Quantifying cardiac dysfunction and valvular heart disease associated with subretinal drusenoid deposits in age-related macular degeneration.

BACKGROUND/AIMS: Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent valvular heart disease (VHD) and reduced systemic perfusion via cardiac index (CI). METHODS: Post-hoc analysis of cross-sectional study. 200 intermediate AMD (iAMD) subjects were assigned by masked readers to two groups: SDD (with or without drusen) and drusen (only) based on multimodal ophthalmic imaging. 65 transthoracic echocardiograms (TTEs) reports were available for cardiologist evaluation of VHD severity of the four cardiac valves and the presences of precursor lesions of aortic sclerosis (ASc) and mitral annular calcification (MAC). Necessary parameters to calculate CI were also obtained. Univariate testing was performed using Fisher's Exact test and t-test. RESULTS: 82.6% (19/23) of the iAMD subjects with at least one moderate/severe VHD had concurrent SDDs (p = 0.0040). All cases of aortic regurgitation (6/6, p = 0.0370) and mitral regurgitation (13/13, p = 0.0004) were found with coexisting SDDs. Stenotic VHD was not significantly associated with SDDs, however 70.7% of subjects with ASc (29/41, p = 0.0108) and 76.0% of subjects with MAC (19/25, 0.0377) had coexisting SDDs. CI was available in 48 subjects and was significantly below normal levels in the SDD cohort (mean CI SDD 1.95 ± 0.60 L/min/m2, non-SDD 2.71 ± 0.73 L/min/m2, p = 0.0004). CONCLUSIONS: Several specific VHDs have been found associated with the SDD form of AMD. Decreased systemic perfusion as measured by CI was also associated with SDDs, which supports a perfusion hypothesis of SDD pathogenesis. Further research is warranted to understand the relationship between cardiovascular disease and SDDs.

Macular atrophy and focal choroidal excavation in a patient with JAG1- related alagille syndrome.

INTRODUCTION: Alagille syndrome (AGS) is a genetic disease with multisystemic affection, including ocular manifestations. Recently, a high frequency of posterior segment findings, including macular changes, has been reported. This publication aims to report an unusual finding of macular atrophy and a focal choroidal excavation in a patient with JAG1 related AGS. METHODS: Case report. RESULTS: This publication describes an atypical presentation of focal choroidal excavation (FCE) and unilateral macular atrophy in a 7-year-old male with Alagille syndrome (AGS). Genetic analysis revealed a pathogenic variant in the JAG1 gene. Ophthalmological examination and imaging findings demonstrated characteristic ocular manifestations of AGS, including posterior embryotoxon, chorioretinal atrophy, and thinning of the choroid. CONCLUSION: The presence of FCE in AGS is uncommon, and the underlying mechanisms remain unclear. Further exploration of similar cases is necessary to better understand the evolution and visual prognosis in patients with AGS and FCE.

This case report highlights the presence of focal choroidal excavation and unilateral macular atrophy in a patient with Alagille syndrome. The genetic analysis identified a pathogenic variant in the JAG1 gene.

Correlation between ellipsoid zone thickness and the presence of subretinal drusenoid deposits in age-related macular degeneration.

PURPOSE: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage. METHODS: Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51-100; 61% women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000 µm nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction. RESULTS: The mean EZ thickness differences between the SDD+D and drusen-only groups were (in µm) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p≤0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p≤0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age. CONCLUSION: Subjects with SDDs (±drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.

Subretinal drusenoid deposits, age-related macular degeneration, and cardiovascular disease.

Decades of studies on age-related macular degeneration (AMD), cardiovascular disease and stroke have not found consistent associations between AMD and systemic vascular disease. This study suggests that there is in fact no general relationship, but instead a strong, specific association between only the subretinal drusenoid deposit (SDD) phenotype of AMD on retinal imaging and certain co-existent vascular diseases that are high risk for compromised cardiac output or internal carotid artery stenosis. Future screening initiatives for these high -risk vascular diseases (HRVDs) with fast, inexpensive retinal imaging could make a significant contribution to public health and save lives. Likewise, screening patients with known HRVDs for unrecognized AMD of the SDD form could enable needed treatment and save vision.

Retinal Pigment Epithelial Detachments Devoid of Retinal Pigment Epithelium.

PURPOSE: To describe two patients with chronic central serous chorioretinopathy (CSC) showing what appeared to be retinal pigment epithelium detachments (PED) lacking imaging findings consistent with retinal pigment epithelium (RPE) over the elevation. METHOD: The patients underwent comprehensive ophthalmic examination, including multicolor fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). RESULTS: A 70-year-old male and a 58-year-old male, both diagnosed with chronic CSC, showed PED-like lesions that were hypoautofluorescent, suggesting an absence of RPE. SD-OCT B-scans showed serous, dome-shaped elevations composed of a narrow, mildly hyperreflective band (9-10 µm thick) that demonstrated hypertransmission of light. The material that constituted the elevation was contiguous with the outer portion of the RPE band at the lesion borders. CONCLUSION: Based on the multimodal imaging findings we hypothesize that these elevations of the retina have lost their overlying RPE. A thin layer of material that could represent a residual layer of basal laminar deposit produced by the RPE remains overlying the detachments, possibly accounting for their dome shape and structural stability.

Unilateral COVID-19-associated vasculitic central retinal vein occlusion: phlebitis with subhyaloid, intraretinal and subretinal hemorrhages.

PURPOSE: To describe unilateral vasculitic central retinal vein occlusion (CRVO) in a young adult whose vision problems preceding system symptoms of COVID-19 infection. METHODS: Observational clinical case report. RESULTS: A 39-year-old immunocompetent male without prior ocular disease presented for vitreoretinal care complaining of decreasing vision in his right eye for two weeks. Headaches, pharyngitis and coughing began four days after his visual symptoms. COVID-19 testing was negative prior to initial vitreoretinal evaluation and positive afterward. Dilated and tortuous major retinal veins in his right eye had prominent perivascular sheathing. A large subhyaloid hemorrhage spanned the macula. Subretinal hemorrhages were present in areas of sheathing and diffuse nerve fiber layer hemorrhages were arrayed in the distribution of the radial peripapillary capillary plexus. Laboratory tests for inflammatory diseases were negative. The patient was hospitalized for COVID-19 pneumonia a few days after his initial vitreoretinal evaluation. Pars plana vitrectomy was performed for persistent subhyaloid hemorrhage eight weeks after his hospitalization. The visual acuity in the patient's right eye improved from CF to 20/30 post-operatively. CONCLUSION: The patient's findings are consistent with an atypical CRVO which we hypothesize to be of vasculitic origin because of prominent associated retinal phlebitis and venous sheathing. Concomitant subhyaloid, nerve fiber layer and subretinal hemorrhages involved the superficial and deep retinal vascular complexes. The patient's COVID-19-related hospitalization and systemic management delayed surgical management of his subhyaloid hemorrhages but a good visual result was achieved despite persistence of macular preretinal blood for three months.

Half-Fluence, Half-Dose Photodynamic Therapy: Less Direct Damage but More Inflammation?

Objective: To present clinical findings and multimodal imaging of three patients who developed bacillary layer detachments (BALADs) shortly after half-fluence, half-dose (HFHD) verteporfin photodynamic therapy (PDT). Methods: Retrospective observational case series. Three patients were treated with HFHD-PDT for (1) macular neovascularisation five years after resolved central serous chorioretinopathy (CSC), (2) persistent serous retinal detachment (SRD) from chronic CSC, and (3) neovascular age-related macular degeneration with persistent SRD despite intravitreal anti-VEGF therapy. Results: Each patient developed a BALAD after HFHD-PDT. Acute fulminant exudation caused subretinal fluid expansion into the inner photoreceptor layer, cleaving myoid from ellipsoid zones in the central macula. Subretinal fluid and the BALADs subsequently resolved over 6-8 weeks. Conclusions: The subretinal fluid and BALAD following HFHD-PDT were transient and did not cause photoreceptor damage over a 6-month follow-up period. We speculate that the reduced-impact HFHD protocol decreases direct tissue damage but increases proinflammatory cytokines. The long-term pathophysiological consequences of the resolved BALADs are unknown.

THE WAY PATIENTS SEE FLOATERS: Widefield Dynamic Scanning Laser Ophthalmoscopy Imaging of Vitreous Abnormalities.

PURPOSE: To investigate the use of dynamic widefield scanning laser ophthalmoscopy (SLO) and B-scan ultrasonography in imaging vitreous abnormalities in patients with complaints of floaters. METHODS: Twenty-one patients underwent both dynamic SLO and B-scan ultrasonography to image their vitreous abnormalities. After reviewing these videos, patients graded each imaging technique on a scale of 1 to 10, based on how closely it represented their visual perception of floaters. RESULTS: The mean age of the patients (12 women and nine men) was 47.7 ± 18.5 years. The patients graded a median score of nine for SLO imaging (mean = 8.43) compared with a median score of 5 (mean = 4.95) for ultrasound ( P = 0.001). Widefield SLO imaging demonstrated three-dimensional interconnectivity within the condensations of the formed vitreous that exhibited translational and rotational movements with eye saccades. CONCLUSION: Floaters are a common complaint, but it is difficult to know whether imaging findings of the vitreous correlate to what patients perceive. Widefield SLO seems to image vitreous abnormalities related to how patients perceive their own floaters better than B-scan ultrasonography. Despite the term "floaters", the vitreous abnormalities in the videos seemed to be manifestations of a complex three-dimensional degeneration of the vitreous framework.

BACILLARY LAYER DETACHMENT AFTER PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To report the clinical and optical coherence tomography findings of a patient with chronic central serous chorioretinopathy who developed a short-term bacillary layer detachment after photodynamic therapy (PDT). METHODS: A 56-year-old man presented with metamorphopsia and 20/100 visual acuity in his right eye. He was diagnosed with active, chronic central serous chorioretinopathy based on clinical findings and multimodal imaging. His visual problems and retinal findings persisted for 3 months before he was treated with half-fluence, half-dose verteporfin PDT. RESULTS: The patient had a prominent decrease in his vision postoperatively. Two days after treatment, multimodal imaging showed a marked increase in exudation that merged preoperative neurosensory retinal detachments. A prominent subfoveal bacillary layer detachment was also present. The subretinal fluid and bacillary layer detachment resolved over the next 8 weeks, with a return of visual acuity to its baseline level and normalization of retinal structures except for a small zone of subfoveal ellipsoid zone and interdigitation zone disruption. CONCLUSION: Half-fluence, half-dose verteporfin PDT caused a fulminant increase in subretinal fluid and an associated subfoveal bacillary layer detachment. We hypothesize that chronic central serous chorioretinopathy-related chorioretinal dysfunction contributed to the severe PDT-induced local inflammatory reaction that caused the patient's bacillary layer detachment. Hyperacute choroidal exudation too fulminant for containment in subretinal space extended into and exceeded photoreceptor inner segment tensile strength, cleaving the myoid layer and/or dissecting it from the ellipsoid layer. This finding broadens the causality spectrum of bacillary layer detachments and vision losses that can follow PDT.

Longitudinal follow-up and outcome analysis in central serous chorioretinopathy.

OBJECTIVES: To analyse the longitudinal changes in visual acuity and risk factors for recurrence or development of choroidal neovascularisation (CNV) in eyes with acute or chronic central serous chorioretinopathy (CSCR). METHODS: This was a retrospective, multicentric, longitudinal, observational study done in patients with a diagnosis of unilateral or bilateral CSCR and having at least 4 years of follow-up between the years 1999 and 2020. Kaplan-Meier curves were used for assessing cumulative risks. Multivariate logistic, linear and cox regression models were used for risk factor analyses. The trend in visual acuity, cumulative risks of recurrence and CNV formation was analysed. RESULTS: A total of 117 out of 175 eyes (66.8%) had stable or improvement in vision at last follow-up, while 24 eyes had more than/equal to 3 line loss of vision. Four eyes (7.7%) with acute CSCR at initial presentation developed features of chronic CSCR at the final presentation. Thirty-seven eyes had recurrence during the follow-up with a 10-year cumulative recurrence rate of around 30%. On Cox proportional hazard regression analysis, history of previous treatment and male gender (p = 0.03) were associated with a lower risk of recurrence. Twenty-four developed de novo CNV by the end of follow-up and higher age (p = 0.001) and a higher number of recurrences (p = 0.05) were associated with a higher risk of early de novo CNV formation. The cumulative 10-year CNV development rate was 17.4%. CONCLUSION: A non-temporal relationship between acute and chronic CSCR was seen. Previous treatment, smoking and baseline RPE abnormality affected recurrence of SRF or CNV formation.

RETINAL RACEMOSE HEMANGIOMA (RETINAL ARTERIOVENOUS COMMUNICATION) DIAGNOSED AND MANAGED WITH MULTIMODAL IMAGING.

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.

Combined Therapeutic Penetrating Keratoplasty and Pars Plana Vitrectomy for the Treatment of Infectious Keratitis Endophthalmitis: Mexican Endophthalmitis Study Group Protocol 4.

PURPOSE: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. METHODS: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. RESULTS: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). CONCLUSIONS: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.

Scanning laser ophthalmoscopy retroillumination: applications and illusions.

Scanning laser ophthalmoscopes (SLOs) are used widely for reflectance, fluorescence or autofluorescence photography and less commonly for retroillumination imaging. SLOs scan a visible light or near-infrared radiation laser beam across the retina, collecting light from each retinal spot as it's illuminated. An SLO's clinical applications, image contrast and axial resolution are largely determined by an aperture overlying its photodetector. High contrast, reflectance images are produced using small diameter, centered apertures (confocal apertures) that collect retroreflections and reject side-scattered veiling light returned from the fundus. Retroillumination images are acquired with annular on-axis or laterally-displaced off-axis apertures that capture scattered light and reject the retroreflected light used for reflectance imaging. SLO axial resolution is roughly 300 µm, comparable to macular thickness, so SLOs cannot provide the depth-resolved chorioretinal information obtainable with optical coherence tomography's (OCT's) 3 µm axial resolution. Retroillumination highlights and shades the boundaries of chorioretinal tissues and abnormalities, facilitating detection of small drusen, subretinal drusenoid deposits and subthreshold laser lesions. It also facilitates screening for large-area chorioretinal irregularities not readily identified with other en face retinal imaging modalities. Shaded boundaries create the perception of lesion elevation or depression, a characteristic of retroillumination but not reflectance SLO images. These illusions are not reliable representations of three-dimensional chorioretinal anatomy and they differ from objective OCT en face topography. SLO retroillumination has been a useful but not indispensable retinal imaging modality for over 30 years. Continuing investigation is needed to determine its most appropriate clinical roles in multimodal retinal imaging.

The Blue Light Hazard Versus Blue Light Hype.

PURPOSE: The blue light hazard is the experimental finding that blue light is highly toxic to the retina (photic retinopathy), in brief abnormally intense exposures, including sungazing or vitreoretinal endoillumination. This term has been misused commercially to suggest, falsely, that ambient environmental light exposure causes phototoxicity to the retina, leading to age-related macular degeneration (AMD). We analyze clinical, epidemiologic, and biophysical data regarding blue-filtering optical chromophores. DESIGN: Perspective. METHODS: Analysis and integration of data regarding the blue light hazard and blue-blocking filters in ophthalmology and related disciplines. RESULTS: Large epidemiologic studies show that blue-blocking intraocular lenses (IOLs) do not decrease AMD risk or progression. Blue-filtering lenses cannot reduce disability glare because image and glare illumination are decreased in the same proportion. Blue light essential for optimal rod and retinal ganglion photoreception is decreased by progressive age-related crystalline lens yellowing, pupillary miosis, and rod and retinal ganglion photoreceptor degeneration. Healthful daily environmental blue light exposure decreases in older adults, especially women. Blue light is important in dim environments where inadequate illumination increases risk of falls and associated morbidities. CONCLUSIONS: The blue light hazard is misused as a marketing stratagem to alarm people into using spectacles and IOLs that restrict blue light. Blue light loss is permanent for pseudophakes with blue-blocking IOLs. Blue light hazard misrepresentation flourishes despite absence of proof that environmental light exposure or cataract surgery causes AMD or that IOL chromophores provide clinical protection. Blue-filtering chromophores suppress blue light critical for good mental and physical health and for optimal scotopic and mesopic vision.

DENOISING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY VOLUMETRIC SCANS USING A DEEP LEARNING MODEL.

PURPOSE: To evaluate the use of a deep learning noise reduction model on swept source optical coherence tomography volumetric scans. METHODS: Three groups of images including single-line highly averaged foveal scans (averaged images), foveal B-scans from volumetric scans using no averaging (unaveraged images), and deep learning denoised versions of the latter (denoised images) were obtained. We evaluated the potential increase in the signal-to-noise ratio by evaluating the contrast-to-noise ratio of the resultant images and measured the multiscale structural similarity index to determine whether the unaveraged and denoised images held true in structure to the averaged images. We evaluated the practical effects of denoising on a popular metric of choroidal vascularity known as the choroidal vascularity index. RESULTS: Ten eyes of 10 subjects with a mean age of 31 years (range 24-64 years) were evaluated. The deep choroidal contrast-to-noise ratio mean values of the averaged and denoised image groups were similar (7.06 vs. 6.81, P = 0.75), and both groups had better maximum contrast-to-noise ratio mean values (27.65 and 46.34) than the unaveraged group (14.75; P = 0.001 and P < 0.001, respectively). The mean multiscale structural similarity index of the average-denoised images was significantly higher than the one from the averaged--unaveraged images (0.85 vs. 0.61, P < 0.001). Choroidal vascularity index values from averaged and denoised images were similar (71.81 vs. 71.16, P = 0.554). CONCLUSION: Using three different metrics, we demonstrated that the deep learning denoising model can produce high-quality images that emulate, and may exceed, the quality of highly averaged scans.

SUBRETINAL DRUSENOID DEPOSITS AND SOFT DRUSEN: Are They Markers for Distinct Retinal Diseases?

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.

ACUTE FOVEALITIS.

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.