Ras signaling pathway in the chemopreventive action of different ratios of fish oil and corn oil in experimentally induced colon carcinogenesis.

Dietary factors play a significant role in colon cancer. The essential polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-6 PUFAs exert inverse effect on cancer. This study was designed to understand the mechanism of chemopreventive action of different ratios of fish oil (FO) and corn oil (CO) in colon carcinoma. Wistar rats were divided into 3 groups: Group 1 received purified diet whereas Groups 2 and 3 received modified diet with FO:CO (1:1) and FO:CO (2.5:1), respectively. The groups were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH)/wk for 4 wk. Animals sacrificed 48 h after last injection constituted initiation phase and that sacrificed after 16 wk constituted post-initiation phase. Differential effect of different ratios of FO and CO was analyzed in isolated colonocytes. In both phases, DMH treatment showed an increase in pan Ras, Raf, MEK1/2, extracellular signal regulated kinase (Erk)1/2, and c-fos levels. Akt levels were increased in post-initiation phase only. Treatment with FO + CO (1:1) + DMH decreased pan Ras, MEK1/2 and Erk1/2 levels in post-initiation phase whereas Raf and c-fos were decreased in both phases. Treatment with FO + CO (2.5:1) + DMH decreased Ras, Raf, MEK1/2, Erk1/2, and c-fos levels in both phases. Akt was decreased in post-initiation phase only. The chemo-preventive action of FO and CO may be mediated by time- and dose-dependent effect.

Inhibitory effects of maternal smoking on the development of severe retinopathy of prematurity.

PURPOSE: In this study, the effects of maternal smoking along with other clinical risk factors in developing severe retinopathy of prematurity (ROP) were evaluated. DESIGN: A case-control study. METHODS: Records of newborn infants with an estimated postmenstrual age of 32 weeks or less (n=86) were reviewed. ROP grading was evaluated in accordance with the International Classification of Retinopathy of Prematurity. Severe ROP was diagnosed when it progressed to stage 3 with plus disease. The factors were first evaluated using a univariate logistic regression analysis between the groups of severe and non-severe ROP, followed by a multivariate logistic regression analysis using STATA version 10 and R version 2.71. RESULTS: A low birth weight, a long duration of artificial ventilation and oxygen supplementation, presence of chronic lung disease, and absence of maternal smoking were found to be significantly associated with severe ROP in the univariate logistic regression analysis. In the multivariate logistic regression analysis, maternal smoking was revealed as a significant factor independently associated with the incidence of severe ROP. CONCLUSIONS: An inhibitory effect of maternal smoking against developing severe ROP is suggested. The mechanism by which smoking may reduce the incidence of severe ROP needs to be further investigated.

Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy.

PURPOSE: To evaluate the safety and efficacy of intravitreal injection of bevacizumab advanced to vitrectomy for severe proliferative diabetic retinopathy. METHODS: Eight eyes of six patients (33-64 years old, all male patients) with severe proliferative diabetic retinopathy were investigated. An intravitreal injection of 1.25 mg bevacizumab was performed 3-30 days prior to planned vitrectomy. RESULTS: All cases showed minimum bleeding during surgical dissection of fibrovascular membrane. Two cases receiving bevacizumab 7 days before the surgery showed strong fibrosis and adhesion of fibrovascular membrane, resulted in some surgical complications. The cases having intravitreal bevacizumab for shorter time did not show extensive fibrosis. CONCLUSIONS: The pretreatment of bevacizumab is likely effective in the vitrectomy for severe PDR. The appropriate timing of vitrectomy after bevacizumab injection should be further evaluated.

Alkaptonuria and intramedullary calcification.

Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria (dark urine), relentlessly progressive arthritis and ochronosis. We have documented a case with typical features of alkaptonuria along with intramedullary calcification which has not been reported in the literature before.

Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma.

AIMS: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. METHODS: Genomic DNA was extracted from whole blood of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese origin. RESULTS: Fifteen microsatellite markers within and/or near to the GLC1B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. CONCLUSION: The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma.

Disagreement between Heidelberg Retina Tomograph and optical coherence tomography in assessing optic nerve head configuration of eyes with band atrophy and normal eyes.

BACKGROUND/AIMS: To evaluate to what extent the optic nerve head (ONH) parameters as measured with Heidelberg Retina Tomograph (HRT) differed from those measured with optical coherence tomography (OCT) in eyes with compressive optic neuropathy (CON) that had band atrophy (BA) of the optic disc. METHODS: A total of 30 eyes from 19 patients with BA due to chiasmal tumour and 162 eyes from 162 normal subjects were examined with HRT and Stratus OCT using the fast optic nerve scan protocol. Parameters measured by the two devices, including the disc area, cup/disc (C/D) area ratio, cup area, cup volume, rim area and rim volume, were compared between the eyes of BA patients and controls. Bland-Altman plots were used to evaluate agreement for each parameter between OCT and HRT in both groups of eyes. Intermethod discrepancy of the measurements for each parameter was compared between the two groups of eyes. RESULTS: Eyes with BA had smaller cup and larger rim parameters than control eyes when measured with HRT, whereas they had significantly larger cup and significantly smaller rim parameters than control eyes when measured with OCT. HRT measurements tended to be consistently lower in the C/D area ratio and cup area and higher in the rim area and rim volume than OCT measurements for both control eyes and eyes with BA. The intermethod discrepancy for all the parameters except the disc area was significantly larger in eyes with BA than in control eyes. CONCLUSION: The increased optic disc excavation was detected with OCT but not with HRT in CON eyes with BA of the optic disc. Thus, the distinct algorithms used by these two modalities affected the measurements of ONH parameters, particularly when assessing optic discs with temporal rim thinning.

Intravitreal triamcinolone will cause posterior subcapsular cataract in most eyes with diabetic maculopathy within 2 years.

PURPOSE: To determine the incidence of cataract following intravitreal triamcinolone (IVTA) for diabetic macular oedema. METHODS: Prospective, non-randomised, interventional cohort case series. A total of 27 eyes of 27 patients with diabetic macular oedema received an intravitreal injection of 4 mg (0.1 ml) of triamcinolone acetonide inferotemporally through the pars plana under direct vision. In 20 patients the fellow eye served as control, whereas seven patients had both eyes injected (not simultaneously). Seven patients had a repeat (second) injection in the same eye. The main outcome measures were cataract and intraocular pressure (IOP) rise of at least 5 mmHg (IOP responder). RESULTS: The mean follow-up time was 18.9 months (range 13-29 months). A total of 22 (81%) of 27 eyes developed cataract during the follow-up period, of which 20 (74%) were posterior subcapsular in nature. None of the 20 uninjected fellow eyes developed posterior subcapsular cataract. Mean time to cataract formation was 16.2 months. In the seven patients who had both eyes injected, mean time to cataract formation was 16.5 and 17.1 months in the first and second eye, respectively. Mean time to cataract formation in seven eyes receiving a repeat second injection was 17.9 months. There was no significant difference in cataract formation between IOP responders (85%) and non-responders (79%) (P=1.00, Fisher's exact test). Uneventful cataract surgery was performed in six eyes of five patients. CONCLUSION: This study demonstrates that given appropriate long-term follow-up, the majority of patients, even after a single IVTA injection, will go on to develop cataract, of which posterior subcapsular will be by far the most common.

The -174G/C interleukin-6 promoter polymorphism influences the development of macular oedema following uncomplicated phacoemulsification surgery.

AIM: To determine whether the functional -174 G/C interleukin-6 gene polymorphism is a risk factor for the development of cystoid macular oedema (CMO) following routine uncomplicated phacoemulsification surgery in patients with no established risk factors. METHODS: A total of 40 patients who underwent routine phacoemulsification surgery as part of a randomised controlled trial comparing the use of postoperative steroid drops against a single sub-tenon injection of triamcinolone were genotyped for the IL-6 -174G/C polymorphism. All patients underwent fluorescein angiography at 30 days and anterior chamber flare measurements pre-operatively and at day 1, 7, and 30. RESULTS: Angiographic CMO developed in 14 patients of the 40 studied. 9 out of the 14 patients carried the GG genotype (Fisher's exact test P=0.05, Hazard ratio for GG genotype; 4.05 (1.02-16.00)). There was no difference in flare measurements between the GG and Non-GG (GC/CC) group. The two groups were otherwise well matched in terms of age, sex, phacoemulsification energy used intraoperatively, and proportion of patients receiving postoperative triamcinolone or steroid drops. CONCLUSION: The -174G/C interleukin-6 promoter gene variant appears to modulate the response to phacoemulsification surgery and to influence the development of postoperative CMO. These data suggest a genetic predisposition to this complication.

Different transitions of multifocal electroretinogram recordings between patients with age-related macular degeneration and polypoidal choroidal vasculopathy after photodynamic therapy.

AIM: To compare and evaluate the transitions in retinal function after photodynamic therapy (PDT) between age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) using multifocal electroretinograms (mfERGs). METHODS: 10 eyes with choroidal neovascularisation (CNV) secondary to AMD and 11 eyes with CNV secondary to PCV were included in the study. mfERGs were recorded before PDT, and 1 week and 3 months after PDT. mfERG recordings were acquired by a Veris system (V.3.1.3) using a 103 hexagon stimulus. The first-order kernel was used to calculate amplitudes and latencies. Mean amplitudes and latencies from two central rings rated 0-4 degrees of visual angle were analysed and compared with each disease. RESULTS: In AMD, the mean first negative peak (N1) amplitudes tended to decrease, and the mean first positive peak (N1P1) amplitudes reduced to significant levels (p = 0.047) 1 week after PDT. 3 months after PDT, there were no significant differences in the mean N1 and N1P1 amplitudes compared with pre-PDT values. In PCV, there were no significant changes in the mean N1 and N1P1 amplitudes 1 week after treatment. However, 3 months after PDT, mean amplitudes showed significant increases in N1 (p = 0.008) and N1P1 (p = 0.006) amplitudes compared with pre-PDT values. CONCLUSIONS: mfERG recording transitions are different between patients with AMD and those with PCV. In patients with AMD, these results may show transient impairments in retinal function 1 week after PDT, but in those with PCV, the efficacy of PDT is superior to the impairment after PDT.

Intravitreal triamcinolone improves vision in eyes with chronic diabetic macular oedema refractory to laser photocoagulation.

PURPOSE: To evaluate the clinical and visual outcome of an intravitreal injection of triamcinolone in patients with diabetic macular oedema refractory to laser treatment. MATERIAL AND METHODS: Prospective, interventional nonrandomised case series of 24 eyes of 24 patients that underwent intravitreal injection of 4 mg triamcinolone for chronic diabetic macular oedema refractory to previous laser treatment. All patients had best corrected visual acuity (bcva) on the LogMAR scale, near vision, slit-lamp biomicroscopy for the presence of clinically significant macular oedema, and intraocular pressure check at 1, 3, and 6 months. RESULTS: The average duration of macular oedema before the injection was 38.2 months (range=6-120 months) with the mean number of laser treatments before the injection being 2.2 (range=1-5). The visual acuity improved in 19 of the 23 (83%) eyes at 1 month, 16 of the 21 eyes (76%) at 3 months and six of 11 eyes (55%) at 6 months follow-up. The mean bcva improved by an average of 10, nine, and six letters, respectively, compared to the baseline at 1, 3, and 6 months (P=0.0002 at 1 month and 0.001 at 3 months with the Wilcoxon signed-ranked test). The intraocular pressure rose by an average of 2.4, 2.8, and 2.7 mmHg at the same follow-up visits. CONCLUSION: Intravitreal triamcinolone appears to be promising in the short term, for improving the vision in eyes with chronic diabetic macular oedema unresponsive to conventional laser treatment. Randomised controlled trials utilising varying doses of steroid are now required to define optimum treatment regimens.

Improved visual acuity and macular thickness 1 week after intravitreal triamcinolone for diabetic macular oedema.

PURPOSE: To evaluate the clinical and volumetric improvement 1 week after an injection of intravitreal triamcinolone acetonide in eyes with diabetic macular oedema. METHODS: Seven phakic eyes of seven diabetic patients diagnosed with clinically significant macular oedema were treated with a single 4-mg intravitreal injection of triamcinolone acetonide (0.1 ml). LogMAR best corrected visual acuity (logMAR BCVA), best corrected reading ability (RA), and central macular thickness (CMT) with optical coherence tomography (OCT) were assessed prior and 1 week subsequent to treatment. RESULTS: Mean improvement in logMAR BCVA was 0.146 (P=0.03). Mean reduction in CMT was 150.9 mum (P=0.02, Wilcoxon signed-rank test). Mean improvement in RA was 3 lines. CONCLUSION: Reduction in macular oedema was demonstrated on OCT at 1 week, in most cases associated with improvement in central visual function, in particular, reading ability. Total resolution of diabetic macular oedema may occur at 1 week following intravitreal steroid injection.

Does the site of filtration influence the medium to long term intraocular pressure control following microtrabeculectomy in low risk eyes?

AIMS: To evaluate the influence of varying surgical site on the medium to long term intraocular pressure (IOP) control in patients undergoing unenhanced small flap trabeculectomy (microtrabeculectomy) in eyes at low risk of failure. METHODS: A retrospective non-concurrent analysis was performed on two cohorts of patients who underwent unenhanced microtrabeculectomy at different sites by a single surgeon (SAV). The first cohort of eyes was part of a trial to study the astigmatic effect of microtrabeculectomy (results published elsewhere) and all had flaps centred at the 12 o'clock meridian (superior flaps). The second cohort consisted of eyes with flaps created on either side of the 12 o'clock-that is, superonasal in left eyes and superotemporal in right eyes. All case notes were reviewed for the preoperative and presenting IOPs, the number and duration of antiglaucoma medication use preoperatively and, postoperatively, any intraoperative, early, or late postoperative complications. All IOPs measured at 6 months and then yearly intervals were recorded. The baseline characteristics and IOPs at each follow up were compared between the eyes with the superonasal and superotemporal flaps of the non-12 o'clock group against those with superior flaps in the 12 o'clock group up to a maximum of 72 months. Survival was assessed by the site of microtrabeculectomy, with failure considered as any IOP above 22 and 15 mm Hg with or without medications. RESULTS: All patients had a minimum follow up of 12 months and 12/17 patients in the 12 o'clock group and 17/28 in the non-12 o'clock group completed the full follow up of 72 months. The IOPs at all points in time were lower in the left eyes with superonasal flaps compared to both the superior and the superotemporal groups. This difference was statistically significant between the three groups to the end of 4 years (p = 0.001) and remains clinically significant thereafter with the mean last recorded IOPs of 15.9, 12.4 (p = 0.03), and 14.3 mm Hg in the superior, superonasal and superotemporal groups respectively, with a smaller mean number of drops in the non-12 o'clock group. Kaplan-Meier curves showed a significantly better outcome for the cutoff IOP of 15 mm Hg in the superonasal group (p = 0.003) compared with both the other groups. CONCLUSION: Eyes with superonasal flaps achieve and maintain lower IOPs when compared with both the superior and superotemporal flaps. The results suggest that, when a low target IOP is desired, the site of surgery in an unenhanced filtering procedure should be superonasally sited.

Matrix metalloproteinases induction by pseudomonal virulence factors and inflammatory cytokines in vitro.

The pathogenesis of pseudomonal keratitis was investigated by focusing on induction and activation of matrix metalloproteinases (MMPs) by pseudomonal virulence factors and proinflammatory cytokines. Corneal lesions and MMP induction in vivo were evaluated in rabbit corneas infected with a clinical isolate of Pseudomonas aeruginosa. Effects of pseudomonal virulence factors [elastase, alkaline protease, exotoxin A and lipopolysaccharide (LPS)], tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta on MMP induction and activation were further examined in vitro in rabbit corneal fibroblasts (RCF) and human fibrosarcoma (HT1080) cells using reverse transcriptase-polymerase chain reaction (RT-PCR), zymography and immunoblotting. Corneal ulcers with typical ring abscesses were observed 12-24 h after infection, and MMPs, particularly MMP-9, were upregulated in infected corneas. Pseudomonal elastase caused the most extensive damage to both cell types. RCF treated with pseudomonal exoproteases or LPS expressed and secreted MMP-9. Exotoxin A had no effect on MMP expression. Both IL-1beta and TNF-alpha augmented MMP-9 expression in HT1080 cells. Pseudomonal elastase proteolytically activated MMP-2 and MMP-9 released from the cells. In conclusion, corneal destruction seen with P. aeruginosa infections may result from enhanced expression of MMPs by corneal stromal cells stimulated with pseudomonal exoproteases and proinflammatory cytokines and the proteolytic activation of MMPs by pseudomonal elastase.

Cataract surgery in patients with advanced Mooren's ulcer.

BACKGROUND: We describe 2 patients with severe Mooren's ulcer who underwent phacoemulsification and intraocular lens implantation surgery. The clinical features of this disease are highlighted. CASE: A detailed study of the ocular and laboratory findings in these patients, together with a review of the literature, is presented. OBSERVATIONS: There was a visually rewarding outcome after phacoemulsification and intraocular lens implantation were performed, and Mooren's ulcer did not recur. CONCLUSION: We conclude that phacoemulsification-aspiration and intraocular lens implantation surgery with a small incision can be successfully performed in patients with Mooren's ulcer after complete control of inflammation with topical and oral steroid therapy, or with ocular reconstruction surgery when required.

Fundus changes corresponding to visual field defects after vitrectomy for macular hole.

OBJECTIVE: Visual field defects are one of the complications of macular hole surgery, and mechanical retinal damage induced by infusion air is a proposed causative factor of this complication. In this study, we examined the fundus to see whether the changes observed corresponded to postoperative visual field defects. DESIGN: Observational case series. PARTICIPANTS: Seventeen eyes of 17 patients who had postoperative visual field defects after vitrectomy for idiopathic macular hole were examined. METHODS: The fundus was examined by ophthalmoscopy and by fluorescein and indocyanine green angiography. MAIN OUTCOME MEASURES: Fundus changes corresponding to postoperative visual field defects. RESULTS: In eight eyes, detectable fundus changes were observed, including regional mottling and degeneration of the retinal pigment epithelium, filling delay of the choroidal circulation, subretinal fibrosis, and epiretinal membrane formation. These findings corresponded exactly to the visual field defects observed. Although the visual field defects had been detected shortly after surgery, fundus changes were detected, on average, more than 8 months after surgery. CONCLUSIONS: Fundus changes become apparent after surgery, and they are progressive. Therefore, it is important to examine eyes with visual field defects for a follow-up period of several years.

[Three ocular sarcoidosis patients examined by indocyanine green angiography].

PURPOSE: To assess the findings of indocyanine green angiography(IA) in patients with ocular sarcoidosis. SUBJECTS AND METHODS: Three active ocular sarcoidosis patients with various retinochoroidal findings diagnosed by biopsy or systemic examination. Two patients were diagnosed pathologically and one patient was diagnosed clinically. IA & fluorescein angiography(FA) were performed before and after treatment with systemic steroid administration. RESULTS: IA revealed hyperfluorescence surrounding the presumed granulomatous lesions. This hyperfluorescence disappeared immediately after the treatment. FA showed hyperfluorescence continuing even after therapy. CONCLUSIONS: It is purposed that the ring-form hyperfluorescence in IA is due to accelerated vascular permeability in the active sarcoid granuloma. IA, which vividly reflects activity of sarcoid lesions, is an important tool for clinical evaluation of ocular sarcoidosis.