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.

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.

The Short-term Effects of Artificial Tears on the Tear Film Assessed by a Novel High-Resolution Tear Film Imager: A Pilot Study.

PURPOSE: The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device. METHODS: The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant. RESULTS: For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA (P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline. CONCLUSIONS: We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient.

A Remote Consult Retinal Artery Occlusion Diagnostic Protocol.

PURPOSE: To report a novel protocol for diagnosis of retinal artery occlusions at the point of care using OCT and a remote consult model. DESIGN: Retrospective case series and evaluation of a diagnostic test or technology. PARTICIPANTS: Adult patients who presented with painless monocular vision loss and were diagnosed with a nonarteritic retinal artery occlusion. METHODS: OCT machines were placed in the stroke center or emergency department at 3 hospitals within our health system. Patients who presented with painless monocular vision loss were evaluated by the stroke neurology service and an OCT was acquired. The images were interpreted remotely by the retina service. An in-house ophthalmology consult was not required to make the final treatment decision. Eligible patients were treated with intra-arterial tissue plasminogen activator (IA-tPA). Patients were followed by ophthalmology during their admission when an in-house consultation service was available or otherwise evaluated immediately after discharge. MAIN OUTCOME MEASURES: Visual acuity (VA) before and after treatment with IA-tPA; time from last known well (LKW) to treatment; and time from presentation to treatment. RESULTS: In the first 18 months since the protocol went live, 59 patients were evaluated. Twenty-five patients (42%) had a confirmed retinal artery occlusion based on OCT and follow-up examination. Ten patients were eligible for treatment, and 9 patients received treatment with IA-tPA. There was a statistically significant improvement in mean VA from logarithm of the minimum angle of resolution (logMAR) 2.14 to logMAR 0.7 within 24 hours after treatment (P = 0.0001) and logMAR 1.04 after 4 weeks (P = 0.01). Clinically significant improvement was noted in 66% of patients within 24 hours and maintained through 1 month in 56% of all treated patients. The mean time to treatment from LKW was 543 minutes and from presentation at the stroke center was 146 minutes. CONCLUSIONS: We report the successful implementation of a remote consult protocol using point-of-care automated OCT. This novel paradigm demonstrates the potential utility of remote consult services for the diagnosis of time-sensitive ophthalmic emergencies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Internal Carotid Artery Stenosis and Ipsilateral Subretinal Drusenoid Deposits.

Purpose: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are strongly associated with vasculopathies such as myocardial infarction and ischemic stroke. This study evaluates ischemic stroke subjects for SDDs to determine whether ocular hypoperfusion from internal carotid artery (ICA) stenosis is associated with ipsilateral SDDs. Methods: A cross-sectional study at Mount Sinai Hospital recruited 39 subjects with ischemic stroke (aged 52-90; 18 women, 21 men); 28 completed all study procedures. Computed tomography (CT) of the head and neck evaluated 54/56 ICAs for stenosis criteria: none (n = 33), mild (n = 12), moderate (n = 3), severe (n = 3), and complete (n = 3). Spectral-domain optical coherence tomography (SD-OCT) scans were read to consensus by two masked graders for soft drusen, SDDs and choroidal thickness (CTh; choroidal thinning = CTh < 250 µm). Univariate testing was done with Fisher's exact test. Multivariate logistic regression models tested age, gender, and ICA stenosis as covariates. Results: Moderate or more ICA stenosis (≥50%-69%) was significantly associated with ipsilateral choroidal thinning (P = 0.021) and ipsilateral SDDs (P = 0.005); the latter were present distal to six of nine stenosed ICAs versus five of 33 normal ICAs. Mild ICA stenosis (≥1%-49%) was not significantly associated with ipsilateral SDDs. Multivariate regression found that older age (P = 0.015) and moderate or more ICA stenosis (P = 0.011) remained significant independent risks for ipsilateral SDDs. Conclusions: At least moderate ICA stenosis (≥50%-69%) is strongly associated with ipsilateral SDDs and choroidal thinning, supporting downstream ophthalmic artery and choroidal hypoperfusion from ICA stenosis as the mechanism for SDD formation. SDDs may thus serve as sensitive biomarkers for ischemic stroke and other vascular diseases.

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.

LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

Effects of Toll-like receptor 1 and 2 agonist Pam3CSK4 on uveal melanocytes and relevant experimental mouse model.

Pam3CSK4 activates Toll-like receptors 2 and 1 (TLR1/2), which recognize mainly molecules from gram-positive pathogens. The effect of Pam3CSK4 on various cytokine and chemokine expression in cultured human uveal melanocytes (UM) has not been studied systematically. The purpose of this study was to investigate the mechanistic expressions of seven cytokines and chemokines of interleukin- (IL-) 6, IL-10, MCP-1 (CCL-2), CXCL-1 (GRO-α), CXCL-8 (IL-8), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) in UM. These cytokines are reported to be increased in intraocular fluids or tissues of the patients with endophthalmitis and non-infectious uveitis, as well as in various experimental animal uveitic models in the literature. Flow cytometry was used to measure the effects of Pam3CSK4 on the expression of TLR1/2 in UM. ELISA and Real-time PCR analysis were used to estimate the ability of Pam3CSK4 to elevate these cytokines and chemokines levels in conditioned media and cell lysates of UM, respectively. Flow cytometry measured and compared the phosphorylated MAPK pathway and activated NF-κB signals pathway in UM, treated with and without Pam3CSK4. ELISA analysis tested the effect of various signal inhibitors (ERK1/2, JNK1/2, p38 and NF-κB) on Pam3CSK4-induced IL-6 levels in cultured UM. The role of TLR2 in Pam3CSK4-induced acute anterior uveitis in experimental mouse model was tested in TLR2 knockout (TLR2 KO) mice and their wild-type C57Bl/6 controls. Pam3CSK4 increased the expression of TLR1/2 proteins in cultured UM. Pam3CSK4 significantly elevated the IL-6, MCP-1, CXCL-1, CXCL-8 protein, and mRNA levels in cultured UM, but not IL-10, TNF-α, or IFN-γ. Pam3CSK4 activated NF-κB, ERK, JNK, and p38 expression. Pam3CSK4-induced expression of IL-6 was decreased by NF-κB, ERK, INK, and p38 inhibitors; especially the NF-κB inhibitor, which can completely block the IL-6 stimulation. Intravitreal injection of Pam3CSK4 induced acute anterior uveitis in C57Bl/6 mice, this effect was significantly reduced in TLR2 KO mice. TLR1/2 plays an important role against invading pathogens, especially gram-positive bacteria; but an excessive reaction to molecules from gram-positive bacteria may promote non-infectious uveitis. UM can produce IL-6, MCP-1, CXCL-1, and CXCL-8, and are one of the target cells of TNF-α and IFN-γ. TLR-2 inhibitors might have a beneficial effect in the treatment of certain types of uveitis and other ocular inflammatory-related diseases and warrant further investigation.

Modified Endolaser Instrument for Chandelier Scleral Buckling.

Purpose: To report a new modification of an illuminated endolaser to facilitate safe endophotocoagulation during chandelier-assisted scleral buckling surgery. Methods: This case series comprised phakic patients with rhegmatogenous retinal detachments (RRDs) who had primary scleral buckling with chandelier endoillumination, external drainage, and endophotocoagulation using the modified endolaser instrument. Results: All 6 patients had successful outcomes after primary scleral buckling for RD repair without significant intraoperative or postoperative complications. Conclusions: The new modified endolaser instrument can be safely used in a nonvitrectomized eye during chandelier scleral buckling.

Assessing the Sensitivity of OCT-A Retinal Vasculature Metrics.

Purpose: The purpose of this study was to examine the sensitivity of quantitative metrics of the retinal vasculature derived from optical coherence tomography angiography (OCT-A) images. Methods: Full retinal vascular slab OCT-A images were obtained from 94 healthy participants. Capillary loss, at 1% increments up to 50%, was simulated by randomly removing capillary segments (1000 iterations of randomized loss for each participant at each percent loss). Thirteen quantitative metrics were calculated for each image: foveal avascular zone (FAZ) area, vessel density, vessel complexity index (VCI), vessel perimeter index (VPI), fractal dimension (FD), and parafoveal intercapillary area (PICA) measurements with and without the FAZ (mean PICA, summed PICA, PICA regularity, and PICA standard deviation [PICA SD]). The sensitivity of each metric was calculated as the percent loss at which 80% of the iterations for a participant fell outside of two standard deviations from the sample's normative mean. Results: The most used OCT-A metrics, FAZ area and vessel density, were not significantly different from normative values until 27.69% and 16.00% capillary loss, respectively. Across the remaining metrics, metric sensitivity ranged from 6.37% (PICA SD without FAZ) to 39.78% (Summed PICA without FAZ). Conclusions: The sensitivity of vasculature metrics for detecting random capillary loss varies substantially. Further efforts simulating different patterns of capillary loss are needed for comparison. Additionally, mapping the repeatability of metrics over time in a normal population is needed to further define metric sensitivity. Translational Relevance: Quantitative metrics vary in their ability to detect vascular abnormalities in OCT-A images. Metric choice in screening studies will need to balance expected capillary abnormalities and the quality of the OCT-A images being used.

Optical coherence tomography angiography in diabetic retinopathy.

There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.

3-D OCT imaging of hyalocytes in partial posterior vitreous detachment and vaso-occlusive retinal disease.

Purpose: To describe the spatial distribution and morphologic characteristics of macrophage-like cells called hyalocytes in the posterior vitreous cortex of a patient with unilateral partial posterior vitreous detachment (PVD) using coronal plane en face optical coherence tomography (OCT). Observations: A 54-year-old male with sickle cell disease (HbSC genotype) presented with a partial PVD in one eye. Rendered volumes of a slab extending from 600 µm to 3 µm anterior to the inner limiting membrane (ILM) revealed hyperreflective foci in the detached posterior vitreous cortex suspended anterior to the macula, likely representing hyalocytes. In the fellow eye without PVD, hyperreflective foci were located 3 µm anterior to the ILM. The morphology of the cells in the eye with PVD varied between a ramified state with multiple elongated processes and a more activated state characterized by a plump cell body with fewer retracted processes. In the same anatomical location, the hyperreflective foci were 10-fold more numerous in the patient with vaso-occlusive disease than in an unaffected, age-matched control. Conclusions and Importance: Direct, non-invasive, and label-free techniques of imaging cells at the vitreoretinal interface and within the vitreous body is an emerging field. The findings from this case report suggest that coronal plane en face OCT can be used to provide a detailed and quantitative characterization of cells at the human vitreo-retinal interface in vivo. Importantly, this case report demonstrates that 3D-OCT renderings can enhance visualization of these cells in relation to the ILM, which may provide clues concerning the identity and contribution of these cells to the pathogenesis of vitreo-retinal diseases.

Posterior vitreous cortex hyalocytes visualization in asymmetric pigmented paravenous chorioretinal atrophy (PPCRA) using en face OCT.

Purpose: Pigmented paravenous chorioretinal atrophy (PPCRA) is a rare retinal disease with inflammatory or infectious associations affecting the retinal pigment epithelium (RPE) and choriocapillaris. While the clinical manifestations and imaging findings are well-documented in the literature, no reports exist describing potential biomarkers of intraocular inflammation or ischemia in this condition, such as the presence of posterior vitreous cortex hyalocytes. Observations: We report a case of a 26-year-old female who presented with progressive peripheral vision loss in both eyes over one year. Dilated fundus examination revealed bilateral, asymmetric bone-spicule pigmentary changes along the retinal veins, which appeared more advanced in the left eye. Optical coherence tomography (OCT) revealed the presence of numerous hyalocytes in both eyes 3 µm anterior to the inner limiting membrane (ILM). The morphology of the hyalocytes differed between the two eyes, suggesting different levels of activation related to the stage of the disease. Specifically, the left eye, with more advanced disease, exhibited hyalocytes with multiple elongated processes consistent with a quiescent state, whereas the right eye, with the less advanced disease state, exhibited amoeboid-appearing hyalocytes suggestive of more active inflammation. Conclusions: This case illustrates how hyalocyte morphology may reflect the underlying activity of an indolent retinal degeneration and provide a useful biomarker of disease progression.

Imaging vitreous cortex hyalocyte response to paracentral acute middle maculopathy (PAMM) using En Face OCT.

INTRODUCTION: Vitreous cortex hyalocytes (VCH) are resident macrophage cells that provide immunosurveillance, respond to tissue injury and inflammation, and help maintain the transparency of the media. In this case report we demonstrate the use of en face optical coherence tomography (OCT) to image VCH in vivo in a patient presenting with PAMM secondary to antiphospholipid syndrome. CASE DESCRIPTION: A 38-year-old female with no known medical history presented with complaints of visual disturbances in the right eye. OCT revealed hyperreflective bands in the IPL and INL nasal to the fovea. A diagnosis of PAMM was made. Work-up revealed elevated titers of antiphospholipid antibodies. En face OCT revealed a decline in the inflammatory activation over a seven-month period as evidenced by changes in VCH distribution and morphology. CONCLUSIONS: Our findings suggest that monitoring changes in the distribution and morphology of VCH could have a potential clinical utility for assessing disease severity, predicting recovery, and early recognition of treatment response in various inflammatory ocular pathologies such as PAMM.

Insights into Sickle Cell Disease through the Retinal Microvasculature: Adaptive Optics Scanning Light Ophthalmoscopy Correlates of Clinical OCT Angiography.

Purpose: Clinical OCT angiography (OCTA) of the retinal microvasculature offers a quantitative correlate to systemic disease burden and treatment efficacy in sickle cell disease (SCD). The purpose of this study was to use the higher resolution of adaptive optics scanning light ophthalmoscopy (AOSLO) to elucidate OCTA features of parafoveal microvascular compromise identified in SCD patients. Design: Case series of 11 SCD patients and 1 unaffected control. Participants: A total of 11 eyes of 11 SCD patients (mean age, 33 years; range, 23-44; 8 female, 3 male) and 1 eye of a 34-year-old unaffected control. Methods: Ten sequential 3 × 3 mm parafoveal OCTA full vascular slab scans were obtained per eye using a commercial spectral domain OCT system (Avanti RTVue-XR; Optovue). These were used to identify areas of compromised perfusion near the foveal avascular zone (FAZ), designated as regions of interest (ROIs). Immediately thereafter, AOSLO imaging was performed on these ROIs to examine the cellular details of abnormal perfusion. Each participant was imaged at a single cross-sectional time point. Additionally, 2 of the SCD patients were imaged prospectively 2 months after initial imaging to study compromised capillary segments across time and with treatment. Main Outcome Measures: Detection and characterization of parafoveal perfusion abnormalities identified using OCTA and resolved using AOSLO imaging. Results: We found evidence of abnormal blood flow on OCTA and AOSLO imaging among all 11 SCD patients with diverse systemic and ocular histories. Adaptive optics scanning light ophthalmoscopy imaging revealed a spectrum of phenomena, including capillaries with intermittent blood flow, blood cell stasis, and sites of thrombus formation. Adaptive optics scanning light ophthalmoscopy imaging was able to resolve single sickled red blood cells, rouleaux formations, and blood cell-vessel wall interactions. OCT angiography and AOSLO imaging were sensitive enough to document improved retinal perfusion in an SCD patient 2 months after initiation of oral hydroxyurea therapy. Conclusions: Adaptive optics scanning light ophthalmoscopy imaging was able to reveal the cellular details of perfusion abnormalities detected using clinical OCTA. The synergy between these clinical and laboratory imaging modalities presents a promising avenue in the management of SCD through the development of noninvasive ocular biomarkers to prognosticate progression and measure the response to systemic treatment.

Hyalocytes in proliferative vitreo-retinal diseases.

Introduction: Hyalocytes are sentinel macrophages residing within the posterior vitreous cortex anterior to the retinal inner limiting membrane (ILM). Following anomalous PVD and vitreoschisis, hyalocytes contribute to paucicellular (vitreo-macular traction syndrome, macular holes) and hypercellular (macular pucker, proliferative vitreo-retinopathy, proliferative diabetic vitreo-retinopathy) diseases. Areas covered: Studies of human tissues employing dark-field, phase, and electron microscopy; immunohistochemistry; and in vivo imaging of human hyalocytes. Expert opinion: Hyalocytes are important in early pathophysiology, stimulating cell migration and proliferation, as well as subsequent membrane contraction and vitreo-retinal traction. Targeting hyalocytes early could mitigate advanced disease. Ultimately, eliminating the role of vitreous and hyalocytes may prevent proliferative vitreo-retinal diseases entirely.

Multimodal Imaging and Macular Hyalocyte Count in a Patient with Acute Macular Neuroretinopathy.

Though rare, acute macular neuroretinopathy is a well-described clinical entity. We report for the first time a detailed analysis of macular hyalocyte count and morphology during the acute phase of acute macular neuroretinopathy. We present a case of a 19-year-old man with bilateral acute onset paracentral scotomas in the setting of an antecedent viral infection. Multimodal imaging demonstrated classic features of acute macular neuroretinopathy. Further analysis revealed increased macular hyalocyte count and an activated hyalocyte morphology during the acute phase of the disease course. Multimodal imaging not only allows for greater confidence in a diagnosis and prognosis but also helps to shed light on underlying pathophysiology. The new clinical capability of monitoring cellular behavior, such as hyalocyte count and morphology, in physiological and pathological conditions may prove useful as biomarkers of early disease activity or response to therapy.

Efficacy of CRISPR-Based Gene Editing in a Sickle Cell Disease Patient as Measured through the Eye.

Sickle cell disease (SCD) exists on a phenotypic spectrum with variable genetic expressivity, making it difficult to assess an individual patient's risk of complications at any particular point in time. Current and emerging SCD treatments, including CRISPR-based gene editing, result in a variable proportion of affected red blood cells (RBCs) still vulnerable to sickling. Clinical serological indicators of disease such as hemoglobin, indirect bilirubin, and reticulocyte count and clinical metrics including number of emergency department visits and hospitalizations over time often fall short in their ability to objectively quantify ischemic disease activity and efficacy of treatments. Clearly, better clinical biomarkers are needed. The rapidly developing field of oculomics leverages the transparent nature of the ocular tissue to directly study the retinal microvasculature in order to characterize the status of systemic diseases. In this case report, we demonstrate the ability of optical coherence tomography angiography (OCT-A) to detect and measure micro-occlusive events within the retinal capillary bed before and after RBC exchange transfusion and following CRISPR-based gene editing, as an indicator of systemic ischemic disease activity and measure of treatment efficacy. The implications of these findings are discussed.

"Persistence of Memory" - Multimodal imaging of delayed sympathetic ophthalmia.

Purpose: To describe a case of late post-surgical sympathetic ophthalmia documented with multimodal imaging. Observations: A 74-year-old male presented to the urgent care of the New York Eye and Ear Infirmary with blurry vision and discomfort in his left eye for three weeks. His vision was 20/50, with intraocular pressure of 13 mmHg, and slit lamp examination was significant for conjunctival congestion, 1+ anterior segment cell and flare, and diffuse keratic precipitates. His right eye was no light perception with a condensed hyphema, intraocular lens and inferonasal tube. His medical history included coronary artery bypass, prostate cancer, hyperlipidemia, and hypertension. His ocular history included blunt trauma to the right eye at age 11 with development of a traumatic macular hole and later rhegmatogenous retinal detachment at age 53, repaired with multiple vitreoretinal procedures. He developed glaucoma in the right eye and was treated with a tube shunt and ultimately transscleral cyclophotocoagulation (TSCPC) 7 years later, 13 years prior to his presentation of the left eye. Dilated fundus examination of his left eye revealed diffuse chorioretinal folds in the macula without any discrete chorioretinal lesions. Ultrasound of the right showed serous macular detachments with scleral thickening. Presumptive diagnosis of sympathetic ophthalmia was made and oral corticosteroid therapy was initiated. Subsequent SD-OCT and en-face OCT-A demonstrated Dalen-Fuchs nodules within the macula underlying areas of resolved serous detachment, after 6 weeks of oral steroids and initiation of immunomodulatory therapy (IMT). Conclusions: Sympathetic ophthalmia may rarely present with very delayed onset, and TSCPC is an uncommon inciting event. These patients may develop serous detachment, choroidal folds and inflammatory nodules identifiable on exam and multimodal imaging, which can resolve when treated appropriately. OCT-A may provide utility in monitoring response to immunosuppressive treatment in these patients.

Imaging of vitreous cortex hyalocyte dynamics using non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy in human subjects.

Vitreous cortex hyalocytes are resident macrophage cells that help maintain the transparency of the media, provide immunosurveillance, and respond to tissue injury and inflammation. In this study, we demonstrate the use of non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy (AOSLO) to non-invasively visualize the movement and morphological changes of the hyalocyte cell bodies and processes over 1-2 hour periods in the living human eye. The average velocity of the cells 0.52 ± 0.76 µm/min when sampled every 5 minutes and 0.23 ± 0.29 µm/min when sampled every 30 minutes, suggesting that the hyalocytes move in quick bursts. Understanding the behavior of these cells under normal physiological conditions may lead to their use as biomarkers or suitable targets for therapy in eye diseases such as diabetic retinopathy, preretinal fibrosis and glaucoma.