in 7 (16.7%), and pachychoroid in 6 (14.3%). Every eye showed anastomosis between the superonasal, superotemporal, and inferotemporal vortex vein systems. The inferonasal vortex vein system was less likely to demonstrate anastomosis except for peripapillary pachychoroid syndrome, which showed anastomosis in all eyes. The anastomotic connections were prominent in the central macula in the central serous chorioretinopathy and pachychoroid-associated neovascularization cases, and around the nerve in the peripapillary pachychoroid syndrome cases. Although the large choroidal veins were particularly prominent in the neovascular cases, the number was fewer in the macular region than in other pachychoroid-related diseases in this series. Compared with a control group of nine eyes, the inferotemporal-superotemporal-superonasal anastomotic connections were more common in the case group (P < 0.001) and inferonasal quadrant (P = 0.023 right eye; P = 0.01, left eye).

Conclusion: Intervortex venous anastomosis is common in pachychoroid, central serous chorioretinopathy, peripapillary pachychoroid syndrome, and pachychoroid-associated neovascularization. This finding has important implications concerning pathogenesis and classification of disease.
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http://dx.doi.org/10.1097/IAE.0000000000003004DOI Listing
May 2021

CHORIOCAPILLARIS VASCULAR PARAMETERS IN NORMAL EYES AND THOSE WITH PACHYCHOROID WITH AND WITHOUT DISEASE.

Retina 2021 Apr;41(4):679-685

Vitreous, Macula, Retina Consultants, New York, NY.

Purpose: To evaluate the vascular characteristics of the choriocapillaris in eyes with pachychoroid as compared with normal controls.

Methods: Eyes with pachychoroid disease were defined as those with a history of central serous chorioretinopathy or peripapillary pachychoroid syndrome. Pachychoroid without disease was defined as eyes with no history of disease with a subfoveal choroidal thickness ≥ the age-adjusted 95th percentile thickness. Frame-averaged optical coherence tomography angiography images of the choriocapillaris obtained with a Zeiss Plex Elite were binarized, skeletonized, and evaluated for vascular branching parameters.

Results: There were 7 normal control subjects, 10 subjects with pachychoroid without disease, and 17 pachychoroid disease subjects. Mean choriocapillaris vessel segment length was 12.19 µm in eyes with pachychoroid disease as compared with 11.48 µm in normal controls and 11.62 µm in pachychoroid without disease (P = 0.003 and P = 0.006, respectively). The branches per square millimeter were fewer in pachychoroid disease (1,215), as compared with normal controls (1,471) or pachychoroid without disease (1,384; P < 0.001, and P = 0.002, respectively). The choriocapillaris vessel diameter was larger, but the fractal dimension was smaller in pachychoroid disease eyes as compared with normal eyes or pachychoroid without disease eyes. There was no statistically significant difference between normal controls and pachychoroid without disease for any measured vascular parameter of the choriocapillaris.

Conclusion: Choriocapillaris vascular parameters suggest that pachychoroid is not necessarily pathologic. It is possible that choroidal thickening is an epiphenomenon, and there are more significant vascular parameters that are related to disease. These concepts may help guide future prospective studies.
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http://dx.doi.org/10.1097/IAE.0000000000002988DOI Listing
April 2021

VARYING OPTICAL COHERENCE TOMOGRAPHY APPEARANCE OF THE INNER CHOROID WITH AGE: Possible Explanation and Histologic Correlate.

Retina 2021 May;41(5):1071-1075

Institute for Vision Research, University of Iowa, Iowa City, IA; and.

Purpose: To investigate the reflectivity of the structural optical coherence tomography images of the inner choroid as it relates to potential structural composition.

Methods: The reflectivity of slab images 29 to 49 µm and 45 to 65 µm below the retinal pigment epithelium, obtained with the Zeiss Plex Elite 9000, was evaluated. The mean and SD of a group of subjects with no ocular disorders were determined. Binarization of the images was performed and a threshold level established at the mean plus one SD for each slab depth. The proportion of area binarized was evaluated with generalized estimating equations. Representative histologic images obtained from autopsy donors were stained with Masson's trichrome, a staining method helpful in evaluating collagen and ground substance of tissue.

Results: There were 67 eyes of 38 subjects with a mean age of 44.5 (range 22-82) years. Using generalized estimating equations, age was found to be a significant predictor for the proportion of binarized pixels in both the 29 to 49 µm (P = 0.034) and the 45 to 65 µm (P < 0.001) slabs. The histologic specimens illustrated the loss of ground substance with increasing compaction of collagen fibers in the choroidal stroma with advancing age.

Conclusion: The reflectivity from the inner choroid is not uniform and changes with age. As suggested by the histologic specimens, we propose the optical coherence tomography reflectance from the inner choroid is related, in part, to the packing density of collagen fibers present there.
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http://dx.doi.org/10.1097/IAE.0000000000002985DOI Listing
May 2021

Differential reperfusion patterns in retinal vascular plexuses following increase in intraocular pressure an OCT angiography study.

Sci Rep 2020 10 5;10(1):16505. Epub 2020 Oct 5.

Vitreous, Macula, Retina Consultants, New York, USA.

To describe patterns of reperfusion in the superficial vascular plexus (SVP), deep capillary plexus (DCP) and choriocapillaris (CC) as detected on optical coherence tomography (OCTA) in cynomogulus macaque monkey model following increase in intraocular pressure by an intravitreal injection. Animal imaging study. Two cynomogulus macaque monkeys. A 100 µL intravitreal injection (IVI) of saline was given in one eye of each monkey. Serial OCTA using a Zeiss Plex Elite 9000 was used to evaluate reperfusion patterns within the SCP, DCP, and CC. OCTA evidence of perfusion. Pulsation of the central retinal artery was detected after the intraocular pressure was elevated to 98 and ≥ 99 mmHg from IVI. Episodic flow within the SVP arterioles and venules and poor visualization of flow in capillaries was noted during the initial phase of elevated pressure. As the pressure declined, the flow signal within the DCP appeared initially as dots, which progressed laterally to loops which form capillary vortex configuration. Recovery of flow within the SVP and CC appeared sooner than in the DCP. At 40 min after the injection, well after the intraocular pressure normalized, the retinal and choriocapillaris vascular perfusion showed focal defects in every layer. Compared with pre-injection images, vessel density in the DCP was 68.8% and 78.6% of baseline in monkey 1 and monkey 2, respectively. In contrast vessel density in the SVP recovered to 84.2% and 88.9% of baseline. Increases in intraocular pressure from IVI have the potential to affect every layer of blood flow in the fundus. After nominal return of intraocular pressure, focal defects in flow persisted, which may result in longer term damage to the retina.
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http://dx.doi.org/10.1038/s41598-020-73585-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536233PMC
October 2020

GENESIS OF RETINAL-CHOROIDAL ANASTOMOSIS IN MACULAR TELANGIECTASIA TYPE 2: A Longitudinal Analysis.

Retina 2021 Mar;41(3):464-470

Vitreous, Retina, Macula Consultants of New York, New York, New York.

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.
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http://dx.doi.org/10.1097/IAE.0000000000002986DOI Listing
March 2021

Non-neovascular age-related macular degeneration with subretinal fluid.

Br J Ophthalmol 2020 Sep 12. Epub 2020 Sep 12.

Ophthalmology, University of Bonn, Bonn, Germany.

Purpose: To evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes.

Methods: This retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes.

Results: Forty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy.

Conclusion: Non-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317326DOI Listing
September 2020

Autofluorescence and Yellowing Subhyaloid Blood with Proliferative Diabetic Retinopathy.

Retin Cases Brief Rep 2020 Aug 7. Epub 2020 Aug 7.

Vitreous Retina Macula Consultants of New York, New York, NY.

Purpose: 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: 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.
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http://dx.doi.org/10.1097/ICB.0000000000001041DOI Listing
August 2020

Fundus autofluorescence imaging.

Prog Retin Eye Res 2021 Mar 3;81:100893. Epub 2020 Aug 3.

Department of Ophthalmology, University of Bonn, Bonn, Germany. Electronic address:

Fundus autofluorescence (FAF) imaging is an in vivo imaging method that allows for topographic mapping of naturally or pathologically occurring intrinsic fluorophores of the ocular fundus. The dominant sources are fluorophores accumulating as lipofuscin in lysosomal storage bodies in postmitotic retinal pigment epithelium cells as well as other fluorophores that may occur with disease in the outer retina and subretinal space. Photopigments of the photoreceptor outer segments as well as macular pigment and melanin at the fovea and parafovea may act as filters of the excitation light. FAF imaging has been shown to be useful with regard to understanding of pathophysiological mechanisms, diagnostics, phenotype-genotype correlation, identification of prognostic markers for disease progression, and novel outcome parameters to assess efficacy of interventional strategies in chorio-retinal diseases. More recently, the spectrum of FAF imaging has been expanded with increasing use of green in addition to blue FAF, introduction of spectrally-resolved FAF, near-infrared FAF, quantitative FAF imaging and fluorescence life time imaging (FLIO). This article gives an overview of basic principles, FAF findings in various retinal diseases and an update on recent developments.
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http://dx.doi.org/10.1016/j.preteyeres.2020.100893DOI Listing
March 2021

CHOROIDAL BLOOD FLOW: Review and Potential Explanation for the Choroidal Venous Anatomy Including the Vortex Vein System.

Authors:
Richard F Spaide

Retina 2020 10;40(10):1851-1864

Vitreous, Retina, Macula Consultants of New York, New York, NY.

Purpose: To review control mechanisms for blood flow in the choroid, propose a system by which venous outflow is controlled by a Starling resistor, and propose an explanation for the choroidal venous architectural anatomy.

Methods: The main blood flow control mechanisms were reviewed including autoregulation, neurovascular coupling, and myogenic regulation. Applicable blood flow control mechanisms in the brain, a high flow organ in a low compliance outer shell, were used to examine analogous processes that may be occurring in the choroid.

Results: There does not seem to be effective autoregulation in the choroid, although myogenic mechanisms may be present. There is a sophisticated neural innervation that provides partial control. Like the brain, the eye has a high pulsatile blood flow rate and is encased in a noncompliant casing. As part of modulating pulsatile pressure in the cranium, the brain uses venous storage and a Starling resistor effect to modulate venous outflow. An analogous function in the eye could be provided by the choroid, which contains fascicles of large veins that converge in vortices to drain out of the eye. This vortex area seems to be where the Starling resistor effect is possible. This mechanism would have important impact on theories of many ocular diseases including central serous chorioretinopathy and spaceflight-associated neuroocular syndrome.

Conclusion: Control of blood flow is critical in the choroid, and this control seems to extend to the venous outflow system. Abnormalities in venous outflow may critically affect function in predictable pathogenic mechanisms.
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http://dx.doi.org/10.1097/IAE.0000000000002931DOI Listing
October 2020

Choroidal Venous Remodeling Documented by Long-Term Follow-up.

Retina 2020 Oct;40(10):e60-e61

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; and.

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http://dx.doi.org/10.1097/IAE.0000000000002930DOI Listing
October 2020

NOVEL METHOD FOR IMAGE AVERAGING OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGES.

Retina 2020 Nov;40(11):2099-2105

Vitreous Retina Macula Consultants of New York, New York.

Purpose: To develop a method of averaging optical coherence tomography (OCT) angiography to improve visualization of choriocapillaris structure.

Methods: A stack of OCT angiographic data from vascular layers were placed into the red-green-blue channels of a conventional digital color image. The superficial plexus was placed in the blue channel, choriocapillaris in the green, and deep vascular plexus in the red channel. The red-green-blue images derived from nine separate OCT angiographic scans were registered using an automatic registration sequence and the images were averaged. The averaged red-green-blue image was then split into the three averaged component layers. The technique is flexible and any vascular layer, such as macular neovascularization, can be used as well.

Results: The utility of the imaging method was demonstrated by showing the imaging of two different diseases. A patient with a history of familial amyloidosis, hypertension, kidney failure, kidney transplantation, and prednisone use, followed by central serous chorioretinopathy treated by photodynamic therapy. She had alterations in retinal pigment epithelial pigmentation and widespread abnormalities of autofluorescence. She showed remarkably decreased vascular density and vessel configuration of her choriocapillaris. A patient with pseudoxanthoma elasticum with subretinal drusenoid deposits at an early age also showed marked decreased choriocapillaris density and vascular configuration. These findings were compared with healthy controls of similar age with no abnormalities.

Conclusion: The detailed method is capable of averaging choriocapillaris OCT angiographic images using a simple automatic method. Image averaging offers opportunity to improve the noisy OCT angiographic images such that actual vascular structure is visible.
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http://dx.doi.org/10.1097/IAE.0000000000002877DOI Listing
November 2020

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGE COMPENSATION OF THE CHORIOCAPILLARIS INDUCES ARTIFACTS.

Retina 2020 Oct;40(10):1865-1872

Vitreous Retina Macula Consultants of New York, New York, New York.

Purpose: To analyze swept-source optical coherence angiography slab images acquired at the default level for the choriocapillaris from the Zeiss PLEX Elite 9000 before and after using a previously described imaging compensation technique.

Methods: Eyes of normal subjects, in their 20 seconds and 30 seconds, were evaluated. Angiographic slab images, 20 µm in thickness, were taken at the default location of 29 to 49 µm below the retinal pigment epithelium. These images were evaluated, as were images that underwent a published compensation technique that adjusts for light penetration to the sampled layer. Each set of images was threshold at 1 SD below the mean. Visual comparison of the swept-source optical coherence angiography images along with a quantitative analysis using a novel parameter known as multiscale structural similarity index, a measure of image similarity, was performed.

Results: Eleven eyes of 11 subjects were evaluated. The default location, 29 µm to 49 µm below the retinal pigment epithelium, showed the granular choriocapillaris appearance. Visual comparison showed that the compensation technique altered the appearance of the thresholded images, creating the appearance of new deficits while causing others to disappear. The mean multiscale structural similarity index for the original versus thresholded images and original versus thresholded compensated was 0.49 and 0.34, respectively, representing a statistically significant difference.

Conclusion: The findings of this study show that the use of a commonly used imaging compensation technique can have undesired effects on the image, and its use should be carefully considered. A model explaining the cause of such changes in the choriocapillaris swept-source optical coherence angiography images is presented.
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http://dx.doi.org/10.1097/IAE.0000000000002866DOI Listing
October 2020

Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

Ophthalmology 2020 10 25;127(10):1345-1359. Epub 2020 Apr 25.

Bascom Palmer Eye Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.

Purpose: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration.

Design: Retrospective case series.

Participants: Fifteen eyes from 12 patients identified from 10 United States centers.

Methods: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings.

Main Outcome Measures: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies.

Results: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033).

Conclusions: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.
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http://dx.doi.org/10.1016/j.ophtha.2020.04.017DOI Listing
October 2020

Optical Coherence Tomography Angiography and Fluorescein Angiography Findings in Aminoglycoside Toxicity.

Retina 2020 Jun;40(6):e26-e27

Vitreous Retina Macula Consultants of New York, New York, New York.

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http://dx.doi.org/10.1097/IAE.0000000000002822DOI Listing
June 2020

Epinephrine in the Bottle: Intraoperative vascular changes seen with intravitreal epinephrine.

Retina 2020 Jun;40(6):e24-e25

Department of Ophthalmology, New York University, New York, New York.

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http://dx.doi.org/10.1097/IAE.0000000000002817DOI Listing
June 2020

Optical coherence tomography-based consensus definition for lamellar macular hole.

Br J Ophthalmol 2020 12 27;104(12):1741-1747. Epub 2020 Feb 27.

Ophthalmology, Lariboisière Hospital, Paris, France.

Background: A consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed.

Methods: The panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions.

Results: The panel reached a consensus on the definition of three clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle's fibre layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness.

Conclusions: The use of the proposed definitions may provide uniform language for clinicians and future research.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315432DOI Listing
December 2020

ACUTE FOVEALITIS.

Retin Cases Brief Rep 2020 Feb 3. Epub 2020 Feb 3.

Vitreous Retina Macula Consultants of New York, New York.

Purpose: 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: 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: 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.
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http://dx.doi.org/10.1097/ICB.0000000000000973DOI Listing
February 2020

CUTICULAR DRUSEN: Risk of Geographic Atrophy and Macular Neovascularization.

Retina 2020 Feb;40(2):257-265

LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York.

Purpose: Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV).

Methods: A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator.

Results: A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included.

Conclusion: When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.
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http://dx.doi.org/10.1097/IAE.0000000000002399DOI Listing
February 2020