Multimodal imaging in a case of presumed secondary vitreoretinal lymphoma presenting with inner retina and optic nerve head infiltration.

Purpose: To report the findings supported by multimodal imaging in a case of secondary vitreoretinal lymphoma presenting with inner retina and optic nerve head infiltration. Observations: A 64-year-old man with systemic diffuse large B-cell lymphoma presented with reduced visual acuity. Moderate anterior chamber and vitreous cell were present. Fundus exam showed bilateral disc edema and diffuse opaque macular infiltrates with a pseudo cherry-red spot in the left eye. Optical coherence tomography showed inner retinal infiltration and loss of normal architecture. Surgery for tissue biopsy was discussed and declined due to risk. Instead, multimodal imaging and anterior chamber fluid sampling were used as a surrogate for tissue biopsy and helped rule out infectious uveitis and retinal vascular disease. The patient was empirically treated with intravitreal methotrexate with rapid improvement in vision, exam, and quality of life. Conclusions and importance: Multimodal imaging can support a presumed diagnosis of secondary vitreoretinal lymphoma in order to proceed with intravitreal methotrexate treatment, which can result in rapid clinical and visual improvement.

Recovering Safety: A Pilot Study of a Women's Empowerment Group for Survivors of Intimate Partner Violence with Substance Use Disorders.

This pilot study examined the feasibility and satisfaction of the Recovering Safety group, an outpatient empowerment, psychoeducational skills group for women with substance use disorders (SUDs) who have experienced intimate partner violence (IPV). Patient satisfaction, empowerment, and safety were assessed at three time points. Participants (N=8) reported high satisfaction with the group and rated the IPV-informed content, women-only participants, and female therapist as important factors; empowerment increased from pre- to post group. These results support initial feasibility; further study of such treatments is needed to examine efficacy of this group intervention.

Disability-Adjusted Life Years Resulting from Ocular Injury among Deployed Service Members, 2001-2020.

PURPOSE: To quantify the burden of ocular injuries on deployed US service members by calculating disability-adjusted life years (DALYs). DESIGN: Retrospective, observational cohort study. PARTICIPANTS: US service members with ocular injuries sustained in combat zones from January 1, 2001 to May 19, 2020. METHODS: Health states and duration of injuries were identified using data from the Defense and Veterans Eye Injury and Vision Registry. These health states were mapped to disability weights from the Global Burden of Disease (GBD) study. Average duration of injury or illness was calculated until remission or death. For the latter, life expectancy at age of sustaining injury, as identified from US Life Tables from the National Vital Statistics Reports 2020, was used. Using Defense Manpower Data Center reports capturing number of service members deployed per year, incidence rates were calculated for ocular injury and DALYs. MAIN OUTCOME MEASURES: Disability-adjusted life years of ocular injury. RESULTS: Seventeen thousand five hundred fifty-five patients sustained ocular injury that incurred DALYs. In total, these injuries resulted in 11 214 DALYs (average, 0.64 DALYs per included patient and 20.6 DALYs per 10 000 US service members per year). Severe impairment of distance vision (77.9%) and blindness (10.6%) were the primary contributors of DALYs. Although only 9.3% of patients sustained a permanent ocular injury, permanent disability accounted for 99.5% of total DALYs. The average yearly incidence rate of ocular injury was 32.0 cases per 10 000 US service members. Foreign body was the most frequent injury type (2754 occurrences), followed by abrasion (2419 occurrences) and multiple injury types (1429 occurrences). The most DALYs occurred in patients with multiple injury types (2485 DALYs), followed by abrasion (accounting for 725 DALYs) and foreign body (accounting for 461 DALYs). DISCUSSION: We report higher average DALYs per case ratio among US service members compared with the general population studied by the GBD study, highlighting the differences in probabilities of permanent injury between the two studies. Our study provides understanding of the impact of ocular injuries on active-duty service members and lays the groundwork for further research and interventions to mitigate their burden. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Persistent diabetic macular edema: Definition, incidence, biomarkers, and treatment methods.

Intravitreal antivascular endothelial growth factor (anti-VEGF) treatment has drastically improved the visual and anatomical outcomes in patients with diabetic macular edema (DME); however, success is not always guaranteed, and a proportion of these eyes demonstrate persistent DME (pDME) despite intensive treatment. While standardized criteria to define these treatment-resistant eyes have not yet been established, many studies refer to eyes with no clinical response or an unsatisfactory partial response as having pDME. A patient is considered to have pDME if the retinal thickness improves less than 10-25% after 6 months of treatment. A range of treatment options have been recommended for eyes with pDME, including switching anti-VEGF agents, using corticosteroids and/or antioxidant drugs in adjunct with anti-VEGF therapy, and vitrectomy. In addition, multimodal imaging of DME eyes may be advantageous in predicting the responsiveness to treatment; this is beneficial when initiating alternative therapies. We explore the literature on persistent DME regarding its defining criteria, incidence, the baseline biological markers that may be useful in anticipating the response to treatment, and the available treatment options.

Alcohol Treatment Access and Engagement Among Women in the USA: a Targeted Review of the Literature 2012-2022.

Purpose of Review: The purpose of this review is to examine recent literature (2012-2022) on alcohol treatment access and engagement in women in the U.S. and propose future directions for research and clinical practice. Recent Findings: A targeted literature review resulted in 27 studies encompassing screening and brief intervention (SBIRT), treatment utilization, treatment engagement, and barriers to treatment. Recent literature demonstrates overall low rates of screening and brief interventions and treatment utilization in the population with women less likely to be screened and utilize alcohol treatment. The magnitude of these gender differences varies with race/ethnicity. Extensive barriers to care include provider knowledge, structural barriers, and attitudinal barriers and these vary with service setting, gender, and race/ethnicity. Summary: There is an increasing prevalence of alcohol use and Alcohol Use Disorder (AUD) in women with low rates of screening, brief treatment, treatment, and engagement which have resulted from extensive barriers to care. Possible areas of further inquiry include the impact of race/ethnicity on gender differences, improving provider and system level policies to promote SBIRT and treatment engagement and utilization, further developing digital interventions, and implementation research to investigate factors associated with optimizing effectiveness of gender-responsive and culturally tailored interventions that address the unique needs of women.

MULTISCALE CORRELATION OF MICROVASCULAR CHANGES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH RETINAL SENSITIVITY IN DIABETIC RETINOPATHY.

PURPOSE: To assess global, zonal, and local correlations between vessel density changes measured by optical coherence tomography angiography and retinal sensitivity measured by microperimetry across diabetic retinopathy severity. METHODS: Diabetic patients and nondiabetic controls underwent optical coherence tomography angiography imaging and microperimetry testing. Pearson's correlation was used to assess associations between average sensitivity and skeletonized vessel density (SVD) or foveal avascular zone area centrally. Linear mixed effects modeling was used to assess relationships between local SVD measurements and their spatially corresponding retinal sensitivity measurements. RESULTS: Thirty-nine eyes from 39 participants were imaged. In all slabs, there was a statistically significant positive correlation between retinal sensitivities and SVDs on both global and zonal scales. No statistically significant correlation was found between central retinal sensitivities and the foveal avascular zone areas. Assessment of 1,136 spatially paired retinal sensitivity and SVD measurements revealed a statistically significant local relationship; this seemed to be driven by eyes with proliferative diabetic retinopathy that had reduced retinal sensitivities. CONCLUSION: This study supports positive correlations between SVD and retinal sensitivity at global and zonal spatial scales in diabetic eyes. However, our analysis did not find evidence of statistically significant correlations between retinal sensitivity and SVD on a local scale until advanced diabetic retinopathy.

Modeling the impact of COVID-19 on Retina Clinic Performance.

BACKGROUND: COVID-19, a highly contagious respiratory virus, presents unique challenges to ophthalmology practice as a high-volume, office-based specialty. In response to the COVID-19 pandemic, many operational changes were adopted in our ophthalmology clinic to enhance patient and provider safety while maintaining necessary clinical operations. The aim of this study was to evaluate how measures adopted during the pandemic period affected retina clinic performance and patient satisfaction, and to model future clinic flow to predict operational performance under conditions of increasing patient and provider volumes. METHODS: Clinic event timestamps and demographics were extracted from the electronic medical records of in-person retina encounters from March 15 to May 15, 2020 and compared with the same period in 2019 to assess patient flow through the clinical encounter. Patient satisfaction was evaluated by Press Ganey patient experience surveys obtained from randomly selected outpatient encounters. A discrete-events simulation was designed to model the clinic with COVID-era restrictions to assess operational performance under conditions of increasing patient and provider volumes. RESULTS: Retina clinic volume declined by 62 % during the COVID-19 health emergency. Average check-in-to-technician time declined 79 %, total visit length declined by 46 %, and time in the provider phase of care declined 53 %. Patient satisfaction regarding access nearly doubled during the COVID-period compared with the prior year (p < 0.0001), while satisfaction with overall care and safety remained high during both periods. A model incorporating COVID-related changes demonstrated that wait time before rooming reached levels similar to the pre-COVID era by 30 patients-per-provider in a 1-provider model and 25 patients-per-provider in a 2-provider model (p < 0.001). Capacity to maintain distancing between patients was exceeded only in the two 2-provider model above 25 patients-per-provider. CONCLUSIONS: Clinic throughput was optimized in response to the COVID-19 health emergency. Modeling these clinic changes can help plan for eventual volume increases in the setting of limits imposed in the COVID-era.

Macular Vessel Density in Diabetic Retinopathy Patients: How Can We Accurately Measure and What Can It Tell Us?

Diabetic retinopathy is one of the leading causes of blindness worldwide. Optical coherence tomography angiography (OCTA) is a non-invasive technology that provides depth-resolved images of the chorioretinal vasculature and allows for the understanding of the changes in vasculature with diabetic retinopathy. Not only can it provide qualitative information, but OCTA can also provide quantitative information about the vasculature in patients with diabetic retinopathy. Macular vessel density is one of the quantitative metrics that can be obtained from OCTA images. This is a repeatable and non-subjective measurement that can provide valuable insight into the pathophysiology of diabetic retinopathy. In this non-systematic review, the measurement of macular vessel density in diabetic retinopathy and the reasons for its importance in the diagnosis and management of patients with diabetes and varying severities of diabetic retinopathy is discussed.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN SMALL CHOROIDAL MELANOMAS AND CHOROIDAL NEVI.

PURPOSE: To evaluate the use of swept-source optical coherence tomography angiography to detect distinct vascular features in small choroidal melanomas and choroidal nevi. METHODS: Patients with a choroidal nevus or a treatment-naïve choroidal melanoma were imaged with color fundus photography, ultrasound, and swept-source optical coherence tomography angiography (12 × 12 mm). High-risk features including overlying fluid, orange pigment, shaggy photoreceptors, acoustic hollowness, depth >2 mm, and basal diameter >5 mm were assessed. Optical coherence tomography angiography vascular markers included: choroidal vessel visualization, choroidal vessel depth, and choriocapillaris flow signal, assessed qualitatively by comparison with surrounding, unaffected choriocapillaris. RESULTS: Twenty-nine lesions were included in this study, seven flat choroidal nevi, 17 elevated choroidal nevi, and 5 choroidal melanomas. Distinct vascular patterns were noted between flat nevi, elevated nevi, and small choroidal melanomas. Choroidal melanomas displayed two types of vasculature: "nevus-like" vasculature with straight parallel vessels and complex vasculature with vascular loops and crosslinking. Visualized choroidal vessels were significantly deeper in melanomas (110 µm) than elevated (84 µm) or flat nevi (70 µm). In a size-matched subanalysis of 5 elevated choroidal nevi and 5 choroidal melanomas, choroidal melanomas had increased mean choroidal vessel depth (P = 0.015), deepest choroidal vessel visualized (P = 0.034), and presence of a deep choroidal vessel >155 µm (P = 0.048). CONCLUSION: Swept-source optical coherence tomography angiography may detect distinct vascular features in choroidal nevi and small choroidal melanomas.

Retinal Imaging Using a Confocal Scanning Laser Ophthalmoscope-Based High-Magnification Module.

PURPOSE: To evaluate the usefulness of a high-magnification module (HMM) lens to visualize retinal photoreceptors, retinal nerve fiber layer (RNFL), and superficial retinal vasculature in physiologic and pathologic retinal conditions. DESIGN: Observational descriptive study. PARTICIPANTS: Thirty-two participants with normal and pathologic retina examination results. METHODS: Normal and pathologic maculae were imaged in vivo using still and video HMM lens modes, with fixation and contrast adjustments to enhance visualization. The HMM images were classified qualitatively based on structures identified as either good (photoreceptors seen), average (photoreceptor mosaic cannot be visualized clearly, retinal vessels and other retinal changes can be seen), or poor (no identifiable structures). Selected eyes were imaged with fundus photography, OCT, OCT angiography, indocyanine green angiography, and fluorescein angiography for comparison with the pathologic maculae. MAIN OUTCOMES MEASURES: Description of HMM module-obtained macula images. RESULTS: From 32 eyes imaged (16 normal and 16 pathologic retinas), 12 of 16 normal and 11 of 16 pathologic retinas demonstrated at least average image quality, in which retinal vasculature and landmarks could be visualized. The mosaic pattern of hexagonal shapes representing photoreceptors could not be resolved in most pathologic retinas. For the retinas in which the photoreceptor mosaics were visualized (12 of 16 normal and 2 of 16 pathologic retinas), parafoveal mosaic patterns appeared denser with better image quality for all participants compared with foveal photoreceptors. Difficulty in resolving the photoreceptors in the umbo, fovea, and perifovea was encountered, similar to what has been reported with adaptive optics devices. The RNFL was seen as arcuate hyperreflective bundles. Flow was observed in the macular microvasculature. Poorly resolved photoreceptors and scattered hyperreflective foci were correlated with changes in the retinal pigment epithelium in eyes with age-related macular degeneration or central serous chorioretinopathy. Macular striae were seen in eyes with epiretinal membrane. CONCLUSIONS: In most eyes, regardless of whether retinal pathologic features were present, it was challenging to obtain average quality (or better) images. In the few participants with good-quality imaging, the parafoveal photoreceptor mosaic, vascular flow, and various features of pathologic eyes could be visualized.

Can the Onset of Neovascular Age-Related Macular Degeneration Be an Acceptable Endpoint for Prophylactic Clinical Trials?

Many studies over the past 20 years have pursued the goal of preventing or deferring progression from early and intermediate age-related macular degeneration (AMD) to advanced AMD. The onset of neovascular AMD has been used as a primary endpoint in some prophylactic clinical trials because it is easy to assess and relatively well-defined. Nevertheless, the use of this endpoint for assessing progression of AMD lacks validation. The aims of this paper are to review the current practice of clinical trials investigating the prevention of progression of early or intermediate AMD to neovascular AMD, so-called prophylactic trials, as well as identify ongoing efforts to standardize endpoints and select the ideal population for such studies.

Choroidal nonperfusion on optical coherence tomography angiography in a case of unilateral posterior segment ocular sarcoidosis misdiagnosed as MEWDS.

PURPOSE: To report a case of presumed ocular sarcoidosis initially presenting with features of multiple evanescent white dot syndrome (MEWDS) with atypical optical coherence tomography angiography (OCTA) findings. OBSERVATIONS: A 23 year-old woman presented with a unilateral central scotoma, photophobia, and decreased visual acuity after a viral illness. Examination of the right eye revealed multiple round white macular spots and stippled granularity at the fovea. Multimodal imaging with fluorescein angiography (FA), indocyanine green angiography (ICG), fundus autofluorescence (FAF), and optical coherence tomography (OCT) was consistent with a diagnosis of MEWDS. However, OCTA demonstrated choriocapillaris (CC) flow deficits, which is not typical for MEWDS. The clinical course was initially consistent with MEWDS, with spontaneous recovery of symptoms over ensuing months. The patient presented five months later with floaters and a central scotoma. Examination showed panuveitis, and systemic evaluation revealed an elevated angiotensin converting enzyme (ACE) and hilar lymphadenopathy on chest x-ray consistent with presumed sarcoidosis. CONCLUSIONS AND IMPORTANCE: A case of MEWDS atypically demonstrated CC flow deficits on OCTA and subsequently presented as uveitis secondary to presumed sarcoidosis. Atypical features in MEWDS may be a sign of another disorder masquerading early on as MEWDS and ought to prompt further investigation.

The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration.

BACKGROUND: The short-term effects of anti-vascular endothelial growth factor (anti-VEGF) treatment on macular neovascularization (MNV) morphology is well described, but long-term studies on morphologic changes and correlation of such changes to the type of MNV have not been conducted. This study aims to determine if different types of MNVs in neovascular AMD (nAMD) behave differently with anti-VEGF treatment as visualized on optical coherence tomography angiography (OCTA). METHODS: Treatment-naïve nAMD patients were retrospectively screened for baseline and follow-up OCTA imaging 10 or more months after initial treatment. Images were graded for MNV type, area, activity, mature versus immature vessels, vessel density, presence of atrophy, atrophy location and area. Growth rate was calculated as the percent change in lesion area from baseline over the years of follow-up. In addition, the occurrence of complete regression and the percent of lesions that grew, remained stable, and shrunk per type was also evaluated. RESULTS: Forty-three eyes from 43 patients with a mean follow-up of 2 years were evaluated. On structural OCT, 26 lesions were classified as pure type 1 MNVs, 12 MNVs had a type 2 component, and 5 MNVs had a type 3 component. Of these cases, 2 mixed-type MNVs were considered to have completely regressed. There was no significant differences in MNV area and growth rate between type 1 and type 2 lesions, but all cases of type 3 lesions shrunk in the follow-up period. There was no correlation between the number of injections per year and growth rate, endpoint MNV area or endpoint activity status for any MNV type. There was no significant association between the development of atrophy and the number of injections, baseline MNV area, baseline vessel density, or lesion growth rate. CONCLUSIONS: In nAMD, complete regression of an MNV network exposed to anti-VEGF is rare. This work emphasizes the role of anti-VEGF as anti-leakage rather than vascular regression agents in nAMD.

Wide-field optical coherence tomography angiography for the detection of proliferative diabetic retinopathy.

PURPOSE: To compare the ability of wide-field optical coherence tomography angiography (WF-OCTA) to that of ultra-wide field fluorescein angiography (UWF-FA) and ultra-wide-field color fundus photography (UWF-CP) to detect retinal neovascularization (NV) in eyes with proliferative diabetic retinopathy (PDR). METHODS: In this cross-sectional study, naïve patients with active PDR underwent UWF-FA and UWF-CP using the Optos 200Tx and WF-OCTA with 12 × 12 mm fields of five visual fixations using the PLEX Elite 9000. NV was defined on OCTA when the co-registered B-scan with flow overlay of the vitreoretinal interface (VRI) segmentation showed extraretinal proliferation. Three masked readers examined the UWF-FA, UWF-CP, and WF-OCTA independently for the presence of NV. Statistical analysis was performed to compare the diagnostic accuracy of the 3 wide-field imaging modalities using OCT B-scan as the reference standard. RESULTS: In 82 eyes with PDR, neovascularization of the disc (NVD) was detected in 13 eyes by UWF-CP, 35 eyes with UWF-FA, and 37 eyes with OCTA using the VRI slab. Upon review of the 2500 OCT B-scans with superimposed flow overlay of each eye, NVD was confirmed in 37 eyes. The sensitivity and specificity of NVD detection were 35.1% and 97.8%, respectively for UWF-CP; 94.6% and 100%, respectively, for UWF-FA; and 100% and 100% for WF-OCTA. One hundred ninety-six foci of neovascularization elsewhere (NVE) were identified with the OCT B-scan with superimposed flow overlay. UWF-CP analysis was able to detect 62 foci of NVE of the 196 confirmed by B-scan (31.6% detection rate). An additional 11 foci of NVE seen on UWF-CP were not confirmed by B-Scan (15% false positive rate). There were 182 foci of NVE identified by UWF-FA (detection rate 91.3%), while WF-OCTA detected 196 retinal NVEs (detection rate 100%). The rate of false positives for both UWF-FA and WF-OCTA was low (< 2%). CONCLUSION: WF-OCTA can identify NV that is not evident in UWF-CP and represents a faster and safer alternative to UWF-FA for surveillance of PDR with comparable diagnostic accuracy.

Macular and Peripapillary Optical Coherence Tomography Angiography Metrics Predict Progression in Diabetic Retinopathy: A Sub-analysis of TIME-2b Study Data.

PURPOSE: To identify optical coherence tomography angiography (OCTA)-derived vessel metrics of the macula and optic nerve head (ONH) that predict diabetic retinopathy (DR) disease progression. DESIGN: Secondary analysis of clinical trial data. METHODS: This was a sub-analysis of prospectively collected data from 73 subjects that participated in the TIME-2b study (Aerpio Pharmaceuticals), a multicenter clinical trial for patients with moderate-to-severe DR treated with AKB-9778 and followed over a 12-month period. Eligible subjects were tested every 3 months with color fundus photography, spectral-domain OCT, and slit-lamp biomicroscopy. OCTA of the macula and ONH was obtained for a subset of patients enrolled at participating sites. En face, full-depth retinal projections centered at the macula were analyzed for multiple metrics including foveal avascular zone (FAZ) area and perimeter, nonperfusion area, vessel density (VD), and presence of intraretinal microvascular abnormalities (IRMA). VD of the radial peripapillary capillaries was evaluated in 4 quadrants surrounding the optic disc for ONH images. Progression was defined as a ≥2-step increase in DR severity scale score or development of diabetic macular edema. RESULTS: Over a follow-up period of 12 months, 15 of 73 (20.5%) subjects progressed. At pretreatment baseline, larger FAZ area, presence of IRMA, and reduced peripapillary VD in the superior temporal and inferior temporal regions were significantly associated with increased odds of progression. CONCLUSIONS: FAZ area and temporal peripapillary VD are predictors of DR progression. OCTA metrics may improve progression risk assessment in DR when compared to established risk factors alone.

Repeatability and reproducibility of vessel density measurements on optical coherence tomography angiography in diabetic retinopathy.

PURPOSE: Understanding the precision of measurements on and across optical coherence tomography angiography (OCTA) devices is critical for tracking meaningful change in disease. The purpose of this study is to investigate the repeatability and reproducibility of vessel area density and vessel skeleton density measurements from various commercial OCTA devices in diabetic eyes. METHODS: Patients were imaged three consecutive times each on three different OCTA devices. En face OCTA images of the superficial capillary plexus, deep capillary plexus, and full retinal layer were exported for analysis. Vessel area density and vessel skeleton density were calculated. The coefficient of repeatability (CoR) was calculated to assess the repeatability of these measurements, and linear mixed models were utilized to assess the reproducibility of these measurements. RESULTS: Forty-four eyes from 27 diabetic patients were imaged. Normalized CoR values ranged between 3.44 and 6.65% when calculated for vessel area density and between 1.35 and 23.39% when calculated for vessel skeleton density. When stratified by disease severity, the swept-source OCTA device consistently produced the smallest CoR values for vessel area density in the full retinal layer. Vessel area density measurements were repeatable across the two spectral-domain devices in the full retinal layer when all severities were combined, as well as in diabetic patients without retinopathy, mild nonproliferative diabetic retinopathy (NPDR), and moderate NPDR. CONCLUSION: Vessel area density measured in the full retinal layer may be a more precise measure than vessel skeleton density to follow diabetic retinopathy patients both on the same device and across devices.

Test-retest variability of microperimetry in geographic atrophy.

PURPOSE: Microperimetry (MP) allows for measurement of retinal sensitivity at precise locations and is now commonly employed as a clinical trial endpoint. Test-retest reliability is important when evaluating treatment effects in patients with geographic atrophy (GA). This study aimed to determine the test-retest variability of MP in patients with moderate to severe GA using the MAIA MP device. METHODS: In this prospective study, patients with a confirmed diagnosis of foveal-involving GA were enrolled. Participants performed three MP assessments of a selected eye over two visits with the Macular Integrity Assessment (MAIA) 2 instrument (Centervue, Padova, Italy) utilizing a wide 30° grid, consisting of 93 stimuli (Goldmann III) using a 4-2 representation strategy, encompassing the entire area of GA and beyond. Mean retinal sensitivity (MS) was expressed as an average threshold value (dB) for the entire field tested. Coefficients of Repeatability at a 95% level (CoR95) were calculated for Point Wise Sensitivity (PWS). Fixation stability (FS) was assessed by evaluating the area of an elliptical representation encompassing 95% of the cloud of fixation points (CFP) dataset generated by the MAIA MP, known as the bivariate contour ellipse area (BCEA). RESULTS: A total of 8 subjects were enrolled (21 tests), with six subjects completing 3 MP assessments. BCVA in these patients ranged from 20/100 to 20/800. The mean area of GA was 18.7 ± 12.3 mm2. The average time to complete one MP assessment was 13 min 9 s and mean BCEA@95% was 38.5 ± 19.3°2. The MS was 14.3 ± 4.5 dB. No significant increase in MS was noted between testing pairs 1&2 and 2&3. The preferred retinal locus was maintained in the same quadrant on successive tests. The mean CoR95 for PWS were similar for testing pairs 1&2 (± 3.50 dB) and 2&3 (± 3.40). CONCLUSION: Microperimetry using a wide grid can be reliably performed in a reasonable amount of time in patients with moderate and severe vision loss secondary to GA. There was no learning effect seen between sequential assessments when analyzing MS or PWS. A change of approximately 4 dB in PWS provides a threshold for considering a true change in this patient cohort.

Topographic analysis of macular choriocapillaris flow deficits in diabetic retinopathy using swept-source optical coherence tomography angiography.

BACKGROUND: The purpose of this study was to investigate the association between diabetic retinopathy (DR) severity and macular choriocapillaris (CC) flow deficit percentage (FD %) in different macular regions using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Diabetic patients with SS-OCTA images were graded by severity and retrospectively assessed. CC FD % was calculated in four different regions of the OCTA image: inner, middle, outer, and full-field region. The generalized estimating equations (GEE) approach for clustered eye data was used to determine effect size and significance of age and disease severity on FD % for each region. RESULTS: 160 eyes from 90 total diabetic patients met inclusion criteria. Out of 90 patients, 33 had no DR, 17 had mild nonproliferative DR (NPDR), 8 had moderate NPDR, 10 had severe NPDR and 22 had proliferative DR. Age and DR severity had a significant positive association with FD % for each region studied with a greater effect in the two centermost regions. The increase in flow deficit percentage per year of age by region was: inner 0.12 (p < 0.001), middle 0.09 (p < 0.001), outer 0.05 (p < 0.001, full-field 0.06 (p < 0.001). The increase in flow deficit percentage per increase in diabetic retinopathy severity stage by region was: inner 0.65 (p < 0.0087), middle 0.56 (p < 0.0012), outer 0.33 (p < 0.045), full-field 0.36 (p < 0.018). CONCLUSIONS: Topographic analysis of the CC FD % in diabetic eyes suggests that CC flow impairment corresponds to DR severity, with all studied regions of the CC significantly affected. There was greater regional impairment due to age and disease severity in the inner and middle regions.

Pain and Problem Behavior in Cats and Dogs.

We argue that there is currently an under-reporting of the ways in which pain can be associated with problem behavior, which is seriously limiting the recognition of this welfare problem. A review of the caseloads of 100 recent dog cases of several authors indicates that a conservative estimate of around a third of referred cases involve some form of painful condition, and in some instances, the figure may be nearly 80%. The relationship is often complex but always logical. Musculoskeletal but also painful gastro-intestinal and dermatological conditions are commonly recognized as significant to the animal's problem behavior. The potential importance of clinical abnormalities such as an unusual gait or unexplained behavioral signs should not be dismissed by clinicians in general practice, even when they are common within a given breed. In general, it is argued that clinicians should err on the side of caution when there is a suspicion that a patient could be in pain by carefully evaluating the patient's response to trial analgesia, even if a specific physical lesion has not been identified.

Monocyte infiltration rather than microglia proliferation dominates the early immune response to rapid photoreceptor degeneration.

BACKGROUND: Activation of resident microglia accompanies every known form of neurodegeneration, but the involvement of peripheral monocytes that extravasate and rapidly transform into microglia-like macrophages within the central nervous system during degeneration is far less clear. METHODS: Using a combination of in vivo ocular imaging, flow cytometry, and immunohistochemistry, we investigated the response of infiltrating cells in a light-inducible mouse model of photoreceptor degeneration. RESULTS: Within 24 h, resident microglia became activated and began migrating to the site of degeneration. Retinal expression of CCL2 increased just prior to a transient period of CCR2+ cell extravasation from the retinal vasculature. Proliferation of microglia and monocytes occurred concurrently; however, there was no indication of proliferation in either population until 72-96 h after neurodegeneration began. Eliminating CCL2-CCR2 signaling blocked monocyte recruitment, but did not alter the extent of retinal degeneration. CONCLUSIONS: These results demonstrate that the immune response to photoreceptor degeneration includes both resident microglia and monocytes, even at very early times. Surprisingly, preventing monocyte infiltration did not block neurodegeneration, suggesting that in this model, degeneration is limited by cell clearance from other phagocytes or by the timing of intrinsic cell death programs. These results show monocyte involvement is not limited to disease states that overwhelm or deplete the resident microglial population and that interventions focused on modulating the peripheral immune system are not universally beneficial for staving off degeneration.