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BACKGROUND: The rate of cytomegalovirus (CMV) retinitis is increasing, likely secondary to aggressive immunosuppressive regimens for a variety of diseases. Transplant and rheumatological literature show growing evidence suggesting a unique relationship between CMV infection and mycophenolate in particular. This study reports two cases of CMV retinitis infection in patients on mycophenolate immunosuppression. CASE PRESENTATION: Case A was a 39-year-old African American woman with systemic lupus erythematosus (SLE) with stage IV lupus nephritis who presented for bilateral retinal detachments with areas of moth-eaten and thin retina concerning for prior viral retinitis. Case B was a 53-year-old man who presented with floaters in the right eye status-post heart transplant since 2008 on immunosuppressive therapy. Fundoscopic examination of the right eye showed frosted branch angiitis with intraretinal hemorrhage and inner retinal thickening and disorganization, consistent with CMV retinitis infection. Both patients were on mycophenolate immunosuppression with the recommendation to reduce or discontinue mycophenolate. CONCLUSION: Patients on mycophenolate immunosuppression may be more vulnerable to cytomegalovirus infection, including CMV retinitis. Ophthalmologists should be aware of this increased risk and consider reducing or discontinuing mycophenolate to promote viral clearance in these susceptible patients, in conjunction with the patients transplant or rheumatology teams.

KEY CLINICAL MESSAGE: Prompt diagnosis and treatment of GCA are crucial to preserve vision. Because of this, new-onset ptosis or diplopia in elderly patients should warrant consideration of GCA, even in the absence of classic features, systemic symptoms or elevated inflammatory markers. ABSTRACT: Giant cell arteritis (GCA) is a vision-threatening, ophthalmic emergency that classically presents with new-onset headaches, scalp tenderness, systemic symptoms, visual disturbances, and elevated inflammatory markers. We describe an atypical presentation of GCA in an 87-year-old patient with fatigable ptosis and diplopia, with subsequent anterior ischemic optic neuropathy and choroidal infarction.

BackgroundCone contrast threshold testing (CCT) provides quantitative measurements of color and contrast function to reveal changes in vision quality that are not standard endpoints in clinical trials. We utilize CCT to measure visual function in patients with multiple sclerosis (MS), age-related macular degeneration (AMD), epiretinal membrane (ERM), and retinal vein occlusion (RVO).MethodsRetrospective data was gathered from 237 patients of the Gavin Herbert Eye Institute. Subjects included 17 patients with MS, 45 patients with AMD, 41 patients with ERM, 11 patients with RVO, and 123 healthy controls. Patients underwent the primary measurement outcome, CCT testing, as well as Sloan visual acuity test and spectral domain optical coherence tomography during normal care.ResultsColor and contrast deficits were present in MS patients regardless of history of optic neuritis. AMD with intermediate or worse disease demonstrated reduced CCT scores. All 3 stages of ERM demonstrated cone contrast deficits. Despite restoration of visual acuity, RVO-affected eyes demonstrated poorer CCT performance than unaffected fellow eyes.ConclusionsCCT demonstrates color and contrast deficits for multiple retinal diseases with differing pathophysiology. Further prospective studies of CCT in other disease states and with larger samples sizes is warranted.

PurposeLong-acting injectable fluocinolone releasing implants are used in clinical practice. Although limited in scope, situations may arise where removal of the implant is warranted. We set out to describe possible explantation techniques and to determine whether these implants can be safely removed from a standard sclerotomy or eliminated using a vitrectomy system.MethodsA vitreoretinal surgery system was designed using a porcine eye model. A fluocinolone implant was injected into the vitreous cavity. Pars plana vitrectomy was performed and the vitreous cavity was infused with balanced salt solution. The injected implants were removed from 23-Gauge (G) and 25-Gauge (G) vitrectomy cannulas with 27-G forceps. The implants were examined under the microscope for induced defects. Implants were injected into the eye model and eliminated using a 23-G and 25-G vitrector system.ResultsThe implant was removed from both the 23-G and 25-G vitrectomy cannulas with only mild structural damage to the implant. During implant extraction through the 25-G sclerotomy, the cannula was dislodged from the incision along with the implant. The most technically challenging portion involved aligning the implant coaxially to allow for removal en bloc through the sclerotomy site. Implants could be eliminated using both the 23-G and 25-G vitrector using a low-cut rate.ConclusionThe fluocinolone implant was removed safely via standard 23-G or 25-G vitrectomy systems. It is unknown whether intraocular manipulation will affect pharmacokinetics of drug delivery if the implant is not explanted.

Background and Objective: Vitreoretinal surgery requires fine micro-surgical training and handling of delicate tissue. To aid in the training of residents and fellows, unique educational modalities exist to help facilitate the development of these microsurgical skills. From virtual simulators to artificial eye models, simulation of the posterior segment has gained an increased focus in vitreoretinal surgical training programs. Development of surgical curricula for vitreoretinal training and attainment of surgical milestones has been a key component in integrating these educational training modalities. We will explore various simulators, eye models, and potential rubrics and discuss unique ways each may help and complement one another to train future vitreoretinal surgeons. Methods: We conducted a systematic PubMed search of various review studies (from publications in English ranging from January 1978 to December 2020) discussing surgical simulators, eye models, and surgical rubrics for vitreoretinal surgery and their potential impacts upon training. Key Contents and Findings: Our review assesses the benefits and applicability of various simulators, eye models, and surgical rubrics upon training. Conclusions: Utilization of vitreoretinal surgical training tools may aid in complementing the hands-on surgical training experience for vitreoretinal surgical fellows. By using simulators and rubrics, we may better be able to standardize training for reaching vitreoretinal surgical milestones and providing adequate feedback to improve surgical competency and ultimately patient outcomes.

Order entry via mobile client was associated with decreased after-hours EHR use in a cohort of 139 academic ophthalmologists. EHR audit log data can provide insights into strategies for optimizing efficiency of EHR use.

PURPOSE: We report a case of advanced metastatic cutaneous melanoma with melanoma-associated retinopathy and pembrolizumab-related panuveitis and optic neuritis. METHODS: The patients condition was managed by systemic, topical, and intravitreal corticosteroids without discontinuing pembrolizumab. RESULTS: After initiation of systemic and topical steroid treatment, optic nerve edema improved. He developed chronic uveitis with cystoid macular edema with improvement in symptoms with intravitreal dexamethasone implants. The patient demonstrated a decrease in all metastatic lesions and improvement in melanoma-associated retinopathy. CONCLUSIONS: The new checkpoint inhibitor class including pembrolizumab shows promise as a therapy for advanced metastatic melanoma in patients resistant to all other forms of chemotherapy. In general, immune-related adverse effects are responsive to steroid therapy. The trend for treatment of posterior uveitis due to pembrolizumab is to discontinue pembrolizumab. Our case suggests that even severe cases of uveitis may be sufficiently ameliorated by concurrent systemic, intravitreal, and topical therapy to allow continuation of treatment.

Vitreopapillary traction (VPT) syndrome is a potentially visually significant disorder of the vitreopapillary interface characterised by an incomplete posterior vitreous detachment with the persistently adherent vitreous exerting tractional pull on the optic disc and resulting in morphologic alterations and a consequent decline of visual function. It is most commonly unilateral but bilateral reports have also been described. The cause of the condition may be unknown or idiopathic, although the histology of traction shows proliferation of fibrous astrocytes, myofibroblasts, fibrocytes, and retinal pigment epithelial cells. It is theorised that VPT may induce a congested optic disc with neuronal dysfunction as well as decreased prelaminar flow. The present study reviews and summarises the features, diagnosis, and management of VPT.

BACKGROUND:Refractory non-infectious uveitis is a serious condition that leads to ocular complications and vision loss and requires effective systemic treatment to control disease. The effectiveness of long-term infliximab [IFX] in refractory non-infectious childhood uveitis and the impact of treatment adherence on disease control were evaluated. METHODS:Retrospective, single-center study between December 2002 and April 2016 of 27 children with refractory non-infectious uveitis [17 with juvenile idiopathic arthritis, JIA] treated with long-term IFX [9+ months]. Disease activity was assessed prior to and while on IFX using the Standardization of Uveitis Nomenclature [SUN]. Number of visits per year with active uveitis was analyzed by repeated measures logistic regression analysis from 2 years prior to IFX initiation or from onset of uveitis until most recent visit on IFX. Incomplete treatment adherence was assessed for each visit and defined as any deviance in corticosteroid use, prescribed infusion frequency, and/or follow-up examination frequency. RESULTS:Primary outcomes were sustained uveitic and systemic disease control prior to and during IFX treatment and the impact of incomplete adherence on uveitic disease control while on IFX. Secondary outcomes included corticosteroid and glaucoma medication requirement, ocular complications and need for surgical intervention. Mean age at IFX initiation was 10.4 ± 4.5 years; initial mean dose was 6.6 ± 2.2 mg/kg [and given at weeks 0, 2, 4 and q4 weeks thereafter for 93%]. Median duration on IFX was 35 [range 9-128] months. Prior to IFX, 14/27 patients had failed adalimumab ± methotrexate [MTX]; 21/27 failed MTX. IFX led to uveitis control in 89% and arthritis control in 76% (13/17). The odds ratio of having controlled disease after IFX was 4.1 (2.6, 6.4) compared to pre-treatment visits. Topical corticosteroids and glaucoma medications were statistically decreased (p = 0.007 right eye [OD], 0.003 left eye [OS] and p = 0.001 OD, p = 0.028 OS respectively). Incomplete adherence to treatment showed 10.3 times greater odds (7.1, 15.0) of having disease activity than full adherence. CONCLUSIONS:This study adds significantly to the IFX literature by documenting outstanding uveitis control with long-term IFX treatment in non-infectious pediatric uveitis patients. Higher dosage and shorter interval were utilized without adverse effects. Importantly, this is the first study, to our knowledge, to document the significant impact of treatment adherence on uveitis control.

ObjectiveNeuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.MethodsCortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).ResultsIn the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.ConclusionsSubtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

BackgroundPrader-Willi syndrome (PWS) is a genetic disease caused by loss of expression of the paternally inherited copy of several genes on the long arm of chromosome 15. Ophthalmic manifestations of PWS include strabismus, amblyopia, nystagmus, hypopigmentation of the iris and choroid, diabetic retinopathy, cataract and congenital ectropion uvea. An overlap between PWS and oculocutaneous albinism (OCA) has long been recognized and attributed to deletion of OCA2 gene located in PWS critical region (PWCR).Case reportA 30-year-old male patient with PWS presented with vision loss in his left eye. His right eye had normal visual acuity. Multimodal imaging revealed absence of a foveal depression and extremely reduced diameter of the foveal avascular zone in the right eye and an inactive type 2 macular neovascular lesion in the left eye.ConclusionsWe report a presumed association of fovea plana and choroidal neovascularization with PWS. The use of multimodal imaging revealed novel findings in a PWS patient that might enrich our current understanding of the overlap between PWS and OCA.

BackgroundVisual impairment in developing countries has both social and economic impact on individuals and communities. Understanding the subjective visual functioning of populations will allow for local policymakers to identify the need for optometric or ophthalmic services in their communities.MethodsThe authors surveyed 644 adult patients in Mwanza, Tanzania at three clinics (Buzuruga, Mwananchi and Kisesa) using a modified Visual Functioning Questionnaire 25. Responses were categorized into General health, General vision, Ocular pain, Near activities, Distance activities, Social function, Mental health, Role difficulties, Color vision, Peripheral vision and Dependency.ResultsPatients at Buzuruga reported the lowest scores on most subscales. Of 100 employed patients, 37% claimed to have at least some difficulty in performing job duties due to their eyesight. At Kisesa, 146 (246/221) patients (66.1%) had never had an eye exam, compared with 134/227 (59.0%) at Buzuruga and 69/173 (39.9%) at Mwananchi (p

Disruptions in social decision-making are becoming evident in many psychiatric conditions. These are studied using paradigms investigating the psychological mechanisms underlying interpersonal interactions, such as the Ultimatum Game (UG). Rejection behaviour in the UG represents altruistic punishment - the costly punishment of norm violators - but the mechanisms underlying it require clarification. To investigate the psychopharmacology of UG behaviour, we carried out two studies with healthy participants, employing serotonergic agonists: psilocybin (open-label, within-participant design, N = 19) and 3,4-methylenedioxymethamphetamine (MDMA; placebo-controlled, double-blind, crossover design, N = 20). We found that both MDMA and psilocybin reduced rejection of unfair offers (odds ratio: 0.57 and 0.42, respectively). The reduction in rejection rate following MDMA was associated with increased prosociality (R2 = 0.26, p = 0.025). In the MDMA study, we investigated third-party decision-making and proposer behaviour. MDMA did not reduce rejection in the third-party condition, but produced an increase in the amount offered to others (Cohen's d = 0.82). We argue that these compounds altered participants' conceptualisation of 'social reward', placing more emphasis on the direct relationship with interacting partners. With these compounds showing efficacy in drug-assisted psychotherapy, these studies are an important step in the further characterisation of their psychological effects.

Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans.