The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Advanced OCT Analysis of Biopsy-proven Vitreoretinal Lymphoma.

PURPOSE: Although diagnosing vitreoretinal lymphoma (VRL) can be challenging, early detection is critical for visual prognosis. We analyzed the spectrum of optical coherence tomography (OCT) findings in patients with biopsy-proven VRL and correlate these features with clinical parameters. DESIGN: This retrospective cross-sectional study was a multicenter chart review from 13 retina, uveitis, and ocular oncology clinics worldwide from 2008 to 2019. We included patients with a diagnosis of biopsy-proven VRL imaged with OCT at presentation. Ocular information, systemic information, and multimodal retinal imaging findings were collected and studied. The main outcome measure was the characteristics of VRL on OCT. RESULTS: A total of 182 eyes of 115 patients (63 women, mean age 65 years) were included in this study. The disease was bilateral in 81 patients (70%), and mean baseline visual acuity was 0.2 ± 0.89 logMAR (Snellen equivalent, 20/32). At baseline, 38 patients (33%) presented with isolated ocular involvement, 54 (45%) with associated central nervous system involvement, and 11 (10%) with other systemic lymphomatous involvement; an additional 12 patients (10%) presented with central nervous system and other systemic involvement. On OCT, tumor infiltration was identified in various retinal layers, including lesions in the subretinal pigment epithelium compartment (91% of eyes), the subretinal compartment (43% of eyes), and the intraretinal compartment (7% of eyes). OCT analysis of eyes with VRL identified 3 main regions of retinal infiltration. Subretinal pigment epithelium location, with or without subretinal infiltration, was the most common pattern of involvement and isolated intraretinal infiltration was the least.

Novel mechanism of decreased iris vasculature density after cosmetic iris implants.

A 25-year-old man presented with decreased vision in both eyes, approximately 4 years following bilateral bright ocular cosmetic iris implantation. On examination, he was found to have bilateral elevated intraocular pressures, anterior chamber cells and flare, chronic peripheral anterior synechiae and significantly reduced endothelial cell counts. Ultrasound biomicroscopy demonstrated compression of the peripheral iris, resulting in synechial angle closure in both eyes. Surgical removal of the implants was performed without additional complication. On removal, bilateral iris atrophy was evident with non-reacting pupils and permanent mydriasis. Optical coherence tomography angiography showed a reduction in iris vasculature density that is more pronounced in the area of the iris atrophic defects. This case suggests that cosmetic iris implants may compress iris vasculature, resulting in decreased iris perfusion resulting in atrophic mydriasis and iris defects. This is a potential novel mechanism for complications in eyes with cosmetic iris implants.

CHOROIDAL GRANULOMAS VISUALIZED BY SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess the visualization of choroidal granulomas with swept-source optical coherence tomography angiography (OCTA). METHODS: Consecutive patients with granulomatous choroiditis due to tuberculosis, sarcoidosis, or Vogt-Koyanagi-Harada disease underwent baseline OCTA images using a 12 × 12-mm field of view, and the choroidal slabs were analyzed by two independent examiners who counted the oval areas of flow void. Simultaneously, indocyanine green angiography (ICGA) and enhanced-depth imaging OCT were performed to mark visible choroidal changes corresponding to granulomatous lesions. The lesion areas on OCTA and ICGA were assessed using the in-built caliper tool. RESULTS: Three hundred and one round-shaped areas of flow void on OCTA, 209 hypofluorescent round lesions on ICGA, and 42 hyporeflective choroidal lesions on enhanced-depth imaging OCT were identified in 23 eyes from 14 patients. Of the 209 ICGA granulomas, 197 (94.3%) had a corresponding round area of flow void on OCTA that was interpreted as a granuloma. One hundred and four additional round flow voids were identified on OCTA that did not correspond to any hypofluorescent lesion on ICGA. The mean area of the 197 granulomas detected with both imaging modalities was significantly larger on ICGA (mean 0.33 mm2) than that on OCTA (mean 0.28 mm2). CONCLUSION: Optical coherence tomography angiography seems to be an optimal imaging method for the visualization of choroidal granulomas.

Screening for Keratoconus in a High-Risk Adolescent Population.

PURPOSE: To estimate the prevalence of keratoconus (KC) in a majority-Emirati adolescent population and to demonstrate the feasibility of screening using a dual Scheimpflug and Placido imaging device. METHODS: Adolescent subjects from two secondary schools in Abu Dhabi, UAE underwent corneal imaging with the Galilei tomographer (Ziemer Ophthalmic Systems AG, Port, Switzerland). The prevalence of KC and KC suspects was determined using a combination of both subjective and objective criteria. Objective criteria included these KC indices: percent probability of keratoconus, inferior-superior index, asphericity asymmetry index, maximum keratometry and thinnest pachymetry. Subjective pattern analysis was performed by four experienced cornea specialists. Subjects were classified by each cornea specialist into three groups: normal, KC and KC suspect. The final classification was made by group reconciliation of cases where disagreement was present. Inter-observer agreement was assessed with the kappa statistic. RESULTS: A total of 839 eyes of 420 students between 10 and 19 years of age underwent corneal tomography. After the exclusion of 251 eyes due to insufficient scan quality based on internal instrument-derived standards, 588 eyes of 339 subjects were included in the analysis. The prevalence of KC and KC suspect was estimated to be 2.7% (95% CI [1.2%, 5.0%]) and 19.8% (95% CI [15.7%, 24.4%]), respectively. There was a strong inter-observer agreement between examiners' classification of the subjects' KC status (kappa = 0.84). CONCLUSION: KC is highly prevalent in Emirati adolescents. Screening secondary school students for keratoconus appears to be feasible and may be indicated in this population to improve early detection and intervention.

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

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

Ocular pain response to treatment in dry eye patients.

PURPOSE: Pain is a frequently reported symptom in dry eye disease (DED). We examine the factors associated with ocular pain severity and patient-reported improvement in ocular pain to commonly used dry eye and pain treatments. METHODS: Cross-sectional study of patients presenting for dry eye management. Demographics, ocular and medical history, OSDI, numeric pain scale, pain descriptors, and subjective response to tried eye drop, systemic, and non-pharmacologic treatments were collected. Statistical analysis was performed to identify differential treatment response in patients with various pain levels using the non-parametric test for trend. RESULTS: 144 patients were categorized into 4 groups according to reported pain severity. Increasing pain was significantly associated with younger age, history of refractive surgery, higher OSDI score, and less likelihood of corneal staining. Patients with higher pain intensity were more likely to report a history of fibromyalgia, depression, anxiety, and migraine. Patients with greater pain severity were less responsive to treatment with artificial tears (p < 0.001), lubricating ointment (p = 0.002), steroid eye drops (p = 0.03), cyclosporine 0.05% (p = 0.03), 20% autologous serum tears (p = 0.01), hot compresses (p = 0.04), lid hygiene (p = 0.002) and punctal occlusion (p = 0.03). CONCLUSIONS: Dry eye patients with severe ocular pain often have associated psychological and systemic pain conditions. Treating the underlying DED is beneficial in reducing ocular pain, however the low rate of a satisfactory response highlights the need for further investigation of effective therapies. Cross-sectional studies can provide guidance in the treatment of patients with dry eye-related ocular pain and guide future prospective studies on potentially effective therapies.

The influence of dissolved organic matter (DOM) on sodium regulation and nitrogenous waste excretion in the zebrafish (Danio rerio).

Dissolved organic matter (DOM) is both ubiquitous and diverse in composition in natural waters, but its effects on the branchial physiology of aquatic organisms have received little attention relative to other variables (e.g. pH, hardness, salinity, alkalinity). Here, we investigated the effects of four chemically distinct DOM isolates (three natural, one commercial, ranging from autochthonous to highly allochthonous, all at ∼6 mg C l(-1)) on the physiology of gill ionoregulation and nitrogenous waste excretion in zebrafish acclimated to either circumneutral (7.0-8.0) or acidic pH (5.0). Overall, lower pH tended to increase net branchial ammonia excretion, net K(+) loss and [(3)H]PEG-4000 clearance rates (indicators of transcellular and paracellular permeability, respectively). However, unidirectional Na(+) efflux, urea excretion and drinking rates were unaffected. DOM sources tended to stimulate unidirectional Na(+) influx rate and exerted subtle effects on the concentration-dependent kinetics of Na(+) uptake, increasing maximum transport capacity. All DOM sources reduced passive Na(+) efflux rates regardless of pH, but exerted negligible effects on nitrogenous waste excretion, drinking rate, net K(+) loss or [(3)H]PEG-4000 clearance, so the mechanism of Na(+) loss reduction remains unclear. Overall, these actions appear beneficial to ionoregulatory homeostasis in zebrafish, and some may be related to physico-chemical properties of the DOM sources. They are very different from those seen in a recent parallel study on Daphnia magna using the same DOM isolates, indicating that DOM actions may be both species and DOM specific.

The effects of fundus photography on the multifocal electroretinogram.

PURPOSE: To determine the effect of flash fundus photography (FFP) on the multifocal electroretinogram (mfERG). METHODS: Ten subjects underwent mfERG testing on three separate dates. Subjects received either mfERG without FFP, mfERG at 5 and 15 min after FFP, or mfERG at 30 and 45 min after FFP on each date. The FFP groups received 10 fundus photographs followed by mfERG testing, first of the right eye then of the left eye 10 min later. Data were averaged and analyzed in six concentric rings at each time point. Average amplitude and implicit times of the N1, P1, and N2 peaks for each concentric ring at each time point after FFP were compared to baseline. RESULTS: Flash fundus photography did not lead to a significant change of amplitude or implicit times of N1, P1, or N2 at 5 min after light exposure. CONCLUSIONS: These findings suggest that it is acceptable to perform mfERG testing without delay after performance of FFP.

Pediatric glaucoma surgery: a report by the American Academy Of Ophthalmology.

OBJECTIVE: To review the current published literature to evaluate the success rates and long-term problems associated with surgery for pediatric glaucoma. METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted in May 2012. The search yielded 838 potentially relevant citations, of which 273 were in non-English languages. The titles and abstracts of these articles were reviewed by the authors, and 364 were selected for possible further review. Members of the Ophthalmic Technology Assessment Committee Glaucoma Panel reviewed the full text of these articles and used the 36 that met inclusion and exclusion criteria for this Ophthalmic Technology Assessment. There were no studies on the topic that provided level I evidence. The assessment included only level II and level III studies. RESULTS: Surgeons treat pediatric glaucoma most commonly with goniotomy, trabeculotomy, trabeculectomy, combined trabeculotomy and trabeculectomy, tube shunt surgery, cyclodestruction, and deep sclerectomy. Certain surgical options seem better for specific diagnoses, such as primary congenital glaucoma, aphakic glaucoma, and glaucomas associated with other ocular or systemic anomalies. CONCLUSIONS: There are many surgical options for the treatment of the pediatric glaucomas. The relative efficacy of these various procedures for particular diagnoses and clinical situations should be weighed against the specific risks associated with the procedures for individual patients.

Retinal blood vessel positional shifts and glaucoma progression.

PURPOSE: To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with ≥8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (<-0.02 decibels [dB]/year), moderate (-0.02 to -0.65 dB/year), or fast (≥-0.65 dB/year) progression. To determine whether graders' assessments of RBV positional shifts were false-positives, a control group consisting of 33 patients with glaucoma with 2 sets of photographs taken on the same day was included. METHODS: Masked graders reviewed serial photographs aligned with automated alternation flicker (EyeIC, Narbeth, PA) and assessed them for the presence of any discrete RBV positional shifts (2 graders) and for traditional measures of structural progression (2 graders), including neuroretinal rim loss, parapapillary atrophy progression, and disc hemorrhage (DH). MAIN OUTCOME MEASURES: Presence or absence of RBV positional shifts, rates of VF progression, and presence or absence of traditional measures of structural progression. RESULTS: A total of 158 image sets (125 longitudinal and 33 same-day controls) from patients with glaucoma were included. Retinal blood vessel shifts were noted in 33 of 125 (26.4%) longitudinally followed glaucomatous eyes and 2 of 33 (6%) same-day control patients (P = 0.01). Agreement between graders I and II was 90.4% (kappa=0.77; P< 0.001). Eyes with RBV positional change progressed more rapidly than those without (-0.55 vs. -0.29 dB/year; 95% confidence interval [CI], 0.03-0.48); P = 0.03). Retinal blood vessel shift was present in 12.1% of minimal progressors versus 31.5% of moderate and fast progressors (P = 0.04). Rate of VF progression was statistically associated with RBV shift (odds ratio [OR], 2.2; 95% CI, 1.1-4.5; P = 0.03). Other variables significantly associated with RBV shift included neuroretinal rim loss (OR, 21.9; 95% CI, 5.7-83.6; P< 0.001) and DH (OR, 4.6; 95% CI, 1.5-15.5; P< 0.01). A multivariable model revealed that rim loss and DH, but not rate of functional change, were significantly associated with RBV shift. CONCLUSIONS: Retinal blood vessel positional shifts occurred in eyes with functionally progressive glaucoma, neuroretinal rim loss, and DH. This is a novel clinical finding that could help identify glaucoma progression or individuals at higher risk for future progression.

Effect of patient positioning on cerebrospinal fluid opening pressure.

BACKGROUND: Prone is the preferred patient position for fluoroscopic-guided lumbar puncture (LP). Normative data for cerebrospinal fluid (CSF) opening pressure (OP) exist for lateral decubitus (LD) positioning only and have not been defined for the prone position. This study compares CSF OP values in the prone and LD positions and examines the effect of body mass index (BMI) on OP. METHODS: Patients undergoing diagnostic or therapeutic fluoroscopic-guided LP were recruited prospectively at 2 tertiary care centers from 2009 to 2012. Following prone fluoroscopic-guided LP, patients were rolled to the LD position for repeat CSF OP measurement. In addition to comparing the mean OP in each position, the relationships between OP, body position, and BMI were also explored. RESULTS: Fifty-two patients were enrolled. A mean OP difference of 1.2 cm H2O was observed (prone: 26.5 cm H2O; LD: 27.7 cm H2O; P = 0.07). No correlation between CSF OP and BMI was seen in either position. CONCLUSIONS: No statistically or clinically significant difference between prone and LD OP was identified. BMI does not appear to affect CSF OP measurement in either position.

Evaluation of the anterior chamber angle in glaucoma: a report by the american academy of ophthalmology.

OBJECTIVE: To assess the published literature pertaining to the association between anterior segment imaging and gonioscopy and to determine whether such imaging aids in the diagnosis of primary angle closure (PAC). METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted on July 6, 2011. The searches yielded 371 unique citations. Members of the Ophthalmic Technology Assessment Committee Glaucoma Panel reviewed the titles and abstracts of these articles and selected 134 of possible clinical significance for further review. The panel reviewed the full text of these articles and identified 79 studies meeting the inclusion criteria, for which the panel methodologist assigned a level of evidence based on a standardized grading scheme adopted by the American Academy of Ophthalmology. Three, 70, and 6 studies were rated as providing level I, II, and III evidence, respectively. RESULTS: Quantitative and qualitative parameters defined from ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (OCT), Scheimpflug photography, and the scanning peripheral anterior chamber depth analyzer (SPAC) demonstrate a strong association with the results of gonioscopy. There is substantial variability in the type of information obtained from each imaging method. Imaging of structures posterior to the iris is possible only with UBM. Direct imaging of the anterior chamber angle (ACA) is possible using UBM and OCT. The ability to acquire OCT images in a completely dark environment allows greater sensitivity in detecting eyes with appositional angle closure. Noncontact imaging using OCT, Scheimpflug photography, or SPAC makes these methods more attractive for large-scale PAC screening than contact imaging using UBM. CONCLUSIONS: Although there is evidence suggesting that anterior segment imaging provides useful information in the evaluation of PAC, none of these imaging methods provides sufficient information about the ACA anatomy to be considered a substitute for gonioscopy. Longitudinal studies are needed to validate the diagnostic significance of the parameters measured by these instruments for prospectively identifying individuals at risk for PAC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Double peeling during vitrectomy for macular pucker: the Charles L. Schepens Lecture.

Epiretinal membranes are commonly encountered in retinal practice, and they result in decreased vision. The present work addresses whether peeling of the internal limiting membrane is necessary during vitrectomy for macular pucker. We performed a retrospective analysis to investigate the effects of "single peeling," in which only the epiretinal membrane was peeled, and "double peeling," in which the internal limiting membrane was also stained and peeled. Although significantly more patients in the single-peeling group had an epiretinal membrane remaining in the central fovea postoperatively, visual acuity was not found to differ between the 2 groups in the short term. Patients who had an epiretinal membrane for more than 18 months had significantly worse visual acuity outcomes. Unexpectedly, there was a greater proportional decrease in central macular thickness in the single-peeling group than in the double peeling group, a finding that deserves further study.

Bcl-2 overexpression ameliorates immune complex-mediated arthritis by altering FcγRIIb expression and monocyte homeostasis.

RA is a chronic autoimmune disease characterized by accumulation of inflammatory cells within synovial joints. RA is associated with a failure of apoptosis of infiltrating leukocytes, thought to be a result of overexpression of prosurvival Bcl-2 proteins. Overexpression of Bcl-2 in hematopoietic cells can result in spontaneous autoimmunity. We therefore hypothesized that increased Bcl-2 in the hematopoietic compartment would reduce apoptosis and thereby, exacerbate inflammatory arthritis. Paradoxically, we found that overexpression of Bcl-2 in mice (vav-bcl-2) markedly reduced pathology in antibody-dependent models of RA (CIA and K/BxN serum transfer arthritis). No such protection was observed in a model of CD4(+) T cell-dependent, B cell-independent arthritis (mBSA/IL-1-induced arthritis). In CIA, vav-bcl-2 Tg mice had lower antibody production to CII, which might explain reduced disease. However, Bcl-2 overexpression also reduced passive K/BxN serum transfer arthritis. Overexpression of Bcl-2 caused a monocytosis, with preferential expansion of Ly6C(lo) monocytes and increased expression of the inhibitory receptor for IgG, FcγRIIb, on leukocytes. Skewing of the myeloid cell population, increases in FcγRIIb, and reduced arthritis were independent of the hypergammaglobulinemia found in vav-bcl-2 Tg mice. These data reveal selective effects of the Bcl-2-regulated apoptotic pathway on monocyte differentiation and the expression of FcRs critical for regulation of antibody/immune complex-mediated disease.

Exploring patient perceptions of PSA screening for prostate cancer: risks, effectiveness, and importance.

OBJECTIVE: To study the beliefs of a group of Canadian men regarding the risks, effectiveness, and importance of routine prostate-specific antigen (PSA) testing when used as a screening tool for prostate cancer. DESIGN: A 1-page questionnaire designed to gauge patient beliefs about PSA screening. SETTING: Two primary care clinics in Kingston, Ont. PARTICIPANTS: Seventy-two men aged 41 to 80. MAIN OUTCOME MEASURES: Whether men believed that the PSA blood test was not risky when used as a screening test for prostate cancer, was effective at preventing death from prostate cancer, and was important for their health. RESULTS: Fifteen men reported having visited their physicians because of difficulty urinating in the past 2 years, or a personal history of prostate cancer, and were excluded; for these men, the use of the PSA blood test would not be for screening. Of the 57 men considered in the study, 54 (95%) believed that using the PSA blood test as a screening tool for prostate cancer was not risky, 39 (68%) believed that the PSA blood test was good or very good at preventing death from prostate cancer, and 45 (79%) believed that the routine use of the PSA blood test was important or very important for their health. Men in the suggested screening age group of 51 to 70 years (n = 32) had an equally positive impression of PSA screening. CONCLUSION: Despite a limited body of evidence showing its effectiveness, Canadian men continue to have a favourable impression of PSA screening and remain largely unaware of potential adverse events associated with PSA testing.