Search

Purpose of Review: This review aims to enhance understanding of juvenile Sjögren's disease (jSjD) by exploring diagnostic criteria, ocular clinical features, ancillary ophthalmic testing, and management strategies specific to this rare pediatric condition., Recent Findings: Unlike adults, children with jSjD often present with recurrent parotitis and extra-glandular symptoms before developing sicca symptoms. Adult SjD classification criteria do not consider pediatric-specific symptoms and physiological differences. Underutilization of diagnostic tests such as the ocular staining score (OSS) and Schirmer I may result in an incomplete understanding of the prevalence of keratoconjunctivitis sicca in jSjD., Summary: Timely referral to an ophthalmologist can address perceived feasibility issues with respect to ocular features in jSjD. Management of keratoconjunctivitis sicca in jSjD includes improving ocular surface lubrication and decreasing inflammation. Recognition of pediatric-specific clinical features and development of universally accepted jSjD classification criteria will allow for better identification of potential participants for future jSjD studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Small-fiber neuropathy (SFN) is known to be associated with Sjögren disease (SjD), and in vivo corneal confocal microscopy can identify features compatible with SFN. Here, we performed a descriptive study to identify features of SFN of the corneal subbasal nerve plexus using in vivo confocal microscopy., Methods: We recruited 10 participants from the Sjögren's International Collaborative Clinical Alliance (SICCA), 1 new participant (in an effort to expand the SICCA cohort), and 22 healthy controls. All participants underwent slit-lamp examination and in vivo confocal microscopy of the central corneal subbasal nerve plexus centered about the central whorl to create a 30-image montage. Each image was analyzed with automated software (ACCmetrics, Manchester, United Kingdom) to produce 7 nerve metrics. We performed t-tests and age-adjusted regressions to make comparisons of nerve metrics between participants with SjD and healthy controls., Results: Most nerve metrics were significantly lower in participants with SjD compared with healthy controls. The mean corneal nerve fiber density was found to be 3.5 mm/mm 2 in participants with SjD compared with 10.6 mm/mm 2 in healthy controls (95% confidence interval, -8.4 to -0.93; P = 0.02). Within the 11 participants with SjD, 22 eyes were analyzed on confocal microscopy, and 16 of those eyes (from 9 individuals) did not have an identifiable central whorl. Within the 22 healthy controls, 22 eyes (right eye alone) were analyzed on confocal microscopy, and 21 of those eyes had an identifiable central whorl., Conclusions: SjD exhibits lower corneal nerve metrics compared with healthy controls. These findings suggest that features compatible with SFN can distinguish SjD from healthy controls and may serve as a potential novel biomarker in identifying SjD., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: In the absence of a gold-standard diagnostic test for different subtypes of dry eye disease (DED), we aimed to identify latent subtypes of DED within a well-characterized cohort., Design: This is a cross-sectional study of participants enrolled in the Sjögren International Collaborative Clinical Alliance (SICCA)., Methods: A latent class analysis was applied to different dry eye-related signs/tests and symptoms of ocular pain (particularly those that aligned with corneal neuropathic pain) giving relative specificities and sensitivities of each diagnostic test or symptom in the SICCA population., Results: Four subtypes of DED were identified with putative designations including normal, asymptomatic dry eye, symptomatic dry eye, and corneal neuropathic pain., Conclusions: More specific classification criteria are needed for DED. Latent class analysis applied to the signs and symptoms captured in the SICCA cohort may allow for the development and refinement of classification criteria for specific subtypes of dry eye., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Sjögren's syndrome (SS) is frequently undetected or misdiagnosed as other rheumatologic diseases. We aimed to develop an SS screening questionnaire for the rheumatology practice., Methods: We developed the Sjögren's Syndrome Screening Questionnaire (SSSQ) via secondary analysis of data from 974 participants referred by rheumatologists to the Sjögren's International Collaborative Clinical Alliance (SICCA) study. Participants answered 88 questions regarding symptoms, medical history, and demographics. They underwent ocular, dental, and serologic tests and were classified as SS or non-SS using the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria. We conducted univariate and multivariate logistic regression to identify questions most discriminative of SS, from which we derived an individual's likelihood of SS ("SSSQ score")., Results: Five questions were significantly discriminative of SS in the multivariate analysis (p < 0.05): (1) Can you eat a cracker without drinking a fluid/liquid? (no: odds ratio [OR], 1.39; 95% confidence interval [CI], 1.06-1.82]); (2) How would you describe your dental and oral health in general? (fair/poor: OR, 1.68; 95% CI, 1.04-2.75); (3) During the last week, have you experienced tearing? (none of the time: OR, 2.26; 95% CI, 1.23-4.34); (4) Are you able to produce tears? (no: OR, 1.62; 95% CI, 1.12-2.37); and (5) Do you currently smoke cigarettes? (no: OR, 2.83; 95% CI, 1.69-4.91). SSSQ score ≥7 (possible range, 0-11) distinguishes SS from non-SS patients with 64% sensitivity and 58% specificity (area under receiver operating characteristic curve, 0.65)., Conclusions: The SSSQ is a simple 5-item questionnaire designed to screen for SS in clinical practice, with a potential impact to reduce delays in diagnosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report the findings of a comprehensive eye examination from an individual with congenital insensitivity to pain because of loss-of-function mutations in the SCN9A gene., Methods: Ophthalmologic examination and confocal microscopy were performed on a patient with congenital insensitivity to pain., Results: A 39-year-old man with compound heterozygous mutations in the SCN9A gene underwent examination. Cochet-Bonnet esthesiometry readings averaged 38 mm (SD 8 mm) in the right eye and 55 mm (SD 7 mm) in the left eye. Other corneal findings included mild conjunctival lissamine green staining, nonvisually significant corneal scars, mild anterior basement membrane dystrophy, and a tear breakup time of 3 seconds in each eye. In vivo confocal microscopy of the corneal subbasal nerve plexus revealed relatively normal corneal nerve morphology, but a reduction in corneal nerve fiber density., Conclusions: An individual with loss-of-function mutations in SCN9A had reduced corneal nerve fiber density but normal corneal mechanoreception., Competing Interests: A. Delwig is an employee of SiteOne Therapeutics. S. G. Waxman is a consultant to SiteOne. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Spica casting (Spica) remains the widely accepted treatment of closed femoral shaft fractures in young children aged 6 months to 5 years. In some centers, there has been a recent trend towards surgical fixation of these fractures with flexible intramedullary nails (FINs). Despite numerous studies evaluating both Spica and FIN treatment of femoral shaft fractures, there remains a paucity of data regarding patient burden during the intraoperative period. The purpose of this study was to compare the intraoperative burden, defined as anesthetic exposure, fluoroscopic duration, and radiation load, between Spica and FIN treatment of femoral shaft fractures in young children., Methods: A retrospective chart review was conducted for pediatric femoral shaft fractures presenting to a tertiary pediatric referral hospital from 2012 to 2017. Comparison groups included pediatric femur fractures treated with Spica and those treated with FIN. Outcomes included anesthetic exposure, fluoroscopy duration, and radiation exposure. In addition, length of stay, clinic visits, and complications were recorded., Results: Of 449 consecutive pediatric femur fractures treated at our center, 143 patients ages 2 to 6 years (mean age 3.8±1.4 y) met inclusion criteria. The Spica group contained 91 patients; FIN contained 52 patients. Mean anesthetic exposure was less for Spica compared with FIN [45.1 min, 95% confidence interval (CI): 38.0-52.3 vs. 90.7 min, 95% CI: 80.5-100.8 min; P<0.001]. On average, Spica procedures required less fluoroscopy time compared with FIN (15.4 s, 95% CI: 4.8-26.0 vs. 131.6 s, 95% CI: 117.6-145.6 s; P<0.001). Mean radiation load was less for Spica compared with FIN (1.6 mGy, 95% CI: 0.6-2.6 vs. 6.9 mGy, 95% CI: 5.7-8.1 mGy; P<0.001). There was no difference in length of hospital stay (P=0.831), follow-up visits (P=0.248), or complication rate (P=0.645) between Spica and FIN groups. The most common complication was skin irritation for Spica (18.7%) and symptomatic hardware for FIN (17.3%)., Conclusions: The findings of this study suggest that pediatric patients with femoral shaft fractures experience an increased intraoperative burden when treated with FIN compared with Spica. Treatment with FIN was associated with increased exposure to anesthesia, fluoroscopic duration, and radiation load despite similar complication rates when compared with Spica., Level of Evidence: Level III., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purposes of this study were to assess the reproducibility of a novel standardized technique for capturing corneal subbasal nerve plexus images with in vivo corneal confocal microscopy and to compare nerve metrics captured with this method in participants with dry eye and control participants., Methods: Cases and controls were recruited based on their International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnoses. Participants completed the following 3 ocular symptom questionnaires: the Ocular Surface Disease Index, Neuropathic Pain Symptom Inventory, and Dry Eye Questionnaire 5. A novel eye fixation-grid system was used to capture 30 standardized confocal microscopy images of the central cornea. Each participant was imaged twice by different operators. Seven quantitative nerve metrics were analyzed using automated software (ACCmetrics, Manchester, United Kingdom) for all 30 images and a 6-image subset., Results: Forty-seven participants were recruited (25 classified as dry eye and 22 controls). The most reproducible nerve metrics were corneal nerve fiber length [intraclass correlation (ICC) = 0.86], corneal nerve fiber area (ICC = 0.86), and fractal dimension (ICC = 0.90). Although differences were not statistically significant, all mean nerve metrics were lower in those with dry eye compared with controls. Questionnaire scores did not significantly correlate with nerve metrics. Reproducibility of nerve metrics was similar when comparing the entire 30-image montage to a central 6-image subset., Conclusions: A standardized confocal imaging technique coupled with quantitative assessment of corneal nerves produced reproducible corneal nerve metrics even with different operators. No statistically significant differences in in vivo corneal confocal microscopy nerve metrics were observed between participants with dry eye and control participants., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Long-leg casts (LLCs) are an established treatment for pediatric tibial shaft fractures including fractures involving the distal third. There is a paucity of literature assessing the use of short-leg cast (SLC) for tibial shaft fractures. The purpose of this study was to determine if SLC were as effective as LLC for the treatment of pediatric distal third tibial shaft fractures., Methods: A retrospective review was conducted on consecutive distal third tibial shaft fractures treated at a tertiary pediatric hospital from 2013 to 2018. Exclusion criteria included midshaft and proximal fractures of the tibia, distal fractures that violated the tibial physis or plafond, and pathologic fractures. We compared primary outcomes of time to weight-bearing, time to union, and final angulation between LLC and SLC groups., Results: Eighty-five patients aged 5 to 17 years (mean age: 9.2±3.2 y) met inclusion criteria, including 50 LLC and 35 SLC patients. Time to weight-bearing for SLC (3.3±0.6 wk) was shorter compared with LLC (6.4±0.7 wk, P<0.0001). Overall, fractures treated with SLC had a shorter time to the union (7.4±0.9 wk) compared with LLC (9.0±0.9 wk, P=0.026) without statistical differences in final angulation at the time of union. There was a higher percentage of cast complications in the LLC treatment group (12%) compared with SLC (6%)., Conclusions: SLC demonstrated earlier time to weight-bearing and shorter time to fracture union when compared with LLC. Surgeons should consider SLC and early weight-bearing for the treatment of distal third tibial shaft fractures in children., Level of Evidence: Level III-retrospective comparative study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To develop a screening questionnaire to identify patients with dry eye with a high likelihood of having underlying Sjögren syndrome (SS)., Methods: This was a cross-sectional study of participants with dry eye complaints who were self-referred or referred by an ophthalmologist to the Sjögren's International Collaborative Clinical Alliance study. Symptoms and ocular surface examination findings were candidate predictors. Univariable and multivariable logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the association of a symptom and/or ocular sign with SS. Area under the receiver operating characteristic curve (AUC) was used to summarize the predictive ability of different regression models and the derived likelihood score., Results: Four questions were statistically significant in the final multivariable model: 1) Is your mouth dry when eating a meal? [Yes = OR 1.63 (1.18-2.26)]; 2) Can you eat a cracker without drinking a fluid or liquid? [No = OR 1.46 (1.06-2.01)]; 3) How often do you have excessive tearing? [None of the time = OR 4.06 (1.81-9.10)]; and 4) Are you able to produce tears? [No = OR 2.24 (1.62-3.09)]. The SS likelihood score had an AUC of 0.70 (95% CI, 0.66-0.73), and when including tear break-up time and conjunctival staining, it yielded an AUC of 0.79 (95% CI, 0.77-0.82)., Conclusions: This questionnaire can be used to identify patients with dry eye with a high likelihood of having SS. With future refinement and validation, this screening tool could be used alone or in combination with examination findings to identify patients with SS earlier, thereby facilitating better clinical outcomes., Competing Interests: V. Y. Bunya: Bausch & Lomb (funding for research study); Celularity (consultant); Verily (consultant). E. K. Akpek: Allergan Inc. (institutional support), Novalique Gmb. (consultant), Regeneron (consultant), Sjogren's Syndrome Foundation (unpaid board member). M. Massaro-Giordano: Celularity (consultant); PRN (personal financial interest); Verily (consultant). F. B. Vivino: Novartis (consultant), Biogen-Idec (consultant), Celularity (consultant), Boston Pharmaceuticals (consultant) Bristol-Myers Squibb (consultant), Immco Diagnostics (consultant). A. N. Baer: Bristol-Myers Squibb (consultant), Abbvie (consultant), Sanofi (consultant). The remaining authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Iridocorneal endothelial (ICE) syndrome is a group of rare ocular conditions that result from abnormal corneal endothelial cells, leading to secondary glaucoma, iris distortions, and corneal edema. The etiology of ICE is unknown, although it has been associated with viral infections, such as herpes simplex virus. In this study, we sought to identify an infectious etiology for ICE using advanced molecular techniques., Methods: Metagenomic RNA sequencing (MDS) is a high-throughput sequencing approach that can identify all pathogens in any clinical sample, including RNA viruses. Descemet membrane and aqueous fluid from patients with ICE syndrome were subjected to MDS testing., Results: Samples from 3 patients with ICE were analyzed. MDS was performed on the aqueous fluid of 3 patients and Descemet membrane and endothelial cell tissue from 1 patient. Viral pathogens were not identified in any of the samples., Conclusions: We were unable to identify a viral etiology in the tissues of patients with the Chandler variant of ICE syndrome, although this study was limited by sample size.

Purpose: To evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard., Methods: Cross-sectional study of participants from the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors., Results: A total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively., Conclusions: OSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

Purpose: Cytomegalovirus is an increasingly recognized cause of anterior uveitis. We present clinical features of cytomegalovirus anterior uveitis (CMVAU) and outcomes of oral valganciclovir treatment at a tertiary referral center in North America., Methods: This is a retrospective case series review (2002-2014) of immunocompetent patients with CMVAU treated with valganciclovir 900 mg BID and subsequent maintenance dosing of ≤450 mg BID. Most patients were prescribed topical corticosteroids concurrently. Diagnostic evaluations and clinical features at baseline and follow-up were reviewed. Resolution time, maintenance of quiescence, and adverse events were assessed., Results: Eighteen eyes of 16 patients were included. The mean age of diagnosis was 41 years. At diagnosis, mean best-corrected visual acuity was 0.30 LogMAR and mean intraocular pressure (IOP) was 18.4 mm Hg; 14 eyes (78%) had an active anterior chamber (AC) cell, 8 (44%) had circinate keratic precipitates, and 6 (33%) had iris atrophy. The mean follow-up duration was 48 months. Fourteen eyes of 12 patients were available for the 12-month follow-up; patients demonstrated improvement in best-corrected visual acuity (difference: -0.21 LogMAR, 95% CI -0.33 to -0.09; P = 0.003), AC cell (OR = 0.10, 95% CI 0.02-0.41; P = 0.002), and IOP (difference: -4.21 mm Hg, 95% CI -7.98 to -0.44; P = 0.03) compared with baseline. One patient experienced a serious adverse event likely due to valganciclovir. Thirteen eyes experienced recurrence of inflammation: 7 (54%) on prophylactic dose of valganciclovir and 6 (46%) after stopping., Conclusions: Valganciclovir appears effective and safe for treating CMVAU in this retrospective case series. Long-term antiviral prophylaxis does not abolish recurrences, although it may possibly reduce their frequency when compared with no prophylaxis.

Purpose: To evaluate the prevalence of novel candidate autoantibodies associated with Sjögren syndrome (SS) and their ability to identify those with SS among participants with dry eye enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) study at the University of Pennsylvania (Penn)., Methods: All participants previously underwent a full ocular and systemic evaluation for possible SS as part of the SICCA study. An enzyme-linked immunosorbent assay was used to detect IgG, IgA, and IgM autoantibodies to salivary protein 1 (SP-1), parotid secretory protein (PSP), and carbonic anhydrase 6 from previously banked baseline serum samples from SICCA study participants enrolled at Penn. The prevalence rate of each autoantibody, calculated by considering the presence of any isotype as antibody positive, was compared between participants with dry eye with SS (n = 81) or without SS (n = 129) using the Fisher exact test., Results: The prevalence of SP-1 IgM autoantibodies was higher in those with SS compared with those without SS (14% vs. 5%; P = 0.03). Similarly, the prevalence of PSP IgA autoantibodies was higher in those with SS compared with non-SS dry eye participants (21% vs. 11%; P = 0.048). There was no statistically significant difference in the prevalence of carbonic anhydrase 6 autoantibodies between those with or without SS (15% vs. 20%; P = 0.36)., Conclusions: In the Penn SICCA cohort, SP-1 IgM and PSP IgA autoantibodies were more prevalent in the serum of SS-related dry eye participants compared with those without SS. Further longitudinal studies are needed to determine the clinical significance of these findings.

Purpose of Review: Vitreoretinal lymphoma (VRL) is well known as a masquerade syndrome. However, delays in diagnosis are common particularly because of the small volume of tissue that is used for investigative studies. We outline the current diagnostic tests available to clinicians and provide a glimpse of possible future novel diagnostics., Recent Findings: The use of spectral domain ocular coherence tomography to identify subretinal lesions has proven to be a reliable ally to clinicians. Nevertheless, the diagnostic gold standard remains cytology, which requires a skilled pathologist. Molecular tests, including MYD88 polymerase chain reaction testing has further refined our diagnostic capabilities. Metagenomic deep sequencing is a newer molecular test that offers the ability to identify any mutation associated with lymphoma development and may offer more sensitive testing in the future., Summary: Clinicians have developed a strong acumen for suspecting VRL based upon clinical features, which can further be supported by a variety of imaging modalities. Delays in diagnosis continue to occur particularly because of the small volume of ocular fluid available for testing and because current tests offer a biased approach in terms of limited scope of detecting a specific mutation or cytopathologic feature(s). Newer molecular techniques feature an expanded scope of detecting any mutation associated with lymphomatous development.

Purpose of Review: This review highlights recent studies that have increasingly implicated cytomegalovirus (CMV) as a significant cause of keratouveitis and retinitis in immunocompetent hosts., Recent Findings: Molecular testing has identified that CMV infection is frequently present in cases of Posner-Schlossman and Fuchs, keratouveitis syndromes previously presumed to be idiopathic conditions. Ocular hypertension and endothelial cell loss are important complications of CMV keratouveitis and are likely mediated by viral invasion of the trabecular meshwork and corneal endothelium. Topical ganciclovir is a well tolerated, effective, and economical therapy. CMV retinitis is possible in the absence of HIV/AIDS., Summary: CMV has long been considered an innocuous infection in the general population, though recent studies have found otherwise. Intraocular reactivation, replication, and invasion of the trabecular meshwork and endothelium lead to recurrent bouts of ocular hypertension and endothelial cell loss, the complications of which may be tempered with initiation of antivirals. Topical ganciclovir is a promising therapy that needs investigation. CMV retinitis, an entity previously believed isolated to the severely immunosuppressed population, has been reported on numerous occasions in presumably immunocompetent individuals, particularly following local steroid injections. Further studies may elucidate the pathogenesis of CMV in immunocompetent populations.

Purpose of Review: This review offers recommendations for monitoring disease status in ocular cicatricial pemphigoid as well therapeutic options including local and systemic therapies., Recent Findings: A negative biopsy on direct immunofluorescence does not preclude a diagnosis of OCP. If a patient's cicatrization is active and/or progressive, systemic immunosuppression should be commenced., Summary: OCP is a chronic systemic autoimmune disease that requires systemic immunosuppression.

Purpose: To describe a case series of patients with unilateral, posterior interstitial keratitis presumed to be caused by herpes simplex virus., Methods: Retrospective case series., Results: Five patients were found to have unilateral, posterior interstitial keratitis. Three of the involved eyes had decreased corneal sensation, and 2 eyes had corneal stromal neovascularization. All patients were treated with topical steroids and an oral antiviral, and among those with long-term follow-up, clinical improvement required treatment over an extended duration. A review of the literature revealed 1 reported case with a similar clinical appearance, although that case was attributed to Lyme disease., Conclusions: The clinical presentation of unilateral, posterior interstitial keratitis may be a rare manifestation of herpes simplex virus keratitis.

Monteggia fractures comprise a small subset of fractures in the pediatric population that are normally reduced nonoperatively. Complex Monteggia fractures can be more difficult to identify and require operative intervention. We describe a case of a Bado type I Monteggia fracture with a posteriorly dislocated radial head and neck fracture that has not been described before in the literature. The patient required advanced imaging because of ossification delays and led to an operative intervention to reduce the radial head and neck. This case exemplifies how irreducible Monteggia fractures may necessitate advanced imaging to determine blocks to a successful reduction.

Objective: Previous research demonstrated that social environment can influence progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. This study examined the effect of social environment on markers of oxidative stress and inflammation to clarify the physiological pathways potentially responsible for the influence of social environment on disease., Methods and Results: WHHL rabbits were assigned to 1 of 3 social groups: an unstable group, in which unfamiliar rabbits were paired daily, with the pairing switched each week; a stable group, in which littermates were paired daily; and an individually-caged group. The stable group engaged in more affiliative social behavior than the unstable group. The unstable group showed more agonistic behavior compared with the stable group and higher C-reactive protein levels than the individually caged group. The individually caged group was behaviorally sedentary, had higher 24-hour urinary catecholamine levels than the other groups, and exhibited higher NAD(P)H-oxidase activity in the aortic arch relative to the stable group., Conclusions: The results suggest that social environment creates distinct behavioral contexts that can affect markers of inflammation and oxidative stress early in the development of atherosclerosis. Specifically, physical inactivity associated with individual caging affects indices of oxidative stress and inflammation. These pathophysiological markers may help to explain behaviorally related differences in the extent of atherosclerosis observed in prior studies.

Objective: A previous study suggested that insulin metabolic variables play a role in the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. The present study sought to determine: 1) if young, individually caged WHHLs are insulin-resistant relative to New Zealand white (NZW) rabbits and 2) whether dietary or exercise interventions can improve insulin sensitivity and slow the development of atherosclerosis in these animals., Methods: Forty-two WHHLs were assigned to a dietary, exercise, or control condition, and 12 NZWs were used as a comparison control group. The intervention ran from 3 to 7 months of age, and all animals received an intravenous glucose tolerance test at the beginning and end of the intervention., Results: WHHLs were insulin-resistant relative to NZWs at 3 months of age. Whereas the dietary intervention was effective in controlling insulin resistance, WHHLs in the exercise group without dietary restriction and the control group exhibited significant increases in insulin resistance. No intervention significantly influenced the progression of atherosclerosis., Conclusions: Young WHHLs are insulin-resistant during an early period when atherosclerosis is developing rapidly. Dietary restriction, but not exercise without weight control, is effective in controlling insulin metabolic variables in the WHHL model. Although dietary intervention can reduce cardiovascular risk factors such as insulin resistance, it is not effective in slowing the development of atherosclerosis in these genetically dyslipidemic animals. Similarly, exercise training, without dietary control, does not influence the progression of disease in WHHLs.

Background: Although there is evidence that emotionally stressful behavior can accelerate the progression of atherosclerosis, there is less data to support the notion that affiliative social behavior can slow disease progression. The present study examines the influence of social environment on the progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit, a model that spontaneously develops lesions because of a genetic defect in lipoprotein clearance., Methods and Results: WHHL rabbits were assigned to 1 of 3 social or behavioral groups: an unstable group, in which unfamiliar rabbits were paired daily, with the pairing switched each week; a stable group, in which littermates were paired daily for the entire study; and an individually caged group. The stable group exhibited more affiliative social behavior and less agonistic behavior than the unstable group and significantly less aortic atherosclerosis than each of the other 2 groups. Although the unstable and individually caged groups had comparable aortic lesion areas, the severity of the disease progressed faster in the unstable group, as indexed by a larger area of calcification and increased fibrous cap thickness in complex lesions. The unstable group showed increased agonistic behavior and signs of chronic adrenocortical and gonadal activation, whereas the individually caged group was relatively sedentary, had low glucocorticoid levels, and was hyperinsulinemic compared with the other groups., Conclusions: The present study demonstrates that social environment can slow, as well as accelerate, the progression of atherosclerosis. It also emphasizes the importance of behavioral factors in atherogenesis, even in a model of disease with strong genetic determinants.