Interleukin-1beta tear concentration in glaucomatous and ocular hypertensive patients treated with preservative-free nonselective beta-blockers

PURPOSE: To evaluate the ocular surface inflammatory response to the presence of preservatives in nonselective beta-blocker eyedrops. DESIGN: Prospective, crossover, single-masked, randomized clinical study. METHODS: STUDY POPULATION: Twenty primary open angle glaucoma or ocular hypertensive patients were divided in two groups, one treated with preservative-free timolol 0.5% (group 1) and the other with preserved timolol 0.5% (group 2) eyedrops. After 60 days of therapy and 3 more weeks of washout, the two groups switched to the other therapy. PROCEDURE: At each visit,basal tear samples were collected from the inferior conjunctival fornix for the determination of interleukin (IL)-1 tear concentrations by an enzyme-linked immunosorbent assay. Intraocular pressure measurement, conjunctival hyperemia, superficial punctate keratitis, and tear film breakup time were evaluated. MAIN OUTCOME MEASURE: IL-1 concentration in tears following the use of preserved eyedrops. RESULTS: IL-1 tear concentrations increased significantly in both groups, compared with baseline values,during preserved timolol therapy. There were no statistically significant changes in hyperemia and superficial punctate keratitis throughout the study in either group.A statistically significant breakup time reduction was observed in both groups after 30 days and after 60 days of preserved therapy. CONCLUSION: The use of preservatives in timolol 0.5% eyedrops leads to tear film instability and ocular surface inflammatory changes documented by a reduction of breakup time and an increase of IL-1 tear concentrations.Preservative-free beta-blockers are preferable for long-term hypotensive therapy to prevent ocular surface inflammation

Interleukin-1beta tear concentration in glaucomatous and ocular hypertensive patients treated with preservative-free nonselective beta-blockers

PURPOSE: To evaluate the ocular surface inflammatory response to the presence of preservatives in nonselective beta-blocker eyedrops. DESIGN: Prospective, crossover, single-masked, randomized clinical study. METHODS: STUDY POPULATION: Twenty primary open angle glaucoma or ocular hypertensive patients were divided in two groups, one treated with preservative-free timolol 0.5% (group 1) and the other with preserved timolol 0.5% (group 2) eyedrops. After 60 days of therapy and 3 more weeks of washout, the two groups switched to the other therapy. PROCEDURE: At each visit,basal tear samples were collected from the inferior conjunctival fornix for the determination of interleukin (IL)-1 tear concentrations by an enzyme-linked immunosorbent assay. Intraocular pressure measurement, conjunctival hyperemia, superficial punctate keratitis, and tear film breakup time were evaluated. MAIN OUTCOME MEASURE: IL-1 concentration in tears following the use of preserved eyedrops. RESULTS: IL-1 tear concentrations increased significantly in both groups, compared with baseline values,during preserved timolol therapy. There were no statistically significant changes in hyperemia and superficial punctate keratitis throughout the study in either group.A statistically significant breakup time reduction was observed in both groups after 30 days and after 60 days of preserved therapy. CONCLUSION: The use of preservatives in timolol 0.5% eyedrops leads to tear film instability and ocular surface inflammatory changes documented by a reduction of breakup time and an increase of IL-1 tear concentrations.Preservative-free beta-blockers are preferable for long-term hypotensive therapy to prevent ocular surface inflammation

Seksualni razvoj i reproduktivni ciklus raže okatice Atlantoraja cyclophora (Regan, 1903), (Chondrichthyes: Rajidae: Arhynchobatinae) u južnom Brazilu

Specimens of Atlantoraja cyclophora were collected monthly from commercial fishing landings at Guarujá, São Paulo State, Brazil, from March 2005 to April 2006 at depths between 10 and 146 m. Males ranged from 13.3 to 58.5 cm TL (n = 396). Both the smallest mature male and the largest immature male were 47.0 cm long. Males’ size-at-50% maturity was calculated to be 46.3 cm. Females ranged from 11.5 to 68.0 cm (n = 401). The smallest mature and the largest immature female were 51.6 and 53.0 cm long respectively. For the females, size-at-50% maturity was calculated to be 53.2 cm. In the males the hepatosomatic and gonadosomatic indices varied between 0.48 (August) and 3.54 (November) and between 0.15 (November) and 1.45 (June) respectively, with no significant variation for the fourteen-month period. In the females the hepatosomatic and gonadosomatic indices varied from 1.55 and 6.30 3.54 (both for April 2006) and from 0.08 (December) to 4.41 (October) respectively, with no significant difference among months. Egg-bearing females were found in all months with proportions varying from 0.03 (March) to 0.67 (April). Both males and females undergo an annual cycle, with slight seasonal variations in reproductive activity and a peak in the proportion of egg bearing females between April and July.Jedinke raže okatice, Atlantoraja cyclophora prikupljene su mjesečno iz gospodarskih lovina u Guarujáu, država São Paulo, Brazil, od ožujka 2005. do travnja 2006. na dubinama od 10 do 146 metara. Duljina mužjaka kolebala je od 13.3 do 58.5 cm TL (n=396). Najmanji spolno zreli mužjak i najveća spolno nezrela ženka bili su dugi 47.0 centimetara. Izračunata dužina mužjaka pri stadiju 50% zrelosti populacije je iznosila 46.3 cm. Dužina ženki se kretala u rasponu od 11.5 do 68.0 cm (n=401). Najmanja spolno zrela i najveća nezrela ženka su bile dugačke 51.6 cm, odnosno 53.0 cm. Izračunata dužina ženki pri stadiju 50% zrelosti populacije je iznosila 53.2 cm.Kod mužjaka su hepatosomatski i gonadosomatski indeks kolebali od 0.48 (kolovoz) i 3.54 (studeni) i između 0.15 (studeni) i 1.45 (lipanj) bez značajnih kolebanja tijekom razdoblja od četrnaest mjeseci. Kod ženki su hepatosomatski i gonadosomatski indeks kolebali od 1.55 do 3.54 (oba u travnju 2006.) i između 0.08 (prosinac) i 4.41 (listopad), bez značajnijih mjesečnih kolebanja. Ženke s jajima su bile nazočne tijekom svih mjeseci u razmjerima koji su kolebali od 0.03 (ožujak) do 0.67 (travanj). I mužjaci i ženke prolaze kroz svoj godišnji ciklus, sa neznatnim sezonskim kolebanjima u reproduktivnoj aktivnosti i maksimumom u proporciji ženki s jajima između travnja i srpnja

Prevention of Dermatologic Side Effects of Bimatoprost 0.03% Topical Therapy

PURPOSE: To investigate the efficacy of reducing the drop-skin contact to prevent dermatologic side effects of bimatoprost 0.03% topical therapy. DESIGN: Prospective, randomized, single-blinded, internally controlled study. METHODS: Enrolled subjects started bimatoprost 0.03% therapy once at night in both eyes and were instructed to wipe selectively only one eye (eye 1) with an adsorbent pad during and after drops administration for four months. The fellow eye acted as the internal control. Eyelash growth, regional skin hypertrichosis, and pigmentation on the periocular skin were assessed at baseline and during the four months of follow-up. RESULTS: A lower incidence of eyelash growth and skin pigmentation in the inferonasal pericanthal region were observed in eye 1. The incidence of pigmentation in the inferotemporal skin region and skin hypertrichosis were similar in the two eyes. CONCLUSION: The reduction of the drop,skin contact affects the regional incidence and the extent of dermatologic skin changes that are related to bimatoprost 0.03% topical therapy

Exploring the Heidelberg Retinal Tomograph 3 diagnostic accuracy across disc sizes and glaucoma stages: a multicenter study

To investigate and compare the diagnostic accuracy of the Heidelberg Retinal Tomograph 3 (HRT3) diagnostic algorithms and establish whether they are affected by optic disc size and glaucoma severity

Learning effect of humphrey matrix frequency doubling technology perimetry in patients with ocular hypertension

Aim: To evaluate the learning effect of Frequency Doubling Technology (FDT) perimetry using the Humphrey Matrix-FDT perimetry (Matrix) 24-2 full-threshold program on patients with 7 ocular hypertension experienced with standard automated perimetry. Methods: Twenty-four patients with Ocular hypertension underwent 5 full-threshold Matrix tests at intervals of 5 2 days. Learning effect was defined as an improvement at results for duration, perimetric indices, foveal sensitivity, Glaucoma Hemifield Test, and the number of points with a P < 5% and < 1% in the total and pattern deviation maps. Eccentricity, hemifield, and quadrant sensitivities were also addressed as Sources of differences in learning effect. Test-retest variability was also calculated for each repetition as the mean of the point-to-point interindividual standard deviations. Results: A learning effect was demonstrated for mean defect (P = 0.031, analysis of variance) and foveal sensitivity (P = 0.009) and it only affected the first test for both parameters. All the other parameters did not show any significant learning effect. The effect was independent From eccentricity and quadrant or hemifield sensitivities. Conclusions: The results of this study demonstrate that the learning effect for Matrix-FDT is mild and it may affect only the first test. Caution is needed in the analysis of the first Matrix-FDT examination and retest may be advisable in the presence of low mean defect

Levels of plasma homocysteine in pseudoexfoliation glaucoma.

BACKGROUND: To examine levels of serum homocysteine (Hcy), vitamin B12 and folic acid in patients with pseudoexfoliation glaucoma (PEXG), primary open-angle glaucoma (POAG), and healthy control subjects. METHODS: This study included 36 patients with PEXG, 40 with POAG, and 40 age-matched healthy subjects. Fasting plasma Hcy concentrations and levels of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay; values exceeding 14 μm/l were considered elevated. RESULTS: Mean plasma Hcy was significantly higher in PEXG (16.55 ± 7.23 μm/l) compared with POAG (13.91 ± 3.61 μm/l) and controls (13.12 ± 5.13 μm/l) (p = 0.03 and p = 0.0007 respectively). There were no statistical differences in serum vitamin B12 and folic acid levels among PEXG, POAG and control subjects (p > 0.05). A moderate, although statistically significant, relationship between Hcy and folic acid levels was found in the PEXG group (R(2) = 0.23, p = 0.003). Hcy levels were found not to be related with folic acid or vitamin B12 in either POAG or control subjects. CONCLUSIONS: In this study, plasma Hcy is significantly higher in PEXG group than the POAG and control groups. Hyper-Hcy might play a role in the pathogenesis of PEXG. Hyper-Hcy may be an independent factor stressing vasculopathy in addition to pseudoexfoliation, so might be a modifiable risk factor for PEXG

Optic nerve head and fibre layer imaging for diagnosing glaucoma

Background The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma. Objectives To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage. Search methods We searched several databases for this review. The most recent searches were on 19 February 2015. Selection criteria We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or Data collection and analysis We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level. Main results We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear. Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study. The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio. Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people. Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD &lt; -6 db versus 0.64 (0.60 to 0.69) for MD &gt;=-6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P &lt; 0.0001 for the difference in relative DOR). Authors' conclusions The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base. We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data

Retinal functional changes measured by frequency-doubling technology in patients treated with hydroxychloroquine.

BACKGROUND: Antimalarial drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) are mainly used in the treatment of rheumatologic diseases, and their use may be associated with irreversible retinal toxicity. Previous studies indicate early paracentral visual field loss (Humphrey 10-2) in patients taking HCQ". These paracentral defects appear before changes in other clinical parameters as visual acuity and fundoscopy. The mechanism of CQ toxicity remains unclear. It was reported that toxic doses of CQ administered for as long as 4.5 years to Rhesus monkeys caused an initial dramatic effect on ganglion cells, followed later by photoreceptors and RPE degeneration. The purpose of this study is to explore early retinal functional changes measured by frequency-doubling technology (FDT) in patients treated with hydroxychloroquine (HCQ). METHODS: Forty-eight eyes of 48 subjects treated with hydroxychloroquine (HCQ), with no signs of retinal toxicity, and 36 eyes of 36 age and sex-matched healthy subjects were enrolled in this cross-sectional, prospective, observational, case control study. Functional testing included frequency-doubling Humphrey-matrix perimetry (FDP), white-on-white Humphrey visual field perimetry (HFA), using the 24-2 and 10-2 threshold programs, multifocal electroretinogram (mfERG, Veris 4.9) and low contrast sensitivity (CS) measurement. RESULTS: FDP mean deviation (MD) was found to be significantly reduced in HCQ-treated patients compared to controls both in the 24-2 (-1.38 ± 2.41 dB vs 0.21 ± 1.83 dB, p < 0.01) and in the 10-2 program (-0.97 ± 2.88 dB vs 0.15 ± 1.72 dB, p < 0.01). FDP pattern standard deviation (PSD) was found to be significantly worse in HCQ-treated patients compared to controls both in the 24-2 (2.70 ± 0.65 dB vs 2.41 ± 0.31 dB, p < 0.01 and in the 10-2 program (2.86 ± 0.48 dB vs 2.48 ± 0.39 dB, p < 0.01). HFA PSD and CS was also significantly reduced in HCQ patients, while response amplitude densities (RAD) were similar between patients and controls. A statistically significant difference in the ratio of the 5°-10° RAD and the 0°-2.5° RAD (0.31 ± 0.08 vs 0.36 ± 0.07 respectively, p < 0.05) was found between groups. CONCLUSION: Frequency doubling perimetry could be useful to detect early retinal impairment in patients treated with hydroxychloroquine