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.

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.

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.

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.

High Myopia Prevalence across Racial Groups in the United States: A Systematic Scoping Review.

High myopia is a significant public health issue globally and in the United States (US), where it affects ~4% of the population or 13 million people. This is a potentially blinding condition, but complications can be prevented with early intervention in childhood. Several countries have developed robust data on high myopia, but the United States' data on high myopia remains lacking. Further, underrepresented populations are at particular risk of complications due to reduced access to optometric and ophthalmic care. We performed a systematic scoping review of population-based studies that investigated the prevalence of high myopia across racial and ethnic groups in the US to identify the impact of high myopia on underrepresented communities. Only four studies were identified that met inclusion criteria, which highlights the need to further investigate the topic in the United States. The prevalence of high myopia ranged from a low of 1.8% among Hispanic populations to a high of 11.8% among Chinese populations. Our study demonstrated a paucity of high myopia data in the United States and variable rates of high myopia depending on the time and location of each study. More complete prevalence data will help identify opportunities for community-based interventions to prevent debilitating and blinding complications of high myopia.

Intravitreal dexamethasone insert in diabetic macular edema super-refractory to anti-vascular endothelial growth factor therapy.

BACKGROUND: Some patients with diabetic macular edema (DME) fail to completely respond to anti-vascular endothelial growth factor (VEGF) therapy. These patients have a high treatment burden in the absence of significant improvement. We investigate the role of intravitreal dexamethasone insert (IDI) in eyes with super-refractory DME. METHODS: A non-randomized interventional study was performed among eyes with super-refractory DME refractory to anti-VEGF therapy. Eyes were treated with IDI after failing clinical response to anti-VEGF, with a minimum of 15 prior. Failure to respond was defined as failure of vision to improve at least one line on Snellen Acuity chart, central subfield thickness (CST) greater than 320 µm, or failure of CST to improve by 10% or more. Eyes with glaucoma or prior uncontrolled steroid-responsive ocular hypertension were excluded. Patient outcomes were analyzed at weeks 6, 12, 24, and year 1. RESULTS: Six eyes of four patients were identified. All patients had failed aflibercept. The mean number of prior anti-VEGF injections was 34.5. Eyes received an average of 2.92 dexamethasone injections per person-year (PY) and required breakthrough anti-VEGF injection at 1.95/PY. Mean pre-treatment visual acuity was 0.475 LogMAR, improving to 0.342 at week 6, and 0.375 at 1 year. Mean CST pre-injection was 386.5 mm, improving to 315 mm at 1 year. No glaucoma developed. CONCLUSIONS: Intravitreal dexamethasone insert appears effective in eyes with super-refractory DME. IDI resulted in excellent anatomic improvement on SD-OCT as well as modest visual improvement. Injection burden was reduced in those who may otherwise receive years of monthly treatments.

Fundus albipunctatus photoreceptor microstructure revealed using adaptive optics scanning light ophthalmoscopy.

PURPOSE: Fundus albipunctatus is an inherited cause of congenital stationary night blindness. The objective of this report is to describe structural changes occurring in a macular phenotype of a novel RDH5 mutation producing fundus albipunctatus using high-resolution in vivo imaging. A 62-year-old male with longstanding night blindness underwent imaging and genetic evaluation. High-resolution images of the photoreceptor mosaic were compared to those of a healthy subject. Results of a comprehensive ophthalmic evaluation and genetic testing with imaging including fundus photography, spectral-domain optical coherence tomography (OCT), fluorescein angiography (FA), OCT angiography (OCT-A), and adaptive optics scanning light ophthalmoscopy (AOSLO) are described. OBSERVATIONS: The patient presented with visual acuity of 20/25 in both eyes and longstanding poor dark adaptation. Anterior segment examination was unremarkable. Fundoscopy revealed well circumscribed bilateral perifoveal mottling and atrophy in both eyes. Discrete white-yellow flecks were present beyond the vascular arcades extending to the far periphery. Genetic testing revealed a novel compound heterozygous RDH5 mutation (c.388C > T, p.Gln130*; c.665T > C, p.Leu222Pro). OCT demonstrated perifoveal photoreceptor and outer retinal irregularities, which corresponded to a window defect with late staining on FA. OCT-A demonstrated normal retinal vasculature with patchy areas of non-perfusion in the choriocapillaris. Macular abnormalities in both eyes were imaged using AOSLO to assess cone and rod photoreceptor architecture. While clinical features are consistent with a primary rod disorder, confocal AOSLO showed a paucity of normal cones with a small spared central island in both eyes. Rods appeared larger and more irregular throughout the macula. Non-confocal split detection AOSLO imaging revealed the presence of cone inner segments in dark regions of confocal imaging, indicating some degree of photoreceptor preservation. CONCLUSIONS AND IMPORTANCE: The AOSLO imaging of this particular macular phenotype of fundus albipunctatus demonstrates some of the structural photoreceptor abnormalities that occur in this condition, adding insight to the variable presentation of RDH5 retinopathy. The presence of preserved inner segment architecture suggests the possibility that gene therapy could play a future role in treating this condition.

Intra-Arterial Tissue Plasminogen Activator for Central Retinal Artery Occlusion.

PURPOSE: To investigate the benefit of early intra-arterial tissue plasminogen activator (IAT) for treatment of central retinal artery occlusion (CRAO). PATIENTS AND METHODS: Fifteen eyes of 15 patients presenting with acute CRAO were included in this retrospective consecutive interventional case series. Patients were excluded if treatment with IAT was not initiated within 12 hours. The diagnosis was confirmed by an ophthalmologist. IAT was performed via a transfemoral arterial approach. Tissue plasminogen activator (tPA) was infused into the ophthalmic artery in aliquots up to 3mg to a maximum of 22mg. Paracentesis was done at the ophthalmologist's discretion. The primary outcome measure was visual acuity after three weeks. Adverse events were recorded during treatment and follow-up visits. RESULTS: After treatment with IAT, there was a statistically significant improvement in visual acuity, with a mean change of -0.76 (SD 0.91; range -2.4 to 0.85) logMAR (p=0.006). Vision improved by 3 or more lines in 53%, and of these, the mean Snellen visual acuity improvement was >6 lines. Notably, 4 patients (27%) improved from CF or worse to 20/80 or better. The mean dose of tPA used was 17mg and the mean time to treatment was 8.83 hours (range: 5.5 to 12 hours). There were no statistically significant differences based on time to treatment, dose of tPA, or use of a paracentesis. No major adverse events were recorded. CONCLUSION: IAT was safe and showed significant visual improvement in this small uncontrolled study. Larger studies and efforts to decrease time to treatment should be initiated to optimize outcomes.

Current topics in acute stroke care: part 2: central retinal artery occlusion: a stroke of the eye.

This review discusses central retinal artery occlusion.

Prompt vitrectomy for management of endophthalmitis in setting of unexposed glaucoma drainage implant.

PURPOSE: To highlight a rare case of fulminant endophthalmitis in the late post-operative stage after glaucoma drainage device implantation without evidence of device exposure, and to share the unique management that resulted in successful restoration of vision and intraocular pressure control. OBSERVATIONS: Endophthalmitis after glaucoma drainage implantation (GDI) is a rare complication most often associated with exposure of the device. Management options are limited, but removal of GDI is a common approach in the setting of an exposed implant. Visual acuity outcomes are often significantly reduced despite adequate treatment. There is little in the existing literature about management of late-onset endophthalmitis in the setting of a GDI without implant exposure. Here we present such a case that was successfully managed by prompt pars plana vitrectomy and removal of tube from the anterior chamber with subsequent re-insertion and patch graft. Our case results in a restoration of baseline visual acuity and IOP control at 7 months follow up. CONCLUSIONS AND IMPORTANCE: Endophthalmitis occurring after GDI implantation is a challenging complication to manage. Many physicians resort to removal of device for treatment, and a majority would treat initially with intravitreal antibiotic injection of antibiotics rather than prompt pars plana vitrectomy. This article provides a different approach that avoids removal of the device.

PROGNOSTIC INDICATORS OF VISUAL ACUITY AFTER OPEN GLOBE INJURY AND RETINAL DETACHMENT REPAIR.

PURPOSE: To identify prognostic indicators of postoperative visual acuity and retinal detachment (RD) in open globe injuries. METHODS: Retrospective review of 50 adult open globe injuries between September 2011 and March 2014. Hierarchical multivariable regression was used to evaluate relationships among injury characteristics, postoperative visual acuity, and RD after age adjustment. RESULTS: Mean participant age was 46.2 years, and mean follow-up was 1.2 years. Blunt trauma accounted for 58% of injuries (29/50), and the wound extended posteriorly into sclera in 64% of cases (32/50). The retinal detachment occurred in 40% of patients (20/50), 95% of whom had developed vitreous hemorrhage (19/20). Multivariable regression revealed that preoperative visual acuity (P = 0.0010), posterior wound extension (P = 0.022), and RD (P = 0.0038) independently predicted postoperative visual acuity. No other injury characteristic was related to postoperative visual acuity after adjustment for preoperative visual acuity. Vitreous hemorrhage predicted RD (P < 0.001), and further consideration of preoperative visual acuity and other variables did not improve model fit. Moreover, among patients who underwent RD repair (n = 13), earlier vitrectomy after vitreous hemorrhage diagnosis (≤12 days) was associated with fewer macula-off RDs (P = 0.018) and better postoperative visual acuity (P = 0.0055). CONCLUSION: Preoperative visual acuity, posterior wound extension, and RD significantly influenced postoperative visual acuity after open globe injury. Vitreous hemorrhage predicted RD, and prompt intervention after detection may improve visual outcomes.

Esophageal metastasis to the iris effectively palliated using stereotactic body radiation therapy and adjuvant intravitreal chemotherapy: case report and literature review.

We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient's symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris.

Modes and models of GABA(A) receptor gating.

Upon activation by agonist, the type A gamma-aminobutyric acid receptor (GABAR) 'gates', allowing chloride ions to permeate membranes and produce fast inhibition of neurons. There is no consensus kinetic model for the GABAR gating mechanism. We expressed human alpha(1)beta(1)gamma(2S) GABARs in HEK 293 cells and recorded single channel currents in the cell-attached configuration using various GABA concentrations (50-5000 microm). Closed and open events occurred individually and in clusters that had at least three different modes that were distinguishable by open probability (P(O)): High (P(O)= 0.73), Mid (P(O)= 0.50), and Low (P(O)= 0.21). We used a critical time to isolate shorter bursts of openings and to thus eliminate long-lived, desensitized events. Bursts from all three modes contained three closed and three open components. We employed maximum likelihood fitting, autocorrelation analysis and macroscopic current simulation to distinguish kinetic schemes. The 'core' gating scheme for most models contained two closed states that preceded an open state (C(1) C(2) O(1)). The two best-fitting models had a third closed state connected to C(1) and a second open state (O(2)) connected to C(2). The third open state, whose occupancy varied greatly between modes, could be connected either to O(2) or C(2). We estimated rate constants for two identical, independent GABA binding steps by globally fitting data across GABA concentrations ranging from 50 to 1000 microm. For the most highly ranked model the binding rate constants were: k(+)= 3 microm(-1) s(-1) and k(-)= 272 s(-1) (K(D)= 91 microm).