A fluorescein angiography-based computer-aided algorithm for assessing the retinal vasculature in diabetic retinopathy.

OBJECTIVE: To present a fluorescein angiography (FA)‒based computer algorithm for quantifying retinal blood flow, perfusion, and permeability, in patients with diabetic retinopathy (DR). Secondary objectives were to quantitatively assess treatment efficacy following panretinal photocoagulation (PRP) and define thresholds for pathology based on a new retinovascular function (RVF) score for quantifying disease severity. METHODS: FA images of 65 subjects (58 patients and 7 healthy volunteers) were included. Dye intensity kinetics were derived using pixel-wise linear regression as a measure of retinal blood flow, perfusion, and permeability. Maps corresponding to each measure were then generated for each subject and segmented further using an ETDRS grid. Non-parametric statistical analyses were performed between all ETDRS subfields. For 16 patients, the effect of PRP was measured using the same parameters, and an amalgam of RVF was used to create an RVF index. For ten post-treatment patients, the change in FA-derived data was compared to the macular thickness measured using optical coherence tomography. RESULTS: Compared to healthy controls, patients had significantly lower retinal and regional perfusion and flow, as well as higher retinal permeability (p < 0.05). Moreover, retinal flow was inversely correlated with permeability (R = -0.41; p < 0.0001). PRP significantly reduced retinal permeability (p < 0.05). The earliest marker of DR was reduced retinal blood flow, followed by increased permeability. FA-based RVF index was a more sensitive indicator of treatment efficacy than macular thickness. CONCLUSIONS: Our algorithm can be used to quantify retinovascular function, providing an earlier diagnosis and an objective characterisation of disease state, disease progression, and response to treatment.

A 2020 Update on 20/20 X 2: Diplopia after Inadvertent Strabismus Surgery Complications.

The goals of successful strabismus surgery include the optimization of binocular potential through the establishment, reestablishment, or improvement of ocular alignment leading to a reduction or resolution of diplopia, as well as an improvement of compensatory head position or cosmesis. Fortunately, the incidence of new postoperative diplopia in patients without diplopia prior to strabismus surgery is extremely uncommon (less than 2%). Alternatively in a patient with preoperative diplopia that persists postoperatively, it is important to establish whether the diplopia is unchanged, increased, or of the same magnitude but shifted to a more disruptive position of gaze. During preoperative planning, the surgeon tries to anticipate and thus avoid postoperative diplopia. If the postoperative diplopia is unexpected, then a dispassionate evaluation of the outcome to identify planning, mechanical, or other factors is necessitated. These factors will be explored below systematically in the preoperative, intraoperative, and postoperative phases.

MRI Characteristics of NMO, MOG and MS Related Optic Neuritis.

Acute isolated optic neuritis can be the initial presentation of demyelinating inflammatory central nervous system disease related to multiple sclerosis (MS), neuromyelitis optica (NMO) or myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). In addition to the well-characterized brain and spinal cord imaging features, important and characteristic differences in the radiologic appearance of the optic nerves in these disorders are being described, and magnetic resonance imaging (MRI) of the optic nerves is becoming an essential tool in the differential diagnosis of optic neuritis. Whereas typical demyelinating optic neuritis is a relatively mild and self-limited disease, atypical optic neuritis in NMO and MOG-AD is potentially much more vision-threatening and merits a different treatment approach. Thus, differentiation based on MRI features may be particularly important during the first attack of optic neuritis, when antibody status is not yet known. This review discusses the optic nerve imaging in the major demyelinating disorders with an emphasis on clinically relevant differences that can help clinicians assess and manage these important neuro-ophthalmic disorders. It also reviews the utility of optic nerve MRI as a prognostic indicator in acute optic neuritis.

Effect of Topical Corticosteroids on Early Postoperative Intraocular Pressure Following Combined Cataract and Trabecular Microbypass Surgery.

Purpose: To evaluate the early postoperative outcomes of trabecular micro-bypass stents and concomitant cataract surgery (TMS-CS) with and without postoperative corticosteroid therapy. Methods: Prospective, interventional matched, consecutive case series comparing outcomes of open-angle glaucoma patients who underwent TMS-CS with and without postoperative corticosteroid therapy. Primary outcome was intraocular pressure (IOP) changes up to 6 months postoperatively and the secondary outcomes included number of postoperative medications, IOP spikes, peripheral anterior synechia (PAS), and best-corrected visual acuity improvements. Results: The clinical outcomes of 97 eyes-49 in the steroid group age- and IOP-matched with 48 in the nonsteroid group-were analyzed. Baseline IOP in steroid and nonsteroid groups were 16.22 ± 3.98 and 16.04 ± 3.99 (P = 0.822), respectively. Both IOP and number of antiglaucoma medications significantly decreased postoperatively (P < 0.001), however, there were no group differences at different time points (P = 0.653 and P = 0.168, respectively). At 1 week postoperatively, the steroid group had higher number of IOP spikes (n = 9) compared with nonsteroid group (n = 2, P = 0.022). There was no significant difference in postoperative PAS between the steroid group (n = 6) and nonsteroid group (n = 6, P = 0.970). Vision improved significantly postoperatively (P < 0.001) with no group differences at different time points (P = 0.322). Conclusions: TMS-CS decreased IOP and number of antiglaucoma medications while improving visual acuity both with and without the use of postoperative steroids. Limiting the use of postoperative steroids in combined microbypass stents and cataract surgery appears to be a safe surgical option and may help minimize acute elevations in IOP in the early postoperative period.

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder.

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme's metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher's can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 - present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

Transient myopic shift due to ciliary body detachment as the sole ocular manifestation of hypertensive emergency - A case report.

PURPOSE: Hypertensive emergency usually presents to ophthalmologists in the form of hypertensive retinopathy. We present a case of hypertensive emergency that presented as bilateral transient myopic shift due to ciliary body detachment in the absence of any retinal pathology. The purpose of this paper is to showcase another ocular manifestation of hypertensive emergency. OBSERVATIONS: A 35 year-old female with a blood pressure of 192/114 mmHg presented to the emergency department with headache and acute onset blurry vision. Computed Tomography (CT) of the head, and lumbar puncture were within normal limits. Visual acuity was counting fingers in the right eye and 6/90 in the left eye, both of which improved to 6/9 with -5.00 diopters spherical correction in the right eye, and -4.75 diopters correction in the left eye. Intraocular pressures were normal. Anterior chambers were shallow, and there were no retinal changes on dilated fundus examination. Enhanced-depth optical coherence tomography (EDI-OCT) showed bilateral increased choroidal thickness and ultrasound biomicroscopy (UBM) showed 360° ciliary body detachment with angle closure. With improved blood pressure control, her ciliary body detachment resolved and her refractive error returned to baseline. CONCLUSIONS: & Importance: Hypertensive emergency may present with choroidal thickening with anterior ciliary body rotation and detachment. A review of medications is important, as this presentation has also been reported as a rare side effect of sulphonamide drugs. In the absence of retinopathy, UBM and EDI-OCT imaging should be considered in the acutely hypertensive patient presenting with myopic shift.

Plasma Amino Acids vs Conventional Predictors of Insulin Resistance Measured by the Hyperinsulinemic Clamp.

CONTEXT: Specific plasma amino acid (AA) profiles including elevated postabsorptive branched-chain amino acids (BCAAs) have been associated with insulin resistance (IR), mostly estimated by homeostatic model assessment. This study assessed the associations of postabsorptive AAs with IR directly measured by insulin-mediated glucose disposal and determined the quantitative value of AAs and conventional IR predictors. DESIGN: Fifty-one healthy, 31 overweight or obese (Ow/Ob), and 52 men and women with type 2 diabetes (T2D) were studied retrospectively. The main outcome measures were the glucose disposal (M/I) index (using 3-[3H]-glucose) during a hyperinsulinemic-euglycemic clamp and whole-body protein turnover (using 1-[13C]-leucine). RESULTS: Compared with healthy participants, M/I was lower in Ow/Ob participants and lowest in those with T2D. BCAAs, glutamate, and lysine were higher in the Ow/Ob and T2D groups than in healthy participants; glycine and threonine were lower. Most AAs were higher in men. Principal component analysis identified component 1 (C1: BCAAs, methionine) and C3 (glycine, threonine, serine). Glutamate, C1, ornithine, lysine, methionine, and tyrosine correlated negatively with M/I; C3 and glycine correlated positively. Waist circumference and sex strongly influenced AA-IR relationships; only glutamate correlated after these factors were controlled for. From regression analysis, waist circumference, fasting glucose, insulin, and free fatty acids (FFAs) negatively predicted 64% of the M/I variance; glutamate added 2% more. In nondiabetic participants, IR was predicted by waist circumference, insulin, and FFAs, without contribution from AAs. CONCLUSION: Several postabsorptive AAs correlated with IR but added limited predictive value to conventional markers because levels were determined largely by abdominal adiposity. Data suggest a sex-specific regulation of AA metabolism by excess adiposity, particularly the BCAAs, warranting investigation.

Angiographic evidence of proliferative retinopathy predicts neuropsychiatric morbidity in diabetic patients.

INTRODUCTION: Diabetic retinopathy (DR) is a common vasculopathy categorized as either non-proliferative (NPDR) or proliferative (PDR),characterized by dysfunctional blood-retinal barrier (BRB) and diagnosed using fluorescein angiography (FA). Since the BRB is similar in structure and function to the blood-brain barrier (BBB) and BBB dysfunction plays a key role in the pathogenesis of brain disorders, we hypothesized that PDR, the severe form of DR, is likely to mirror BBB damage and to predict a worse neuropsychiatric outcome. METHODS: A retrospective cohort study was conducted among subjects with diabetes (N=2982) with FA-confirmed NPDR (N=2606) or PDR (N=376). Incidence and probability to develop brain pathologies and mortality were investigated in a 10-year follow-up study. We used Kaplan-Meier, Cox and logistic regression analyses to examine association between DR severity and neuropsychiatric morbidity adjusting for confounders. RESULTS: Patients with PDR had significantly higher rates of all-cause brain pathologies (P<0.001), specifically stroke (P=0.005), epilepsy (P=0.006) and psychosis (P=0.024), and a shorter time to develop any neuropsychiatric event (P<0.001) or death (P=0.014) compared to NPDR. Cox adjusted hazard ratio for developing all-cause brain impairments was higher for PDR (HR=1.37, 95% CI 1.16-1.61, P<0.001) which was an independent predictor for all-cause brain impairments (OR 1.30, 95% CI 1.04-1.64, P=0.022), epilepsy (OR 2.16, 95% CI 1.05-4.41, P=0.035) and mortality (HR=1.35, 95% CI 1.06-1.70, P=0.014). CONCLUSIONS: This is the first study to confirm that angiography-proven microvasculopathy identifies patients at high risk for neuropsychiatric morbidity and mortality.

Do patients with advanced cancer have any potential for protein anabolism in response to amino acid therapy?

PURPOSE OF REVIEW: There is evidence that protein anabolism is achievable before cancer evolves into refractory cachexia with attenuation of muscle loss and even muscle gain. This review summarizes recent observations on the role of total and specific amino acids in promoting protein anabolism in human cancer and revisits prior studies in this context. RECENT FINDINGS: Analysis of muscle changes in advanced cancer patients indicated opportunities for inducing anabolism. Maintenance and gain in muscle was reported in a majority of patients, from initiation of oncologic treatment and before the final refractory stage. In addition to being substrates, some amino acids, for example leucine, act as intracellular signals to promote protein synthesis. Recent acute studies demonstrated that provision of amino acids, sufficient to considerably elevate circulating leucine concentrations concurrent with other amino acid and nutrient availability, resulted in significant protein anabolism in cancer patients. This occurred even during weight loss and inflammation. SUMMARY: Patients with cancer have an anabolic potential to be exploited early on in cachexia development. High-leucine and protein supplements are worth testing as part of a multimodal anabolic approach in long-term trials to confirm their efficacy to sustain anabolism, and attenuate or even reverse muscle wasting.

Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia.

BACKGROUND & AIMS: Insulin resistance of protein anabolism has been speculated to underlie the skeletal muscle wasting characteristic of cancer cachexia. We tested whether insulin resistance is present in cachectic lung cancer patients and if a sustained, physiological elevation of amino acids with hyperinsulinemia would compensate for it. METHODS: Whole-body [(13)C]leucine and [(3)H]glucose kinetics were assessed in 10 male non-small cell lung cancer (NSCLC) patients and 10 healthy matched controls during a euglycemic, hyperinsulinemic clamp under conditions of isoaminoacidemia followed by hyperaminoacidemia. RESULTS: Postabsorptive glucose and protein kinetics were comparable between groups. Glucose uptake was significantly lower in NSCLC patients during hyperinsulinemia. During concurrent isoaminoacidemia, protein breakdown was suppressed in both, but rates were elevated in NSCLC; rates of synthesis did not change, resulting in reduced net protein balance (synthesis - breakdown) in response to insulin in NSCLC. With subsequent hyperaminoacidemia, synthesis increased significantly with no further change in breakdown, resulting in similar increase in net balance between groups. CONCLUSIONS: NSCLC patients with moderate cachexia showed considerable insulin resistance of glucose and of whole-body protein anabolism. Their anabolic protein response was stimulated normally by hyperaminoacidemia. Thus, ample provision of amino acids is a feasible strategy to overcome the protein anabolic failure of cancer cachexia.

Changes in type of foodservice and dining room environment preferentially benefit institutionalized seniors with low body mass indexes.

OBJECTIVE: To compare energy intakes in seniors with cognitive impairment residing in long-term care and receiving meals by bulk (cafeteria style with waitress service) vs traditional tray delivery systems and determine subject characteristics that identify responsiveness to type of foodservice provided. DESIGN AND SUBJECTS/SETTING: Usual energy intakes were compared in subjects residing in cognitive impairment units in either the old (tray delivery, n=23) or new (bulk delivery, n=26) nursing home at Baycrest, a teaching facility associated with University of Toronto Medical School. INTERVENTION: Changes to foodservice and physical environment (from institutional to more home-like environment). MAIN OUTCOME MEASURES: Twenty-one consecutive day investigator-weighed energy and macronutrient intakes and behavioral function (London Psychogeriatric Rating Scale). STATISTICAL ANALYSES PERFORMED: Analysis of variance determined mean differences in intake and regression analyses identified predictors of sensitivity to type of food delivery systems. RESULTS: Higher 24-hour total (P<0.001) and dinner (P<0.001) energy intakes in subjects receiving bulk compared to tray delivery were predominantly associated with greater carbohydrate intakes (P<0.001). Higher energy, carbohydrate, and protein, but not fat intakes, with bulk delivery were more apparent in individuals with lower body mass indexes (BMIs) (food delivery by BMI interaction, all P values <0.05). CONCLUSIONS: High-risk, cognitively impaired individuals with low BMI benefited the most from the changed foodservice and physical environment, whereas individuals with higher BMIs did not show substantive changes in intake. Bulk foodservice and a home-like dining environment optimize energy intake in individuals at high risk for malnutrition, particularly those with low BMIs and cognitive impairment.