The risk for ophthalmological conditions in ulcerative colitis: A population-based case-control study. Is silica dust-exposure associated with inflammatory eye disease?

PURPOSE: To study the risk for eye diseases in individuals with Ulcerative Colitis (UC), and to assess whether silica dust-exposure could contribute to the development of inflammatory eye diseases. METHODS: A case-control study was conducted using a patient register processed by the National Board of Health and Welfare (NBHW) and Statistics Sweden. Cases were diagnosed with UC between 2007 and 2016. Matching was done with two random controls having the same age, sex and county of residence, without a systemic inflammatory disease. Using a job-exposure matrix, cases and controls were assessed for work-related silica dust exposure. The risk for eye disease was estimated by Cox regression analysis with calculation of Hazard Ratio (HR). RESULTS: A total of 58 989 individuals were included, comprising 19 663 cases and 39 326 controls. The sex distribution was similar. Overall, individuals with UC had an increased risk for eye disease, specified in ICD 10 chapter VII (H00-H59) with HR 1.25 (CI 1.20-1.32). The highest HR on block-level for cases was 1.52 (CI 1.36-1.70), (H15-H22), which includes episcleritis, keratitis and anterior uveitis. The risk for ocular disease was higher in silica dust-exposed than non-exposed with a HR of 1.44 (CI 1.16-1.78) and 1.25 (CI 1.19-1.31), respectively. Among cases, the risk for iridocyclitis (H20) was further elevated by silica dust exposure, with HR of 3.84 (CI 1.64-8.97) in exposed compared to 1.94 (1.57-2.41) in non-exposed. CONCLUSION: UC is associated with an increased risk for eye diseases, including inflammatory conditions. Our findings highlight that silica dust-exposure may be of importance in the pathogenesis of uveitis.

The level of education and the risk for retinal detachments and breaks: A registry-based case-control study.

PURPOSE: Myopia is the most important risk factor for developing retinal tears and retinal detachment (RD). Due to altered lifestyle factors myopia is increasing in the world. In this study, the correlation between educational level and risk for retinal detachment were analysed. METHODS: A case-control registry study was conducted including a total of 10 268 individuals. Data were collected from registries of the Swedish National Board of Health and Welfare as well as the Swedish Central Bureau of Statistics. Cases were defined as ICD-10 H33 (retinal detachments and breaks). For each case, a matched control was selected with the same age and sex, living in the same county at the time of diagnosis. The study population was divided into seven groups with regard to educational level and compared using conditional logistic regression. RESULTS: In the total population, the odds ratio (OR) increased in a proportional fashion with a higher level of education. The odds ratio for the total population at the highest education level was 1.77 and increased to 2.00 when excluding individuals with diabetes. Out of the 5134 cases, 72% were men and 28% women. A statistically significant difference between sexes was only confirmed for the second highest education level. CONCLUSION: Individuals with a longer education have a significantly higher risk for retinal complications in the form of RD and breaks. Higher education is a risk factor for retinal complications in both sexes but seemingly more strongly in men.

Carpal Tunnel Syndrome and Hand-Arm Vibration: A Swedish National Registry Case-Control Study.

OBJECTIVE: To investigate the increased risk for carpal tunnel syndrome (CTS) in men and women with hand-arm vibration (HAV) exposure. DESIGN: Case-control study of CTS where 4396 cases was obtained from National Outpatient Register between 2005 through 2016. Cases were matched to controls and exposure was estimated using a job exposure matrix. RESULTS: Exposure to HAV increased the risk of CTS with an OR of 1.61 (95% CI 1.46-1.77). The risk was highest in men <30 years of age and among women <30 years no increased risk was observed. The risk increased with a mean year exposure above 2.5 m/s2 to OR 1.84 (95% CI 1.38-2.46). CONCLUSIONS: HAV exposure increase the risk of CTS in both genders, with highest risk increase in younger men. This emphasize identification of HAV exposure in patients with CTS.

Arterial abnormalities in the hands of workers with vibration white fingers - a magnetic resonance angiography case series.

Vibration white finger (VWF) is a complication from exposure to hand-arm vibrations. Poor knowledge of the pathophysiology of VWF means that making an accurate prognosis is difficult. Thus, a better understanding of VWF's pathophysiology is of importance.The purpose of this study was to investigate whether there were arterial abnormalities in the hands in patients with VWF and a positive Allen's test, using ultrasound and MRA imaging.This was a case series where arterial abnormalities in the hands were investigated in ten participants with VWF and using prolonged Allen's test (> 5 s). The participants had an average vibration exposure of 22 years and underwent Doppler ultrasound and Magnetic Resonance Angiography (MRA) to check for arterial abnormalities.The participants had VWF classified as 1-3 on the Stockholm workshop scale. Ultrasound and MRA identified vascular abnormalities in all participants, the predominant finding was missing or incomplete superficial arch. Also, stenosis was identified in four participants.This study reveals a high proportion of arterial stenosis and abnormalities in patients with VWF and a prolonged Allen's test.

A prospective long-term follow-up study of optic disc pit maculopathy treated with pars plana vitrectomy, drainage of subretinal fluid and peeling of internal limiting membrane.

PURPOSE: To describe the long-term results of surgical repair of patients with optic disc pit maculopathy (ODP-M). METHODS: Prospective, consecutive, noncomparative follow-up study including 12 patients with ODP-M treated by pars plana vitrectomy (PPV), peeling of internal limiting membrane followed by gas tamponade. Subretinal fluid (SRF) was drained in 11 eyes through a retinotomy without laser photocoagulation. Preoperatively, macular detachment with retinoschisis was seen in 9 out of 12 eyes with three eyes having only subretinal fluid in the macular area. The median age at surgery was 20 years (range 9-60 years). RESULTS: Follow-up time from initial surgery was 63 months (median). Eight eyes were anatomically reattached after one operation without remaining SRF in the macula. Two patients required a reoperation due to leakage from the retinotomy and another two underwent a second PPV procedure due to late recurrences. Successful healing was at follow-up control observed in 11 of 12 eyes. There was no statistically significant difference in visual acuity between patients before and after surgery (p = 0.24). Central visual field defects with depressed mean deviation were detected in all treated eyes. CONCLUSION: In this long-term study of ODP-M final outcome regarding healing was relatively efficacious, however, a relatively large proportion had complications associated to retinotomies. We conclude that drainage of SRF should likely be avoided since it appears to contribute little to the resorption rate of SRF and seems to linked to unnecessary risks.

Different photodynamic effects of blue light with and without riboflavin on methicillin-resistant Staphylococcus aureus (MRSA) and human keratinocytes in vitro.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of infections in humans. Photodynamic therapy using blue light (450 nm) could possibly be used to reduce MRSA on different human tissue surfaces without killing the human cells. It could be less harmful than 300-400 nm light or common disinfectants. We applied blue light ± riboflavin (RF) to MRSA and keratinocytes, in an in vitro liquid layer model, and compared the effect to elimination using common disinfection fluids. MRSA dilutions (8 × 105/mL) in wells were exposed to blue light (450 nm) ± RF at four separate doses (15, 30, 56, and 84 J/cm2). Treated samples were cultivated on blood agar plates and the colony forming units (CFU) determined. Adherent human cells were cultivated (1 × 104/mL) and treated in the same way. The cell activity was then measured by Cell Titer Blue assay after 24- and 48-h growth. The tested disinfectants were chlorhexidine and hydrogen peroxide. Blue light alone (84 J/cm2) eliminated 70% of MRSA. This dose and riboflavin eradicated 99-100% of MRSA. Keratinocytes were not affected by blue light alone at any dose. A dose of 30 J/cm2 in riboflavin solution inactivated keratinocytes completely. Disinfectants inactivated all cells. Blue light alone at 450 nm can eliminate MRSA without inactivation of human keratinocytes. Hence, a high dose of blue light could perhaps be used to treat bacterial infections without loss of human skin cells. Photodynamic therapy using riboflavin and blue light should be explored further as it may perhaps be possible to exploit in treatment of skin diseases associated with keratinocyte hyperproliferation.

An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease.

Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs. Currently, no standard treatment is available, but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs*1395), was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium (RPE). The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD.

[Floorball ­ a common cause of sport related eye injury]. / Innebandy är en vanlig orsak till sportrelaterade ögonskador - Skyddsglasögon bör användas vid innebandyspel på alla nivåer.

Floorball - a common cause of sport related eye injury The aim of this study was to survey the incidence and type of sport related to eye injuries with special interest in floorball. A prospective study was conducted December 1st 2013 through November 30th 2014 at the Department of Ophthalmology, Örebro University Hospital. All patients presenting with an acute sports related eye injury were offered to be included. Information was collected from a self-administered questionnaire and from medical journals. During the study period, 49 patients sought care for sports related eye injuries, and 26 (53%) of those were related to floorball. The number of patients who agreed to take part in the study was 38, of which 25 had injuries related to floorball. Among the floorball players, there were two patients where the injury caused permanent vision impairment. None of the floorball players wore eye protection at the time of injury. According to this study, protective eyewear should be recommended when playing floorball, regardless of age or setting.

Levels of beta-trace protein in optic disc pit with macular detachment.

BACKGROUND: To report beta-trace protein (ßTP) levels in the subretinal fluid (SRF) of four patients with a macular detachment associated with optic disc pit (ODP). METHODS: Four patients with a serous retinal detachment involving the macula was operated by pars plana vitrectomy (PPV) with C2 F6 gas tamponade and peeling of internal limiting membrane (ILM). Patients with a follow-up period exceeding one year postoperatively were included in the study. The SRF was drained using a fine cannula without laser photocoagulation, and the samples were analysed using particle-enhancing nephelometry. The levels of ßTP were compared to 20 routine cerebrospinal fluid (CSF) samples. RESULTS: In four of the five samples from SRF had relatively low ßTP levels, with a mean concentration of 6.6 mg/l (range 2.0 to 23.1 mg/l) compared to 16.0 mg/l (range 6.3-26.8 mg/l) in CSF. The only SRF sample within the range corresponding to normal CSF was the first sample from patient 4, and the analysis of the renewed aspirate during the second operation was 2.8 mg/l. Postoperatively, the regression of SRF was slow, but regression of SRF in the foveal region took place in all cases; however, visual acuity (VA) was improved in only half of the patients. CONCLUSION: The results from the analysed SRF regarding ßTP concentration in these patients indicate that the SRF in ODP is not identical to CSF, as the concentrations of ßTP differ.

Photochemical eradication of methicillin-resistant Staphylococcus aureus by blue light activation of riboflavin.

PURPOSE: To compare elimination of methicillin-resistant Staphylococcus aureus (MRSA) by exposure of blue light alone and with riboflavin. METHODS: A reference strain of MRSA was cultured and diluted in PBS with and without riboflavin (0.01%). Fifteen microlitre was added on a microscope slide, creating a fluid layer with a thickness of around 400 microns. Both of the bacterial suspensions were exposed to blue light, and the effect between exposure with and without riboflavin was compared. Evaluation involved two different wavelengths (412 and 450 nm) of blue light with a lower (5.4 J/cm2 ) and higher dose (approximately 28.5 J/cm2 ). The effect of 412 nm light was also evaluated for a thicker fluid layer (1.17 mm). After exposure, colony-forming units (CFUs) were determined for each solution. All measurements were repeated eight times. RESULTS: The reductions in bacteria were similar for both wavelengths. With riboflavin, a statistically significant elimination was observed for both 412 and 450 nm (p < 0.001). At both dosages, the mean reduction was more pronounced with the presence of riboflavin than without it. Using the higher dose, CFU reduction was 99% and 98%, respectively, for 412 and 450 nm light. The bactericidal efficacy was high also in the deeper fluid layer (93%, higher dose). CONCLUSION: Riboflavin enhanced the antibacterial effect on the exposed MRSA strain of blue light for both 412 and 450 nm blue light. This indicates that blue light could be considered for possible implementation in deep corneal infections.

Photodynamic UVA-riboflavin bacterial elimination in antibiotic-resistant bacteria.

BACKGROUND: To evaluate the bactericidal effect of clinical ultraviolet A (UVA) settings used in photoactivated chromophore for infectious keratitis (PACK)-collagen cross-linking (CXL) in antibiotic-resistant and non-resistant bacterial strains. METHODS: Well-characterized bacterial strains from clinical isolates, without and with antibiotic resistance, were studied in a pairwise comparison. The evaluated pathogens were Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacteria were dispersed in PBS and diluted to a concentration of approximately 4 × 105 /ml. Riboflavin was added to a concentration of 0.01%. By spreading the solution on a microscope slide, a fluid film layer, with a thickness of around 400 mm, was formed and UVA exposure followed. Eight separate exposures were made for each strain (n = 8). The degree of elimination in resistant and non-resistant pathogens was compared. RESULTS: The bactericidal efficacy of exposure differed between the tested microorganisms, and the mean elimination ranged between 60 and 92%, being most extensive in both of the evaluated Pseudomonas strains and least in the E. faecalis strains. Similar reductions were seen in antibiotic-resistant and non-resistant strains, with the exception of S. aureus, in which the resistant strain metchicillin-resistant Staphylococcus aureus (MRSA) was eradicated in a greater extent than the non-resistant strain (P = 0.030). CONCLUSION: UVA-riboflavin settings used in PACK-CXL are effective in reducing both antibiotic-resistant and non-resistant bacteria. Antibiotic resistance does not appear to be protective against the photooxidative exposure.

The efficiency of cross-linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light.

PURPOSE: To determine bacterial eradication using numerous riboflavin concentrations and different ultraviolet light A (UVA) radiant and exposure time in an experimental model. METHODS: Dilutions of Staphylococcus epidermidis were mixed with riboflavin at varying concentrations (0.007­0.09%). Effects on bacterial growth were evaluated after 0, 3, 6, 30 and 60 min of UVA exposure (irradiance 30 and 3 mW/cm2). Standard settings of UVA were compared with high-power UVA approach. Different fluid thicknesses of the exposed dilutions were also examined to improve the model. RESULTS: Bacterial eradication (%) was increased after 60 compared with 30 min of UVA exposure for concentrations of 0.03­0.07% but not for 0.09% riboflavin.There was a significant difference between the efficacy between 0.03 and 0.09% and eradication dropped from 80%to 50%(p = 0.01).A correlation could be calculated for the amount of riboflavin at 60 min of UVA and the ability to kill bacteria(p = 0.01). The antibacterial effect was more pronounced when the tested bacterial suspension thickness was reduced. High-power UVA method was less potent in microbial elimination, eradicating only 60%of bacteria after 6 min versus 97­99%after 60 min in the low-power setting, compared with respective controls (p = 0.02). CONCLUSIONS: In these in vitro experiments, a longer UVA exposure time in combination with lower riboflavin levels were found to be favourable in killing bacteria as compared to the standard cross-linking settings. Further studies are needed to evaluate the clinical relevance of these findings.

Corneal cross-linking in 9 horses with ulcerative keratitis.

BACKGROUND: Corneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting. RESULTS: Nine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4-26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis. CONCLUSIONS: CXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species.

Comparison of UVA- and UVA/riboflavin-induced growth inhibition of Acanthamoeba castellanii.

PURPOSE: To investigate whether ultraviolet light (UVA) at 365 nm can inhibit/eliminate Acanthamoeba growth and if riboflavin would potentiate such an association. METHODS: Acanthamoeba castellanii in a fluid medium with a concentration of approximately 1.7 × 10(4) protozoa/ml were prepared with (0.01 %) and without riboflavin. Exposure of UVA (dose 5.475 J/cm(2)) took place twice, with each illumination period followed by culturing of 10 µl in peptone yeast-extract glucose (PYG) medium for 7 days. Every suspension prepared had a non-exposed control solution. Determination of Acanthamoeba was conducted daily, by count in Burker chamber days 4 through 7 after exposure. Statistical analysis was done by repeated-measurement ANOVA and post-hoc analysis for unpaired samples. RESULTS: The exposure of ultraviolet light resulted in an inhibited growth of Acanthamoeba compared to the non-exposed solutions, with a statistically significant reduction over time (p = 0.0003). The addition of riboflavin did not amplify the effect, and there were no tendencies for an interaction effect between UVA and riboflavin. CONCLUSIONS: The antiprotozoal effect of the UVA wavelength, utilized in CXL, is solely mediated by ultraviolet light, and riboflavin does not seem to amplify the antimicrobial efficacy.

UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study.

BACKGROUND: The aim of this work as to investigate the photochemical interaction used in corneal crosslinking (CXL) as the primary therapy for bacterial keratitis. METHODS: A prospective non-randomized study was conducted including 16 patients with a clinical diagnosis of bacterial keratitis. No patient had any prior antibiotic treatment for the current infection. Photography and microbial culturing of the infected cornea were performed. Riboflavin was topically administered for 20 min and ultraviolet light (UVA) exposure settings for treatment of keratoconus were used. After the procedure, clinical examinations were done at least once daily until signs of improvement had been established. The frequency of examinations was thereafter reduced. Antibiotic therapy was initiated if infectious progression was suspected. The trial was registered at ISCRTN.org (no: 21432643). RESULTS: All eyes responded to the photochemical treatment with improvement in symptoms and signs of reduced inflammation. Epithelial healing was achieved in all cases. Antibiotic administration was necessary in two cases. One patient required a human amniotic membrane transplant. CONCLUSIONS: This trial illustrates that photosensitization of riboflavin using UVA at 365 nm has the potential to induce healing in patients with microbial keratitis. The results from the treatment of these 16 patients with corneal ulcers indicate that UVA-riboflavin photochemical therapy merits a controlled study in order to assess its efficacy and safety compared to antibiotics.

Vasoproliferative retinal tumours in a Swedish population.

PURPOSE: To describe the clinical appearance and the visual outcome of a cohort of patients with vasoproliferative retinal tumours (VPRTs) that were diagnosed and treated between 2002 and 2007 at the University Hospital of Örebro. METHODS: Nine patients with diagnosed VPRTs were included in a retrospective study. The mean age at the time of diagnosis was 50.2 years (range 7-74 years). Follow-up time ranged between 14 and 83 months (mean 42.6). Nine out of ten eyes received cryotherapy; six eyes were also treated with photocoagulation. One patient was treated with intravitreal injections of ranibizumab (Lucentis(®)) and another was referred for brachytherapy. Because of persisting macular oedema, one eye was treated with intravitreal injection of triamcinolon. RESULTS: Of the treated eyes, one had anterior uveitis, six had macular oedema at baseline and four had an exudative retinal detachment at the time of diagnosis. Seven eyes underwent vitrectomy because of epiretinal membranes. Visual acuity at diagnosis was 0.21 (mean) (range 0.02-0.6) and at latest check-up 0.30 (mean) (range light perception (LP)-1.0), with improvement in six eyes and deterioration in two. Two out of four patients with retinal detachment were successfully treated surgically. CONCLUSION: VPRTs are benign intraretinal changes. Several complications are associated with this condition. All patients in this study had symptom-giving tumours and six patients (six eyes) already had profound macular oedema at presentation. In these cases, when complications have already developed, the final visual prognosis is poor, thereby making it important to detect these tumours early. The patient who received anti-vascular endothelial growth factor (VEGF; Lucentis) therapy showed a slow improvement and distinct regression in exudations during the follow-up time. However, no increase in visual acuity was seen. At latest examination a peripheral exudative retinal detachment was still observed. Whether anti-VEGF treatment is effective, as either an alternative or complementary therapy, must be established in the future.

Infectious keratitis treated with corneal crosslinking.

PURPOSE: To describe 7 eyes with severe infectious keratitis treated using collagen crosslinking (CXL) with riboflavin. MATERIALS AND METHODS: Seven eyes of 6 patients with severe infectious keratitis were treated with corneal crosslinking. Three patients were contact lens users. Symptom duration before CXL ranged between 0 and 7 days. Corneal melting was present in all cases. Photodocumentation of the keratitis was carried out and repeated at follow-up. All but 1 patient received topical antibiotic treatment in addition to the CXL treatment. CXL was conducted according to the standardized protocol for keratoconus. RESULTS: In all but 1 eye, patients experienced improvement in symptoms within 24 hours. Two patients reported no symptoms whatsoever at this time. Corneal melting was arrested and complete epithelialization was achieved in all cases. In the 2 eyes with hypopyon, this regressed completely within 2 days after the CXL. Follow-up ranged between 1 and 6 months. DISCUSSION: Our experience based on the above and other cases suggest that CXL could be an effective tool in battling difficult cases of infectious keratitis. This treatment could present many advantages but will need further investigation.

Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA).

BACKGROUND: To evaluate the antibacterial efficacy of photo-activated riboflavin using Ultraviolet A (UVA) on three bacterial strains commonly detected in keratitis. METHODS: Three bacterial strains (Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa) were cultured on blood/hematin-agar plates and dispersed in PBS. Dispersion was done of 10 microl of bacterial stock-solutions in 90 microl of RPMI, where different riboflavin molarities had been added, to achieve a bacterial concentration of 1-4 x 10 (4)/ml. Riboflavin end molarities before illumination were 0, 100, 200, 300 and 400 microM. Each solution had a negative control. The solutions were illuminated with UVA (365 nm) for 30 minutes (5.4 J/cm(2)) and then continued for a total time of 60 minutes (10.8 J/cm(2)). A count of CFU was conducted after incubation and results compared. RESULTS: In all tested strains, a slight decrease of bacteria was seen when exposed to UV for 30 minutes. A doubling of the UV dose showed a marked decrease of bacterial count in all bacteria tested. The combination of UV and riboflavin showed a more extensive reduction of CFU, confirming an interaction effect between UV and riboflavin. CONCLUSION: Riboflavin photo-activation using UVA (365 nm) can achieve an extensive eradication of bacteria, and the combination is more potent in reducing bacterial number than UV alone.