Fingolimod-associated macular edema controlled with nepafenac non-steroidal anti-inflammatory opthalmologic applications.

BACKGROUND: Fingolimod, an immunomodulatory agent, is used for the treatment of relapsing-remitting multiple sclerosis (RRMS). Fingolimod-associated macular edema (FAME) is a known complication with an incidence of 0.4%. The current recommendation for treatment of FAME is cessation of fingolimod. There are few case reports with management of FAME with steroid eye drops. CASE PRESENTATION: A 38-year-old Caucasian female patient with history of relapsing-remitting multiple sclerosis (RRMS) and treated with fingolimod developed Fingolimod-associated macular edema (FAME). Nevertheless, FAME was successfully treated with nonsteroidal anti-inflammatory eye drops without discontinuation of fingolimod. CONCLUSION: FAME may be managed with non-steroidal eye drops without discontinuation of fingolimod in appropriate patient monitored with close follow up.

PREDICTIVE FACTORS FOR PROLIFERATIVE VITREORETINOPATHY FORMATION AFTER UNCOMPLICATED PRIMARY RETINAL DETACHMENT REPAIR.

PURPOSE: To determine predictive factors of proliferative vitreoretinopathy (PVR) formation after uncomplicated primary retinal detachment repair. METHODS: Retrospective, single-center, case-control study of 74 consecutive patients with (37 eyes) and without (37 eyes) PVR formation after undergoing uncomplicated primary surgery for retinal detachment repair. Logistic regression was used to assess factors associated with PVR formation. RESULTS: Retinal detachment involving the macula was 4.2 times (adjusted odds ratio; 95% confidence interval, 1.4-12.9; P = 0.0119) more likely to have PVR formation compared with those without. Patients who were current or former smokers were 3.6 times (adjusted odds ratio; 95% confidence interval, 1.1-11.7; P = 0.0352) more likely to have PVR formation compared with nonsmokers. Compared with 25-gauge (g) vitrectomy, larger gauge vitrectomy (20 g or 23 g) was 3.6 times (adjusted odds ratio; 95% confidence interval, 1.2-11.3; P = 0.0276) more likely to have PVR formation. Duration of retinal detachment symptoms, high myopia, lens status, lattice degeneration, location of retinal break, number of retinal breaks, and surgical technique (e.g., scleral buckle with or without vitrectomy versus vitrectomy alone) were not found to be predictive of PVR formation. CONCLUSION: Cigarette smoking and macular involvement are significant risk factors predictive of PVR formation after uncomplicated primary retinal detachment repair.

Endophthalmitis after Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors: Management and Visual Outcomes.

PURPOSE: We describe the presentation of patients developing endophthalmitis after intravitreal injection with vascular endothelial growth factor (VEGF) inhibitors. Moreover, we evaluate the management by comparing the outcomes of immediate tap and injection of intravitreal antibiotics (TAI) versus initial surgical pars plana vitrectomy (PPV). Finally, we analyze the predictive factors of visual outcomes at 6-month follow-up. DESIGN: Retrospective, single-center, nonrandomized interventional study. PARTICIPANTS: Patients developing endophthalmitis after receiving an intravitreal injection of anti-VEGF agent between 2006 and 2016. METHODS: All patients received a vitreous biopsy sent for cultures before the initiation of treatment: TAI group versus PPV with intravitreal antibiotics (PPV group). MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at 6-month follow-up after treatment for endophthalmitis. RESULTS: A total of 258 357 intravitreal injections occurred over the course of the 10-year period, of which 40 patients (0.016%) had endophthalmitis within 3 weeks after injection. In total, 34 patients (85.0%) had pain and 25 patients (62.5%) had hypopyon on initial examination. Among 24 culture-positive cases, 66.7% of the causative organisms were coagulase-negative Staphylococcus, followed by Streptococcus species (10.0%). The best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution [logMAR]) at 6-month follow-up was significantly worse for patients who had a positive culture for Streptococcus species (4.0; standard deviation [SD], 0.8) (approximately light perception) compared with those who had a positive culture for coagulase-negative Staphylococcus (0.4; SD, 0.3) (∼20/50) (P < 0.0001). Compared with the TAI group, a higher proportion of samples were culture-positive in the PPV group (90.9% vs. 48.3%, P = 0.03). There was no statistically significant difference in BCVA at 6-month follow-up between the TAI and PPV groups. Younger age (<85 years) and lower intraocular pressure (IOP) (≤25 mmHg) at presentation were predictive of achieving a BCVA of 20/400 or better at 6-month follow-up after treatment. Initial management (TAI vs. PPV), duration of symptoms, presence of pain, presence of hypopyon, presenting BCVA, and culture status (positive vs. negative) were not found to be predictive of visual outcomes at 6-month follow-up. CONCLUSIONS: No significant difference in BCVA at 6-month follow-up was detected between the TAI and PPV groups. Younger age and lower IOP at presentation were associated with better visual outcomes at 6-month follow-up.

The role of G-protein receptor 84 in experimental neuropathic pain.

G-protein receptor 84 (GPR84) is an orphan receptor that is induced markedly in monocytes/macrophages and microglia during inflammation, but its pathophysiological function is unknown. Here, we investigate the role of GPR84 in a murine model of traumatic nerve injury. Naive GPR84 knock-out (KO) mice exhibited normal behavioral responses to acute noxious stimuli, but subsequent to partial sciatic nerve ligation (PNL), KOs did not develop mechanical or thermal hypersensitivity, in contrast to wild-type (WT) littermates. Nerve injury increased ionized calcium binding adapter molecule 1 (Iba1) and phosphorylated p38 MAPK immunoreactivity in the dorsal horn and Iba1 and cluster of differentiation 45 expression in the sciatic nerve, with no difference between genotypes. PCR array analysis revealed that Gpr84 expression was upregulated in the spinal cord and sciatic nerve of WT mice. In addition, the expression of arginase-1, a marker for anti-inflammatory macrophages, was upregulated in KO sciatic nerve. Based on this evidence, we investigated whether peripheral macrophages behave differently in the absence of GPR84. We found that lipopolysaccharide-stimulated KO macrophages exhibited attenuated expression of several proinflammatory mediators, including IL-1ß, IL-6, and TNF-α. Forskolin-stimulated KO macrophages also showed greater cAMP induction, a second messenger associated with immunosuppression. In summary, our results demonstrate that GPR84 is a proinflammatory receptor that contributes to nociceptive signaling via the modulation of macrophages, whereas in its absence the response of these cells to an inflammatory insult is impaired.

Paraneoplastic sarcoid-like reactions and the eye.

BACKGROUND: Sarcoid-like reactions have been reported and confirmed by histopathology in patients with malignant disease. This series demonstrates the complex relationship of malignancy and sarcoidosis as pertaining to the eye, which, to the best of our knowledge, has not been previously reported in the literature. METHODS: Retrospective case study of five patients with sarcoid-like reactions. Patients 1 to 4 represent patients with ocular sarcoid-like reaction and systemic malignant disease. Patient 5 had ocular malignancy and systemic sarcoid-like reaction; workup revealed renal cell cancer. For each patient, other etiologies of nonnecrotizing granulomatous inflammation were excluded. RESULTS: Sarcoid-like reactions have been described in the literature when nonnecrotizing granulomas occur in association with malignancy and in the absence of multiorgan involvement as seen with systemic sarcoid. In our series, sarcoid-like reactions involved the vitreous in three patients, retina in one patient, and the choroid and lung in one patient. Sarcoid-like reaction preceded the diagnosis of malignancy in two patients, was found concomitantly with malignancy in one patient, and followed malignancy in two patients. Two patients had hematologic malignancy, one patient had endometrial carcinoma, one had renal cell carcinoma, and one patient had both renal cell carcinoma and uveal melanoma. Four patients had findings of nonnecrotizing granulomas confirmed by histopathology. CONCLUSION: Sarcoid-like reactions can occur in the eye, and ocular malignancies may incite sarcoid-like reaction. Ocular sarcoid-like reactions have paraneoplastic features in that they can occur at a site distant from malignancy and may precede, occur simultaneously with, or follow malignancy.

In verbis, vinum? Relating themes in an open-ended writing task to alcohol behaviors.

Alcohol's function as a regulator of emotions has long been denoted in figures of speech, most famously 'in vino, veritas' (in wine, truth). In contrast, we ask whether an individual's self-reported alcohol consumption and related attitudes can be correlated with the words they use to write about alcohol. Participants completed an open-ended essay as part of a survey on alcohol attitudes and behaviors. We used a computerized technique, the Meaning Extraction Method, to summarize the responses into thematic tropes, and correlated these with quantitative measurements of demographics, attitudes and behaviors. Participants were recruited using a random population postal survey in the UK (n=1001). Principal components analysis identified regular co-occurring words, to locate themes in the responses. Seven themes were identified that corresponded to both negative and positive aspects of alcohol consumption ranging from concern for the influence of alcohol on others (e.g., children and family) to participants' own enjoyment of alcohol (e.g., social drinking). Small but significant correlations suggested a relationship between the essay responses and individual consumption patterns and attitudes.

Primary ocular toxoplasmosis secondary to venison consumption.

Purpose: To describe primary ocular toxoplasmosis infection related to ingestion of undercooked venison. Observations: This single site, retrospective case series reviewed 4 patients with primary ocular toxoplasmosis that was acquired by ingesting undercooked venison. De-identified data was collected regarding baseline patient characteristics including age, sex, past medical and ocular history, onset of symptoms, visual acuity (VA), response to treatment, and workup. All patients with acquired toxoplasmosis had similar chronology of systemic and ocular symptoms. Exposure occurred in October or November and systemic symptoms developed within 2 weeks, followed by ocular symptoms an average of 2.6 months later. Average age at onset was 56 ± 13 (age ± SD) years old and all were male. Average initial and final VA were 20/50 and 20/50, respectively. Positive anti-toxoplasma IgM and IgG serologies were found in all cases. All patients were treated with trimethoprim/sulfamethoxazole and achieved rapid improvement. Complications occurred in 50% of cases and included epiretinal membrane, cystoid macular edema, vitreoretinal traction, and neovascularization. Conclusions and importance: Consumption of undercooked venison is a source of primary ocular toxoplasmosis even in immunocompetent hosts and has a clear chronology. A presentation of retinochoroiditis during the winter months should prompt questioning for exposure to wild game.

Planned and unplanned discharge from alcohol services in Scotland, 2004-2008.

AIMS: Available data suggests that the rate of unplanned discharge from alcohol treatment services is an international problem reflective, perhaps, of ambivalence surrounding treatment in general. Given Scotland's escalating prevalence of alcohol misuse, a preliminary study of Scottish dropout rates would make a useful contribution to the international scene. METHODS: A retrospective analysis of discharge statuses (planned/unplanned/disciplinary) of entries to alcohol treatment services between 1 April 2004 and 31 March 2008 was conducted on data provided by 10 regional Drug and Alcohol Action Teams (DAATs) and three individual treatment providers. RESULTS: Of 48,299 cases, 52.23% (n = 25,231) were unplanned discharges. Data showed a general increasing trend in the rate of planned discharges across the examined 4-year period, from 41.66% in 2004-2005 to 51.94% in 2007-2008. Inspection of the data revealed marked regional variations in ratios of planned to unplanned discharge, with only four of the 10 regions examined reporting a planned discharge rate >50%. CONCLUSION: More than one of every two entries to alcohol misuse services between 2004 and 2008 resulted in an unplanned discharge. The trend of improvement over the examined 4-year period was not consistent for all regions. A comparison of this figure with available US and Welsh data is made. The importance of these data in assessing the cost-effectiveness of alcohol treatment services and implications for policy making is discussed.

Isolated cilioretinal artery occlusion secondary to perinuclear antineutrophil cytoplasmic antibody vasculitis.

INTRODUCTION: Antineutrophil cytoplasm antibody-associated vasculitides encompass a diverse spectrum of autoimmune diseases characterized by necrotizing small vessel vasculitis. Ocular manifestations may be the presenting findings of antineutrophil cytoplasm antibody-associated vasculitides. METHODS: Single, retrospective case study. RESULTS: We report the rare case of a 55-year-old woman with a cilioretinal artery occlusion as the presenting feature of perinuclear antineutrophil cytoplasm antibody-associated microscopic polyangiitis. CONCLUSIONS: Although rare, antineutrophil cytoplasm antibody-related vasculitis should be considered in any retinal vascular occlusion, particularly in the setting of patients with new vague headaches and a paucity of vasculopathic risk factors.

Public health or social impacts? A qualitative analysis of attitudes toward the smoke-free legislation in Scotland.

INTRODUCTION: Introduction of smoke-free legislation presents a unique opportunity to study how population-level interventions can challenge existing smoking norms. Our study examined support and opposition to the Scottish legislation and ascertained the relative importance of social and health factors in shaping attitudes among bar customers. METHODS: Repeat (pre-/post-legislation) recorded and transcribed semistructured interviews with customers (n = 67/62) of eight community bars in contrasting settings were conducted, and data were analyzed thematically. RESULTS: While the legislation was marketed primarily in terms of gains to public and individual health, supportive and opposing responses to the legislation tended to be framed around libertarian and practical factors. Attitudes tended to be stable across both waves of data collection. DISCUSSION: It is concluded that reasons for smoking were not challenged by promotion of the legislation. In addition to a focus on health gains, social marketing of smoke-free legislation and initiatives may therefore benefit from a stronger focus on social and contextual effects of such policies.

Ocular manifestations of systemic lupus erythematosus.

PURPOSE OF REVIEW: To describe the ophthalmic manifestations of systemic lupus erythematosus and to review recent advances in our understanding of the pathogenesis and treatment of this condition. RECENT FINDINGS: Significant vision loss and associated ocular morbidity are possible in systemic lupus erythematosus, particularly in cases of retinal or central nervous system involvement. Considerable progress has been made in our understanding of the immunologic mechanisms of disease. Approaches to treatment include the use of systemic immunosuppressive medications. Biologic agents are being developed to target specific aspects of the immune response. SUMMARY: Ocular involvement is not uncommon in systemic lupus erythematosus. Aggressive systemic therapy is often needed to control the disease. Several new immunomodulatory treatment strategies are being developed which may show great promise in the future.

Successful delayed surgical revision of a dislocated LASIK flap.

A 53-year-old woman presented with decreased vision and light sensitivity in the left eye for 3 months' duration. The patient had injured her left eye 7 months after laser in situ keratomileusis (LASIK), causing a traumatic flap dislocation that had not been repositioned. Three months after the injury, the LASIK flap was successfully repositioned with extensive intraoperative epithelial debridement and the use of flap sutures. Uncorrected visual acuity improved from 20/200 and J12 preoperatively to 20/60 and J1 postoperatively. This case illustrates that, although immediate flap repositioning is always recommended, a dislocated LASIK flap can be successfully repositioned even months after the trauma with an excellent visual outcome.

Late-onset bleb-associated endophthalmitis and continuous positive airway pressure.

PURPOSE: To raise awareness of a possible association between continuous positive airway pressure (CPAP) devices and postoperative bleb-related infection. OBSERVATIONS: A 57-year old patient on CPAP presented with unilateral bleb-associated endophthalmitis 32 months after routine ExPress Trabeculectomy with mitomycin C. The offending organism, Streptococcus mitis, is a nonmotile and generally non-virulent pathogen which predominates in the normal human respiratory flora. CONCLUSIONS AND IMPORTANCE: This conceptual report underscores a potential relationship between CPAP use and bleb-associated endophthalmitis. Streptococcal species are the most commonly reported causative organisms in bleb-associated endophthalmitis, and S. mitis is of particular concern as the most abundant microbe among all human oral flora. A logical risk factor for infection, the CPAP device may inadvertently deliver such organisms to the vulnerable conjunctival filtering bleb.

Contribution of migrant coffee labourers infected with Onchocerca volvulus to the maintenance of the microfilarial reservoir in an ivermectin-treated area of Mexico.

BACKGROUND: Since 1991, in Mexico, ivermectin has been administered twice a year to all residents in the onchocerciasis endemic foci which are mainly located in the coffee growing areas. However, the presence of a potentially infected itinerant seasonal labour force which is not treated regularly could jeopardise the attainment of the 85% coverage which is the present target for elimination of the disease. METHODS: The prevalence and intensity of Onchocerca volvulus microfilariae (mf), as well as their transmission from humans to vectors, were assessed during the coffee planting-clearing and harvesting seasons of 1997-1998, and 1998-1999 in two localities (I and II) of Southern Chiapas, Mexico, which regularly receive an influx of untreated migrant coffee labourers. RESULTS: Localities I and II had, respectively, an average of 391 (+/- 32) and 358 (+/- 14) resident inhabitants, and 70 (+/- 52) and 498 (+/- 289) temporary labourers. The ratio of migrants to residents ranged from 0.1:1 in locality I to 2.4:1 in locality II. The proportion of infected Simulium ochraceum s.l. parous flies was significantly lower in locality I than in locality II, and significantly higher during the stay of the migrants than before their arrival or after their departure. Parity and infection were higher in May-July than in November-February (in contrast with the latter being typically considered as the peak onchocerciasis transmission season by S. ochraceum s.l.). CONCLUSION: The presence of significant numbers of untreated and potentially infected migrants may contribute to ongoing transmission, and their incorporation into ivermectin programmes should be beneficial for the attainment of the elimination goals of the regional initiative. However, the possibility that the results also reflect transmission patterns for the area cannot be excluded and these should be analyzed further.

Retinal Injury Secondary to Laser Pointers in Pediatric Patients.

This case report describes 4 male children (age, 9-16) who had laser-related retinal injury to the macula of 1 eye or both eyes due to the mishandling of the laser pointer devices at a single vitreoretinal clinical practice. The presenting symptoms associated with laser pointer injury include central vision loss, central scotoma, and metamorphopsia. Clinical findings of laser-related retinal injury include reduced visual acuity, disruption of the photoreceptor ellipsoid zone, retinal pigment epithelium atrophy, and choroidal neovascular membrane formation. Disruption of the foveal ellipsoid zone (photoreceptor inner segment/outer segment layer) is the most common finding on optical coherence tomography imaging. Three patients had potential irreversible vision loss. Laser pointers are readily available and appropriate use of laser pointers in the pediatric population must be emphasized due to the potential irreversible retinal injury. Health professionals, school teachers, and parents should raise public awareness of this emerging public health issue by educating children about the dangers of laser pointers. Laser pointer devices among children should be discouraged and limited due to the possibility of permanent harm to themselves and others. Legislation and laws may be required to better control the sale and use of these devices.

Variability in lay perceptions of depression: a vignette study.

This paper describes a study investigating lay perceptions of depression in terms of perceived severity. Students (N = 128) were presented with vignettes describing individuals with symptoms of depression based on DSM-IV. The descriptions were varied in terms of gender, social status, and a self-referent manner of communicating depressive symptomatology. Participants were asked to rate the degree to which vignette characters were thought to be depressed on a Likert-type scale. Results indicate that a non-self-referent style of communicating depressive symptoms by female vignette characters was seen as an indication of elevated levels of depression, and these findings are discussed with reference to the literature.

Delivery of several forms of DNA, DNA-RNA hybrids, and dyes across human sclera by electrical fields.

PURPOSE: Iontophoresis has been used for drug delivery across the cornea for many years. We sought to test whether small charged dyes and DNA can be transferred across human sclera by an electric field. METHODS: Full-thickness human scleral fragments were embedded vertically in an agarose gel and positioned to completely span individual gel lanes. The scleral fragments were located approximately 1 cm downstream from the gel wells. DNA or dyes were loaded into the wells and electrophoresis was carried out at about 3.3 V/cm for approximately 2 h per run. Movement of DNA and dyes through the agarose and sclera was measured with either digital time-lapse photography or through DNA extraction and purification from the gel. SYBR green stain was used as a sensitive method to detect DNA. RESULTS: Digital time-lapse photography of agarose gel electrophoresis revealed that two dyes, xylene cyanol and bromphenol blue, passed through the sclera in the presence of an electric field. Xylene cyanol was driven through the sclera virtually unimpeded except for some spreading of the dye. Bromphenol blue was slowed markedly by the sclera, but it too eventually passed through the tissue. Small DNAs, including a single stranded 51-mer and a double hairpin 68-mer oligonucleotide, passed through the sclera as detected by SYBR green staining. Linear double stranded DNAs ranging from 50 bp to 12,000 bp passed through the sclera. The larger the DNA, the slower the rate of passage through the sclera, and the greater the band spreading. pEGFP-1 (a 3 kb plasmid) passed through the sclera but was accompanied by a great amount of band spreading. Following completion of the initial electrophoresis run, the plasmid DNA was extracted from the smeared bands in the agarose distal to the sclera and re-run on a second gel without sclera. The initially smeared plasmid bands resolved into 2 distinct bands after extraction and purification and matched well with control plasmid bands. CONCLUSIONS: Charged molecules such as xylene cyanol, bromphenol blue, and DNAs ranging from 51 bp oligonucleotides to a 3 kb plasmid can be driven across human sclera by an electric field and directly detected. Passage of plasmids was efficient, but the plasmid bands were diffuse after transit. This technique offers promise as a noninvasive DNA delivery tool, where gene therapy can be accomplished by small RNA or DNA synthetic oligonucleotides, larger double stranded fragments, or even plasmids.