A smartphone intervention that enhances real-world memory and promotes differentiation of hippocampal activity in older adults.

The act of remembering an everyday experience influences how we interpret the world, how we think about the future, and how we perceive ourselves. It also enhances long-term retention of the recalled content, increasing the likelihood that it will be recalled again. Unfortunately, the ability to recollect event-specific details and reexperience the past tends to decline with age. This decline in recollection may reflect a corresponding decrease in the distinctiveness of hippocampal memory representations. Despite these well-established changes, there are few effective cognitive behavioral interventions that target real-world episodic memory. We addressed this gap by developing a smartphone-based application called HippoCamera that allows participants to record labeled videos of everyday events and subsequently replay, high-fidelity autobiographical memory cues. In two experiments, we found that older adults were able to easily integrate this noninvasive intervention into their daily lives. Using HippoCamera to repeatedly reactivate memories for real-world events improved episodic recollection and it evoked more positive autobiographical sentiment at the time of retrieval. In both experiments, these benefits were observed shortly after the intervention and again after a 3-mo delay. Moreover, more detailed recollection was associated with more differentiated memory signals in the hippocampus. Thus, using this smartphone application to systematically reactivate memories for recent real-world experiences can help to maintain a bridge between the present and past in older adults.

Spatial context scaffolds long-term episodic richness of weaker real-world autobiographical memories in both older and younger adults.

Remembering life experiences involves recalling not only what occurred (episodic details), but also where an event took place (spatial context), both of which decline with age. Although spatial context can cue episodic detail recollection, it is unknown whether initially recalling an event alongside greater reinstatement of spatial context protects memory for episodic details in the long term, and whether this is affected by age. Here, we analysed 1079 personally-experienced, real-world events from 29 older adults and 12 younger adults. Events were recalled first on average 6 weeks after they occurred and then again on average 24 weeks after they occurred. We developed a novel scoring protocol to quantify spatial contextual details and used the established Autobiographical Interview to quantify episodic details. We found improved recall of episodic details after a delay if those details had initially been recalled situated in greater spatial context. Notably, for both older and younger adults, this preservation was observed for memories initially recalled with low, but not high, numbers of episodic details, suggesting that spatial context aided episodic retrieval for memories that required more support. This work supports the notion that spatial context scaffolds detail-rich event recollection and inspires memory interventions that leverage this spatial scaffold.

Object-in-place Memory Predicted by Anterolateral Entorhinal Cortex and Parahippocampal Cortex Volume in Older Adults.

The lateral portion of the entorhinal cortex is one of the first brain regions affected by tau pathology, an important biomarker for Alzheimer disease. Improving our understanding of this region's cognitive role may help identify better cognitive tests for early detection of Alzheimer disease. Based on its functional connections, we tested the idea that the human anterolateral entorhinal cortex (alERC) may play a role in integrating spatial information into object representations. We recently demonstrated that the volume of the alERC was related to processing the spatial relationships of the features within an object [Yeung, L. K., Olsen, R. K., Bild-Enkin, H. E. P., D'Angelo, M. C., Kacollja, A., McQuiggan, D. A., et al. Anterolateral entorhinal cortex volume predicted by altered intra-item configural processing. Journal of Neuroscience, 37, 5527-5538, 2017]. In this study, we investigated whether the human alERC might also play a role in processing the spatial relationships between an object and its environment using an eye-tracking task that assessed visual fixations to a critical object within a scene. Guided by rodent work, we measured both object-in-place memory, the association of an object with a given context [Wilson, D. I., Langston, R. F., Schlesiger, M. I., Wagner, M., Watanabe, S., & Ainge, J. A. Lateral entorhinal cortex is critical for novel object-context recognition. Hippocampus, 23, 352-366, 2013], and object-trace memory, the memory for the former location of objects [Tsao, A., Moser, M. B., & Moser, E. I. Traces of experience in the lateral entorhinal cortex. Current Biology, 23, 399-405, 2013]. In a group of older adults with varying stages of brain atrophy and cognitive decline, we found that the volume of the alERC and the volume of the parahippocampal cortex selectively predicted object-in-place memory, but not object-trace memory. These results provide support for the notion that the alERC may integrate spatial information into object representations.

Dissociable contributions of thalamic nuclei to recognition memory: novel evidence from a case of medial dorsal thalamic damage.

The thalamic nuclei are thought to play a critical role in recognition memory. Specifically, the anterior thalamic nuclei and medial dorsal nuclei may serve as critical output structures in distinct hippocampal and perirhinal cortex systems, respectively. Existing evidence indicates that damage to the anterior thalamic nuclei leads to impairments in hippocampal-dependent tasks. However, evidence for the opposite pattern following medial dorsal nuclei damage has not yet been identified. In the present study, we investigated recognition memory in NC, a patient with relatively selective medial dorsal nuclei damage, using two object recognition tests with similar foils: a yes/no (YN) test that requires the hippocampus, and a forced choice corresponding test (FCC) that is supported by perirhinal cortex. NC performed normally in the YN test, but was impaired in the FCC test. Critically, FCC performance was impaired only when the study-test delay period was filled with interference. We interpret these results in the context of the representational-hierarchical model, which predicts that memory deficits following damage to the perirhinal system arise due to increased vulnerability to interference. These data provide the first evidence for selective deficits in a task that relies on perirhinal output following damage to the medial dorsal nuclei, providing critical evidence for dissociable thalamic contributions to recognition memory.

Orbital floor fracture with entrapment: Imaging and clinical correlations in 45 cases.

Orbital floor fractures (OFF) with entrapment require prompt clinical and radiographic recognition for timely surgical correction. Correct CT radiographic interpretation of entrapped fractures can be subtle and thus missed. We reviewed the clinical, radiographic and intraoperative findings of 45 cases of entrapped OFF to correlate pre- and intraoperative findings with radiography. Retrospective review and statistical analysis of 45 patients with OFF using the chi squared and Kruskal-Wallis tests. Main outcome measures included patient demographics, clinical features, radiologic interpretation, intraoperative findings, and treatment outcomes. Twenty-one cases (47%) had radiologic evaluations of orbital CT scans that included commentary on possible entrapment. Intraoperatively, 16 (76%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 5 (24%) patients had incarceration of the orbital fat. Possibility of entrapment was not commented on in the radiology reports of the remaining 24 (53%) cases. Intraoperatively, 13 (54%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 11 (46%) patients had incarceration of the orbital fat. It is vital to assess the possibility of entrapment, especially in young patients, in the setting of OFF as a delay in diagnosis may lead to persistent diplopia, disfigurement, or bradycardia. Most radiology reports did not mention the possibility of entrapment in this cohort. A key concept is that entrapment occurs when any orbital tissue (muscle or fat) is trapped in the fracture site.

Repeatability of selective laser trabeculoplasty for open-angle glaucoma.

BACKGROUND: To analyze the results of repeat selective laser trabeculoplasty (SLT). INCLUSION CRITERIA: participants with primary or secondary open-angle glaucoma (excluding uveitic) who had undergone SLT 360° (SLT 1) with diminution of response over time followed by repeat SLT 360° (SLT 2). Six months of follow-up were required and at least 6 months in between SLT 1 and 2. The main outcome measures were IOP reduction at 6 and 12 months and a comparison of the response between SLT 1 and 2. RESULTS: One hundred thirty-seven patients met the inclusion criteria. If only one eye had repeat treatment, that eye was chosen; if both eyes qualified, one was chosen at random. The baseline intraocular pressure (IOP) for SLT 1 = 20.3+/- 5.2 mmHg and SLT 2 = 19.4 +/- 5.0 was reduced to 16.4 +/- 3.9 and 16.7 +/- 4.7 at 1 year, respectively (p < .001). Medication use was not significantly changed, and was 2.2 +/- 1.2 at baseline for SLT 1 and 2.1 +/- 1.3 for SLT 2, and at 1 year was 1.9 +/- 1.3 and 2.2 +/- 1.2, respectively. A subanalysis of 62 patients matched for equivalent baselines showed a baseline IOP = 18.7 +/- 3.8 for SLT 1 and 18.7 +/- 3.5 for SLT 2, reduced to 16.0 +/- 4.3 and 15.3 +/- 3.8 at 1 year (p < .001). CONCLUSION: Repeat SLT laser (360-degree treatment, followed by a loss of effect over time, then a second 360-degree treatment) in this population resulted in IOP lowering similar to that of the initial treatment.

Emerging techniques for pathogen discovery in endophthalmitis.

PURPOSE OF REVIEW: Despite the inability to detect certain organisms and relatively low yield, microbial culture is the current gold standard for the diagnosis of most intraocular infections. Research on alternative molecular diagnostic methods has produced an array of strategies that augment and improve pathogen detection. This review summarizes the most recent literature on this topic. RECENT FINDINGS: The yield of traditional microbial culture has not improved since the Endophthalmitis Vitrectomy Study results were published 20 years ago. Advances in PCR methods have enabled quantification of pathogen load and screening for multiple organisms at once. More recently, deep sequencing techniques allow highly sensitive detection of any DNA-based life form in a specimen. This offers the promise of not only improved detection of traditional organisms but can also identify organisms not previously associated with endophthalmitis. SUMMARY: Molecular diagnostic methods enhance the results of microbial culture and may become the new standard in the diagnosis of intraocular infections.

Prognostic Utility of Whole-Genome Sequencing and Polymerase Chain Reaction Tests of Ocular Fluids in Postprocedural Endophthalmitis.

PURPOSE: To associate detection of potential pathogen DNA in endophthalmitis with clinical outcomes. DESIGN: Prospective cohort study. METHODS: Patients in whom endophthalmitis was diagnosed following an intraocular procedure were recruited. Clinical outcome data from baseline, week-1, month-1, and month-3 visits were collected. Intraocular biopsy samples were cultured by standard methods. Quantitative polymerase chain reaction (qPCR) was performed for specific pathogens and whole-genome sequencing (WGS). RESULTS: A total of 50 patients (mean age 72 years old; 52% male) were enrolled. Twenty-four cases were culture-positive and 26 were culture-negative. WGS identified the cultured organism in 76% of culture-positive cases and identified potential pathogens in 33% of culture-negative cases. Month-1 and -3 visual acuities did not vary by pathogen-positive versus pathogen-negative cases as detected by either culture or WGS. Visual outcomes of Staphylococcus epidermidis endophthalmitis were no different than those of pathogen-negative cases, whereas the patients infected with other pathogens showed worse outcome. Higher baseline bacterial DNA loads of bacteria other than those of S epidermidis detected by WGS were associated with worse month-1 and -3 visual acuity, whereas the S epidermidis loads did not appear to influence outcomes. Torque teno virus (TTV) and Merkel cell polyomavirus (MCV) were detected by qPCR in 49% and 19% of cases, respectively. Presence of TTV at presentation was associated with a higher rate of secondary pars plana vitrectomy (P = .009) and retinal detachment (P = .022). CONCLUSIONS: The presence and higher load of bacteria other than S epidermidis detected by WGS or DNA from TTV by qPCR in ocular fluids is associated with worse outcomes in post-procedure endophthalmitis.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: Optical coherence tomography angiography (OCTA) is a novel technology that uses motion contrast instead of dye to generate angiographic images. Using several modalities of OCTA, the authors describe and compare changes observed in branch retinal vein occlusion. METHODS: A case series of three patients with OCTA imaging. RESULTS: Despite presenting at different time frames, the authors found common imaging findings consisting of vascular hypoperfusion, increased tortuosity, and telangiectasia in all their cases. Furthermore, macular edema and intraretinal fluid were noted on the en-face angiograms. The extent of vascular and structural alterations could clearly be delineated in superficial and deep retinal networks. However, fine capillary alterations were better appreciated on smaller-size scans. CONCLUSION: With the ability to noninvasively visualize vascular flow, OCTA could serve as a new diagnostic tool for current ophthalmic research and clinical practice. Such findings can help supplement other imaging modalities in establishing a diagnosis and monitoring disease progression over time. This would potentially be useful in regard to ischemic processes such as branch retinal vein occlusion and diseases affecting different layers of the retinal vasculature.

Ophthalmic Complications Associated with Direct Oral Anticoagulant Medications.

OBJECTIVE: To describe the clinical features and management of six patients with ocular complications associated with direct oral anticoagulants (DOACs). METHODS: The medical records of all adult patients known to be taking a DOAC and with an unusual bleeding event at a large tertiary referral center over a one-year period were reviewed. Patients with less than one-month follow-up were excluded. Data collection included relevant clinic notes, operative reports, surgical videos, and clinical images (fundus photography, optical coherence tomography, B-scan ultrasonography, and fluorescein angiography). RESULTS: Six eyes in six patients were identified with an unusual bleeding event associated with DOAC use. One patient was taking apixaban, two patients were taking dabigatran, and three patients were taking rivaroxaban. Two patients had large submacular hemorrhage (including one with vitreous hemorrhage breakthrough), three patients had vitreous hemorrhage, and one patient had recurrent hyphema. Presenting visual acuity ranged from 20/40 to light perception. Three individuals required therapeutic and/or diagnostic pars plana vitrectomy for vitreous hemorrhage. Final visual acuity ranged from 20/25 to count finger vision. The associated DOAC was permanently discontinued in two of the six cases. Follow-up was one to four months from onset of identified DOAC-related complication. CONCLUSIONS: DOAC use may be associated with ocular bleeding. Ophthalmologists should be aware of potential hemorrhagic complications and obtain consultation with primary providers regarding DOAC cessation guidelines.

Anterior chamber cholesterolosis in a patient with retinoblastoma.

Anterior chamber cholesterolosis is a rare phenomenon typically associated with non-neoplastic conditions such as hyphema or Coats disease; it has never been reported to be associated with intraocular malignancy. We report a case of anterior chamber cholesterolosis presenting in the setting of retinoblastoma and discuss clinical features relevant for its differentiation from Coats disease.

In Vivo Assessment of Macular Vascular Density in Healthy Human Eyes Using Optical Coherence Tomography Angiography.

PURPOSE: To quantify density of macular vascular networks over regions of interest in healthy subjects using optical coherence tomography angiography (OCTA). DESIGN: Prospective cross-sectional study. METHODS: Setting was the Retina and Oncology Services of Wills Eye Hospital. Subjects with no known systemic disease and without retinal pathology were included. OCTA was performed on a 3 × 3-mm region centered on the macula and en face angiograms of the superficial and deep vascular networks were acquired. Vascular density was calculated using an automated image thresholding method over regions of interest. Foveal and parafoveal vascular density were calculated. The differences between vascular networks, sexes, and fellow eyes and correlation between vascular density, signal strength, and age, as well as reproducibility of measurements, were evaluated. RESULTS: A total of 198 healthy eyes were imaged, from which 163 eyes of 122 subjects were included based on image quality criteria. In the parafoveal region, deep vascular density was significantly higher than the superficial (52% ± 2.4% vs 46% ± 2.2%; P < .001), whereas the opposite was found in the foveal region (27% ± 5.2% vs 32% ± 3.2%; P < .001). All vascular density measurements were statistically similar in fellow eyes and there was no sex difference (P > .05). There was a negative correlation between vascular density and age that persisted upon adjusting for signal strength. Vascular density measurements were highly correlated between separate imaging sessions with intraclass correlation coefficients of over 0.85 for all assessments. CONCLUSIONS: Calculation of vascular density using OCTA is a reproducible and noninvasive method to quantitate individual networks within the macula. Understanding normal values and their correlations could affect clinical evaluation of the macula in healthy patients and disease states.

Optical Coherence Tomography Angiography and En Face Optical Coherence Tomography Features of Paracentral Acute Middle Maculopathy.

PURPOSE: To characterize the optical coherence tomography (OCT) angiography, en face OCT, and microperimetry features of paracentral acute middle maculopathy in both the acute phase and after resolution, and to propose a classification of distinct subtypes of this entity. DESIGN: Retrospective observational case series. METHODS: Clinical histories, high-resolution digital color imaging, spectral-domain OCT images, fluorescein angiography, OCT angiography images, and en face OCT images of 16 patients with paracentral acute middle maculopathy were evaluated. Microperimetry was available in 6 patients. RESULTS: The most common referring diagnoses were isolated branch retinal arterial occlusion (5/16), combined central retinal vein and cilioretinal artery occlusion (4/16), and isolated central retinal vein occlusion (4/16). All patients demonstrated hyperreflective plaque-like lesions at the level of the inner nuclear layer on spectral-domain OCT, with no fluorescein angiographic correlate. OCT angiography demonstrated variable areas of capillary dropout within the superficial and deep retinal capillary plexi in these areas. En face OCT highlighted confluent areas of middle retina hyperreflectivity corresponding to these lesions. Three distinct en face OCT patterns were observed: arteriolar, fern-like, and globular. Microperimetry demonstrated relative scotomas mapping to the area of middle retinal hyperreflectivity seen on en face OCT. CONCLUSIONS: Paracentral acute middle maculopathy may be best evaluated with the use of en face OCT imaging, which corresponds to subjective and objective visual field defects. En face OCT appearance may be used to classify paracentral acute maculopathy into distinct subtypes.

Bilateral subinternal limiting membrane hemorrhage in benzene toxicity.

PURPOSE: To report the clinical and spectral domain optical coherence tomography findings in a patient with bilateral central vision loss and a history of exposure to polyamides. METHODS: The clinical presentation of the patient was documented with color fundus photographs and spectral domain optical coherence tomography. The patient was a 20-year-old male factory worker with no medical history who was initially admitted for workup of hematologic malignancy due to petechiae and fevers. RESULTS: Optical coherence tomography revealed bilateral hemorrhages in the subinternal limiting membrane space resembling Valsalva retinopathy. Complete blood count revealed pancytopenia and marked thrombocytopenia. CONCLUSION: Heavy exposure to benzene, a byproduct of the polyamide-curing process, is known to cause aplastic anemia. Accompanying thrombocytopenia may increase the risk of spontaneous subinternal limiting membrane hemorrhage.

The utility of routine tuberculosis screening in county hospital patients with uveitis.

BACKGROUND/AIM: To evaluate the utility of tuberculosis (TB) screening in diagnosing ocular TB in uveitis patients in a government-funded hospital. METHODS: The charts of 142 consecutive patients seen during August 2011-July 2012 at the Los Angeles County Hospital uveitis clinic were reviewed for manifestation/laterality of uveitis, purified protein derivative (PPD) test results, interferon γ release assay, chest x-ray, birthplace, treatment history and diagnosis. 'Presumed TB-uveitis' was diagnosed when patients had positive TB screening and favourable response to anti-TB therapy, and definite ocular TB when Mycobacterium tuberculosis' presence was demonstrated. Post-test probabilities were determined. RESULTS: TB screening was positive in 21.1%. Six patients were diagnosed with TB-related uveitis: one definite, four presumed and one systemic TB with uveitis. With regard to PPD positivity, being foreign-born was the only statistically significant factor with OR of 2.26 (95% CI 1.01 to 5.13; p<0.01) if born in Mexico and 4.90 (95% CI 1.74 to 13.83; p<0.01) if born in other foreign countries. The post-test probabilities of a positive PPD in a uveitis patient showed a 17.2% (overall) or 30.3% (foreign-born patients) chance of ocular TB. CONCLUSIONS: PPD skin test plays an important role in the diagnosis of TB-associated uveitis in high-risk groups, such as immigrants from TB endemic regions.

Intracameral injection of tissue plasminogen activator to treat severe postoperative fibrinous reaction in iridocorneal endothelial syndrome.

Iridocorneal endothelial (ICE) syndrome is a primary endothelial abnormality that can cause a spectrum of iris changes, corneal edema, and glaucoma. Glaucoma secondary to ICE is difficult to manage because of the inflammatory reaction and fibrosis it can cause. We present a case of postoperative fibrinous reaction following endoscopic cyclophotocoagulation in ICE that caused aqueous tube shunt occlusion and high intraocular pressure. The condition was successfully managed with tissue plasminogen activator.

Role of ultra-widefield fluorescein angiography in the management of uveitis.

OBJECTIVE: To discuss and illustrate the role of ultra-widefield fluorescein angiography (UWFFA) in the diagnosis and management of peripheral retinal vasculitis. DESIGN: Retrospective case series. PARTICIPANTS: Four consecutive patients in whom UWFFA showed far peripheral vasculitis were included. All patients were seen between May 2011 and May 2012 at the Doheny Eye Institute. METHODS: Conventional fluorescein angiogram (FA) images or areas determined by the Early Treatment of Diabetic Retinopathy Study Group protocol for imaging the posterior pole and peripheral retina were superimposed on the UWFFA images. The ability to detect the extent and severity of vasculitis and vascular occlusion using both conventional FA and UWFFA was compared by 2 investigators, and any discrepancies were adjudicated by a third investigator. RESULTS: In none of the cases was the full extent of vasculitis and capillary occlusion visible in the fields normally portrayed by conventional FA. In contrast, capillary nonperfusion and peripheral vasculitis were detectable by UWFFA in all cases. In 2 cases, the posterior extent of vasculitis could have been detected by conventional FA. CONCLUSIONS: Detection and depiction of the extent and severity of peripheral vascular changes are enhanced with UWFFA, aiding in the management of vasculitis in the retinal periphery.