E
E J-Y, Mihailovic A, Schrack JA, Garzon C, Li T, Friedman DS, West SK, Gitlin LN, Ramulu PY.
Longitudinal changes in daily patterns of objectively measured physical activity after falls in older adults with varying degrees of glaucoma. EClinicalMedicine 2021;40:101097.
AbstractBackground: Visually impaired older adults have a greater risk of falling, making them particularly susceptible to fall-related health consequences and restricted physical activity. Unclear however, is the relationship between having falls and longitudinal changes in daily patterns of objectively measured physical activity in older adults with visual impairments. Methods: We created a three-year prospective cohort study (Falls in Glaucoma Study) of older adults with primary or suspected glaucoma at the Johns Hopkins Wilmer Eye Institute from 2013 to 2015. Cumulative incidence of falls was determined through self-reported fall calendars over 12 months. Participants were then classified into one of three groups: multiple fallers (≥2 falls), single fallers (1 fall), and non-fallers (0). Daily physical activity was measured over 1 week using a waist-bound accelerometer during baseline and three-year follow-ups. Activity fragmentation was defined as the reciprocal of the mean activity bout length, with higher fragmentation reflecting shorter, more fractured bouts of continuous activity. Multivariate linear mixed-effects models were used to assess three-year longitudinal changes in: 1) activity fragmentation, and 2) accumulation of activity across six three-hour intervals from 5 AM to 11 PM. Findings: In adjusted models accounting for visual field damage and other factors, multiple fallers demonstrated greater annual declines (per year) in daily active bouts (-1.79 bouts/day, 95% confidence interval [CI]: -3.35, -0.22), daily active minutes (-17.15 min/day, 95% CI: -26.35, -7.94), and increased fragmentation (1%, 95% CI: 0, 2%) over the three-year follow-up period as compared to non-fallers; no such changes were seen when comparing single fallers and non-fallers. In time-of-day analyses, multiple fallers experienced greater annual declines in average hourly steps over all periods of the day, though the rate of decline was only significant between 5 PM and 8 PM (-27.07 steps/hour, 95% CI: -51.15, -2.99) compared to non-fallers. Interpretation: In an older population with visual impairment, multiple falls over 12 months were associated with more transient and fragmented activity over a subsequent three-year period, and activity declines during evening hours, compared to non-fallers. These findings suggest that multiple fallers with visual impairment may be at high risk for a decline in physical capacity and endurance, warranting clinical interventions. Funding: The research was supported in part by National Institutes of Health Grant EY022976.
E J-Y, Schrack JA, Mihailovic A, Wanigatunga AA, West SK, Friedman DS, Gitlin LN, Li T, Ramulu PY.
Patterns of Daily Physical Activity across the Spectrum of Visual Field Damage in Glaucoma Patients. Ophthalmology 2021;128(1):70-77.
AbstractPURPOSE: To define and quantify patterns of objectively measured daily physical activity by level of visual field (VF) damage in glaucoma patients including: (1) activity fragmentation, a metric of health and physiologic decline, and (2) diurnal patterns of activity, a measure of rest and activity rhythms. DESIGN: Prospective cohort study. PARTICIPANTS: Older adults diagnosed with glaucoma or suspected glaucoma. METHODS: Degree of VF damage was defined by the average VF sensitivity within the integrated VF (IVF). Each participant wore a hip accelerometer for 1 week to measure daily minute-by-minute activity for 7 consecutive days. Activity fragmentation was calculated as the reciprocal of the average activity bout duration in minutes, with higher fragmentation indicating more transient, rather than sustained, activity. Multivariate linear regression was used to test for cross-sectional associations between VF damage and activity fragmentation. Multivariate linear mixed-effects models were used to assess the associations between VF damage and accumulation of activity across 6 3-hour intervals from 5 am to 11 pm. MAIN OUTCOME MEASURES: Activity fragmentation and amount of activity (steps) over the course of the day. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with 16.3 fewer active minutes/day (P < 0.05) and 2% higher activity fragmentation (P < 0.05), but not with the number of active bouts per day (P = 0.30). In time-of-day analyses, lower IVF sensitivity was associated with fewer steps over the 11 am to 2 pm, 2 pm to 5 pm, and 5 pm to 8 pm periods (106.6, 93.1, and 89.2 fewer steps, respectively; P < 0.05 for all), but not over other periods. The activity midpoint (the time at which half of the daily activity is completed) did not vary across level of VF damage. CONCLUSIONS: At worse levels of VF damage, glaucoma patients demonstrate shorter, more fragmented bouts of physical activity throughout the day and lower activity levels during typical waking hours, reflecting low physiologic functioning. Further work is needed to establish the temporality of this association and whether glaucoma patients with such activity patterns are at a greater risk of adverse health outcomes associated with activity fragmentation.
E J-Y, Mihailovic A, Schrack JA, Li T, Friedman DS, West SK, Gitlin LN, Ramulu PY.
Characterizing Longitudinal Changes in Physical Activity and Fear of Falling after Falls in Glaucoma. J Am Geriatr Soc 2021;69(5):1249-1256.
AbstractBACKGROUND: Older adults with visual impairments experience a higher risk of falling, and are more vulnerable to adverse health consequences associated with falls than those with normal vision. This study characterizes longitudinal changes in objectively measured physical activity and fear of falling (FoF) occurring after various types of falls in visually impaired older adults. DESIGN: Prospective cohort study. SETTING: Hospital-based enrollment. PARTICIPANTS: People with glaucoma or suspected glaucoma. MEASUREMENTS: Falls were defined as unintentionally coming to rest on the ground or a lower level, and injurious falls were determined though follow-up calls. Study participants were categorized into three groups-fallers with injurious consequences, fallers without injurious consequences, and non-fallers based on fall status in the first year. Physical activity was assessed by waist-bound accelerometer. FoF was evaluated by questionnaire, with Rasch modeling generating FoF scores where higher scores reflected worse FoF. The 3-year longitudinal changes of physical activity and FoF were modeled using mixed-effects models. RESULTS: In linear models fully adjusted for visual field damage and other covariates, physical activity among injurious fallers showed greater annual (per year) declines in daily steps (-425 steps/d, 95% confidence interval (CI) = -793, -57), daily active minutes (-13 min/d, 95% CI = -21, -6), and daily moderate and vigorous physical activity (MVPA) minutes (-3 MVPA minutes/d, 95% CI = -5, 0) over the 3-year period as compared to non-fallers; however, physical activity did not significantly decline among non-injurious fallers. No longitudinal increases in FoF scores were observed in injurious or non-injurious fallers when compared to non-fallers. CONCLUSION: Among visually impaired older adults, injurious falls identified prospectively over 12 months contributed to a significant decline in physical activity over a 3-year period, while minimal changes were observed in FoF.
E J-Y, Mihailovic A, Garzon C, Schrack JA, Li T, West SK, Friedman DS, Gitlin LN, Ramulu PY.
Importance and severity dependence of physical activity by GPS-tracked location in glaucoma patients: GPS-tracked physical activity in glaucoma. Am J Ophthalmol 2021;
AbstractPURPOSE: To quantify the association of visual field (VF) damage on physical activity away-from-home, per away-from-home excursion, and at home. DESIGN: Prospective cohort study. METHODS: Among 229 participants with glaucoma or suspected glaucoma, severity of VF damage was defined as average sensitivity within the integrated VF (IVF). Participants wore accelerometers and GPS trackers for seven days to measure physical activity and characterize activity location. Multivariable negative binomial regressions were used to test whether away-from-home activity per day, physical activity per away-from-home excursion, and at home activity per day varied by severity of VF damage. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with a lower amount of away-from-home activities per day [18% less Moderate & Vigorous Physical Activity (MVPA) minutes/day, 95% CI, 0.69 to 0.97], and physical activities per away-from-home excursion (20% less MVPA minutes/excursion, 95% CI, 0.65, 0.98). Similar findings were noted for other away-from-home activity measures (including active minutes/steps per day, or active minutes/steps per excursion). However, worse IVF sensitivity was not associated with measures of at home activities (MVPA minutes/day, active minutes/day, and steps/day), time spent at or away from home, or excursions/week (p>0.1 for all). CONCLUSIONS: Restriction of physical activity in more severe glaucoma patients results mostly from activity restriction outside home environment. These findings highlight the importance of maintaining a safe home environment (where activity is less restricted) and increasing confidence to perform activity, particular high intensity activity, when leaving the home amongst patients with glaucoma.
E J-Y, Mihailovic A, Garzon C, Schrack JA, Li T, West SK, Gitlin LN, Friedman DS, Ramulu PY.
Association Between Visual Field Damage and Gait Dysfunction in Patients With Glaucoma. JAMA Ophthalmol 2021;139(10):1053-1060.
AbstractImportance: Gait dysfunction is common in older people with visual impairment and is a major cause of falls. Objective: To compare 3-year longitudinal changes in gait measures across the spectrum of baseline visual field (VF) damage in glaucoma. Design, Setting, and Participants: A post hoc analysis was designed on September 1, 2018, following a prospective cohort study, which enrolled older adults with glaucoma or suspected glaucoma from September 2013 to March 2015 and followed up for up to 3 years. Baseline VF damage was defined by integrated VF (IVF) sensitivity and categorized as normal/mild (IVF >28 dB), moderate (IVF, 23-28 dB), and severe (IVF, <23 dB). Each participant walked on an electronic walkway back and forth twice at normal pace each study year. Linear mixed-effects models evaluated longitudinal change in gait outcomes (1) stratified within each VF severity category and (2) across the range of IVF sensitivity. Analysis took place from October 2019 to October 2020. Main Outcomes and Measures: Three-year changes in 7 gait assessments under usual-pace walking, including base support and its coefficient of variation, stride length and its coefficient of variation, stride velocity and its coefficient of variation, and cadence. Results: Of 241 participants, the mean (SD) age was 70.8 (7.7) years, 116 (48.2%) were women, and 70 (29.0%) were African American. When comparing longitudinal gait changes over 3 years across the spectrum of IVF sensitivity, each 5-unit (dB) decrement was associated with more rapid declines in stride velocity (-0.05 z score unit/y; 95% CI, -0.09 to -0.01; P = .01) and cadence (-0.07 z score unit/y; 95% CI, -0.10 to -0.03; P < .001). When evaluating gait changes within each glaucoma severity group, shorter stride length was associated with persons with normal/mild (-0.06 z score unit/y; 95% CI, -0.10 to -0.03; P = .001), moderate (-0.08 z score unit/y; 95% CI, -0.12 to -0.04; P < .001), and severe VF damage (-0.16 z score unit/y; 95% CI, -0.24 to -0.07; P < .001), while stride velocity (-0.18 z score unit; 95% CI, -0.28 to -0.07; P = .002) and slower cadence (-0.15 z score unit; 95% CI, -0.25 to -0.04; P = .006) were associated with those with severe VF damage. Conclusions and Relevance: At worse levels of baseline VF damage, patients with glaucoma in this study demonstrated an exacerbated decline in walking speeds (ie, stride velocity and cadence), indicating that mobility speeds decrease faster over time in older adults with glaucoma.
E J-Y, Mihailovic A, Kuo P-L, West SK, Friedman DS, Gitlin LN, Li T, Schrack JA, Ramulu PY.
Characterizing the Impact of Fear of Falling on Activity and Falls in Older Adults with Glaucoma. J Am Geriatr Soc 2020;68(8):1847-1851.
AbstractOBJECTIVE: Fear of falling (FoF) may alter mobility in older adults, especially among those with visual impairment. Using a longitudinal prospective cohort of older glaucoma patients, we investigated whether and how FoF is associated with future falls and physical activity. DESIGN: Prospective observational cohort study. SETTING: Hospital-based single-center recruitment. PARTICIPANTS: Individuals with glaucoma or suspected glaucoma. MEASUREMENTS: FoF was measured annually over a 3-year period using the University of Illinois at Chicago FoF Questionnaire, with lower Rasch-analyzed FoF scores (in logit units) indicating less fear. Participants recorded falls prospectively over the 3-year period using monthly mail-in calendars. Daily steps were collected annually over 7 days using an accelerometer. Visual field (VF) sensitivity was derived by combining sensitivities from monocular VF results. Participants completed questionnaires to determine other demographic/health characteristics. Multivariate random effects models evaluated within-participant changes in fall rates and physical activity across study years. RESULTS: At lower FoF levels (FoF≤0), each one-unit worsening in FoF score across study years was associated with 2.73 times higher odds of reporting at least one fall in the next year (95% confidence interval [CI] = 1.55-4.81) but was not associated with average daily steps (P = .44). Similar results were seen when fall rates were normalized by number of steps taken (P = .97). At higher FoF levels (FoF > 0), inter-year changes in FoF scores were not significantly associated with reporting a fall in the following year (P = .78) but were associated with 407 fewer average daily steps per one-unit change in FoF (95% CI = -743 to -71). CONCLUSION: FoF is an important psychological factor associated with mobility in glaucoma patients, although specific aspects of mobility (fall rates vs activity levels) affected vary by the degree of FoF. Our findings suggest that customizing behavioral interventions for older adults based on their levels of FoF may be an important strategy for fall prevention and activity promotion. J Am Geriatr Soc 68:1847-1851, 2020.
Ebrahimiadib N, Hernandez M, Modjtahedi BS, Roohipoor RC, Foster SC.
Atopy in Patients With Ocular Cicatricial Pemphigoid. Cornea 2018;37(4):436-441.
AbstractPURPOSE: To evaluate the presence of atopy in patients with ocular cicatricial pemphigoid (OCP).
METHOD: Patient encounters between August 2005 and November 2016 at the Massachusetts Eye Research and Surgery Institute (MERSI) were searched to identify those with biopsy-proven OCP who had concurrent evidence of atopy.
RESULTS: There were 230 patients with biopsy-proven OCP. Thirty-three of them were found to have clinical symptoms of atopy (asthma, hay fever, and eczema) and of these, 23 had evidence of atopy in their conjunctival biopsy specimens. All patients were administered immunomodulatory therapy for treatment of their OCP with 20 patients requiring additional antiallergy treatment to control residual atopic ocular symptoms. Among patients who used antiallergy medications, 80% showed improvement in residual symptoms. Rituximab and/or intravenous immunoglobulin is a preferred OCP medication for patients with OCP with some evidence of atopy.
CONCLUSIONS: Clinicians should consider the coexistence of atopy in patients with OCP, especially in those with persistent symptoms after initiation of immunomodulatory therapy.
Ebrahimiadib N, Maleki A, Fadakar K, Manhapra A, Ghassemi F, Foster SC.
Vascular abnormalities in uveitis. Surv Ophthalmol 2021;66(4):653-667.
AbstractInflammation can involve several ocular structures, including the sclera, retina, and uvea, and cause vascular changes in these tissues. Although retinal vasculitis is the most common finding associated with uveitis involving the posterior segment, other vascular abnormalities may be seen in the retina. These include capillary nonperfusion and ischemia, vascular occlusions, preretinal neovascularization, microaneurysms and macroaneurysms, and telangiectasia. Moreover, vasoproliferative tumors and subsequent coat-like response can develop secondary to uveitis. Fluorescein angiography is ideal for the investigation of retinal vascular leakage and neovascularization, while optical coherence tomography angiography can provide depth resolved images from the superficial and deep capillary plexus and can demonstrate vascular remodeling. Choroidal vascular abnormalities primarily develop in the choriocapillaris or in the choroidal stroma and can appear as flow void in optical coherence tomography angiography and filling defect and vascular leakage in indocyanine green angiography. Extensive choriocapillaris nonperfusion in the presence of choroidal inflammation can increase the risk of choroidal neovascular membrane development. Iris vascular changes may manifest as dilation of vessels in stroma due to inflammation or rubeosis that is usually from ischemia in retinal periphery secondary to chronic inflammation. More severe forms of scleral inflammation, such as necrotizing scleritis, are associated with vascular occlusion in the deep episcleral plexus, which can lead to necrosis of sclera layer and uveal exposure.
Ebrahimiadib N, Modjtahedi BS, Davoudi S, Foster SC.
Treatment of Serpiginous Choroiditis with Chlorambucil: A Report of 17 Patients. Ocul Immunol Inflamm 2016;:1-11.
AbstractPURPOSE: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis. METHODS: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3.0-4.5 × 10(9) cells/L. The goal of therapy was to maintain this value for at least 6-9 months. Adverse effects, recurrence, rate of new choroidal neovascularization (CNVM), and visual acuity before and after treatment were recorded. RESULTS: The mean age of the 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil was 46 years, and six patients (35%) were male. The mean duration of treatment for chlorambucil was 8.4 months. None of them developed cancer or persistent side-effects, with a mean follow-up of 53 months. Of the patients, 12 (71%) achieved an average of 45 (5-120) months drug-free remission in their last follow-up. Visual acuity of 33 treated eyes remained within two lines of Snellen acuity in 27 eyes (82%), improved in one eye (3%), and deteriorated in five eyes (15%). Leukopenia was the most common side-effect, which was reversible in all cases. CONCLUSIONS: Chlorambucil in a relatively short duration of time, with an escalating dose guided by weekly WBC was well tolerated, as well as effective in preventing recurrence and maintaining vision in patients with serpiginous choroiditis.
Ebrahimiadib N, Modjtahedi BS, Roohipoor R, Anesi SD, Foster SC.
Successful Treatment Strategies in Granulomatosis With Polyangiitis-Associated Peripheral Ulcerative Keratitis. Cornea 2016;35(11):1459-1465.
AbstractPURPOSE: Management of granulomatosis with polyangiitis (GPA)-associated peripheral ulcerative keratitis (PUK) is challenging and lacks definite guidelines. We aimed to summarize our treatment and outcome experience with patients with GPA-PUK. METHODS: The Massachusetts Eye Research and Surgery Institution patient database was searched from 2005 to 2015 to identify patients with diagnosis of PUK who suffered from GPA. Individual patient histories were examined, and treatment strategies and outcomes were summarized. RESULTS: There were 16 patients who started treatment with a mean duration follow-up of 64 months (range: 12-110 mo). Rituximab and cyclophosphamide, either alone or in combination with other agents, were the most successful agents in controlling inflammation. Rituximab was administered in 11 patients with remission being achieved in all. Cyclophosphamide successfully controlled inflammation in 50% (5/10). Two of the patients (2/5, 40%) who had achieved initial control on cyclophosphamide had flares of their PUK. Two of 11 (18%) patients on rituximab had flares of scleritis and orbital inflammation but not PUK. Two patients, one in each treatment group, stopped treatment after achieving remission after 6 months of therapy but suffered disease recurrence within 2 months of treatment cessation. CONCLUSIONS: Rituximab achieved a high rate of disease control in PUK patients with GPA and is the preferred agent in halting disease progression.
Ebrahimiadib N, Roohipour R, Karkhaneh R, Farahani A, Riazi Esfahani M, Khodabande A, Zarei M, Taheri A, Imani Fouladi M, Yaseri M, Modjtahedi BS.
Internet-based versus Conventional Referral System for Retinopathy of Prematurity Screening in Iran. Ophthalmic Epidemiol 2016;23(5):292-7.
AbstractPURPOSE: To compare the efficacy of an internet-based versus traditional referral system for retinopathy of prematurity (ROP) screening in Iran. METHODS: Two referral screening systems were compared in this prospective observational study. Group A (internet-based) comprised premature babies who were registered into an online system for screening. Their appointments were scheduled automatically based on standardized criteria. Group B (conventional) comprised premature babies whose referrals were based on oral or written recommendations. Babies were referred based on standard criteria (gestational age, GA, <37 weeks or birth weight < 3000 g). RESULTS: A total of 2115 neonates were screened between October 2011 and October 2012. From these 1896 met the inclusion criteria (group A n = 856, group B n = 1040). Time of first examination for neonates with GA≤27 weeks was 30.07± 2.72 weeks postmenstrual age in group A and 38.52± 7.03 weeks in group B (p = 0.049), and for neonates with GA>27 weeks was 4.86 ±1.77 and 8.16 ±4.93 weeks after birth in groups A and B, respectively (p < 0.001). All registered babies in group A attended their first screening exam. One case (0.1%) of advanced ROP developed in group A (in a patient with poor follow-up compliance), whereas advanced stages of ROP were seen in 26 cases (2.5%) in group B (p < 0.001). CONCLUSION: An internet-based registration system for ROP screening resulted in fewer cases of delayed first examination and resulted in fewer babies with advanced ROP.
Ebrahimiadib N, Abusamra K, Domina AM, Stiles ER, Ewer R, Bocian CP, Foster SC.
A Novel NOD2-associated Mutation and Variant Blau Syndrome: Phenotype and Molecular Analysis. Ocul Immunol Inflamm 2016;:1-8.
AbstractPURPOSE: To describe the clinical and molecular implications of a novel mutation in the NOD2/CARD15 gene on a family and its seven affected members. METHODS: We reviewed the clinical presentations of family members who came to our center for refractory uveitis. Genetic testing and molecular testing was performed. RESULTS: All affected members had adult onset recurrent non-granulomatous panuveitis. The inheritance pattern suggested an autosomal dominant disease and genetic analysis identified a novel mutation in the NOD2 gene that converted amino acid 600 from glutamate to alanine (E600A). Transfection of the E600A NOD2 into human embryonic kidney-293 (HEK293) cells revealed constitutive activation and a reduced ability to respond to the NOD2 ligand, muramyl dipeptide (MDP) as compared with wild-type NOD2. CONCLUSIONS: The E600A mutation in the NOD2 gene may confer a higher penetrance of uveitis but a later onset of milder forms of non-ocular involvement.
Ebrahimiadib N, Ma L, Modjtahedi BS, Davoudi S, Rahmani S, Syeda S, Stephenson A, Foster CS.
Atypical Perinuclear Anti-Neutrophil Cytoplasmic Antibodies in Ocular Inflammatory Diseases. Ocul Immunol Inflamm 2018;:1-5.
AbstractPURPOSE: To characterize the clinical features of patients with ocular inflammatory diseases (OID) who tested positive for atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). METHODS: Retrospective case series of patients with OID seen at the Massachusetts Eye Research and Surgery Institute (MERSI) from April 2014 to April 2016. RESULTS: 813 patients were tested for ANCA with 34 patients (4%) being positive for atypical P-ANCA. Among those with positive atypical P-ANCA, the most frequent diagnoses were anterior uveitis in 62% (n = 21) followed by scleritis in 20% (n = 7). Only one patient had an episode of recurrent disease flare-up. All but one patient, who had concomitant C-ANCA seropositivity and granulomatosis with polyangiitis, had a favorable disease course with controlled inflammation using topical and/or systemic immunomodulatory therapy. CONCLUSION: In contrast to typical C-ANCA and P-ANCA, atypical P-ANCA seropositivity was not associated with severe vasculitis or poor prognosis in patients with the OID.
Ebrahimiadib N, Fadakar K, Riazi-Esfahani H, Zarei M, Maleki A, Bojabadi L, Ahmadi A, Look-Why S, Foster CS.
COVID-19 and Immunosuppressive Therapy in Ocular Inflammatory Disease, a Telemedicine Survey. Ocul Immunol Inflamm 2021;:1-7.
AbstractPurpose: Determine the risk of immunomodulatory therapy (IMT) for COVID-19 infection morbidity.Method: A telemedicine survey on patients of a referral uveitis clinic was performed. Signs of infection, habits, and hospitalizations during the 7 months of the COVID-19 pandemic prior to the study date were recorded. Suggestive findings in chest CT scan and/or positive RT-PCR were considered as confirmed COVID-19 infection while those with only suggestive symptoms were considered as suspected cases. Risk factors including sanitary measures and IMT were compared between patients with confirmed cases and patients without infection.Result: 694 patients were included. Eight patients were identified as confirmed cases and 22 patients as suspected cases of COVID-19 infection. Close contact with infected persons was the only significant risk factor for contracting COVID-19.Conclusion: Using IMT did not affect hospitalization and/or ICU admission and can thus be continued during the pandemic, provided that instructions for preventive measures are followed.
