Fehim Esen

Double-Organ Bias in Published Randomized Controlled Trials of Glaucoma.

Purpose:Most of the statistical tests used in significance testing are based on the assumption that each data entry is independent from other entries, however, we observe that in many articles researchers include data from 2 eyes as independent variables while performing these statistical tests. The aim of this study was to formally survey the prevalence of the above-mentioned “double-organ bias” in randomized controlled trials (RCT) of glaucoma. Materials and Methods:We did a PubMed search with the terms “glaucoma” and limitations “Humans” and “Randomized Controlled Trials” in 15 highest-impact-factor ophthalmology journals between November 2002 and November 2012. We only included RCTs published as an original article, where the aim was treating glaucoma. Two independent observers (M.K. and A.S.E.) read through each article and classified the articles according to treatment modality (medical, laser, or surgical) and presence of double-organ bias. Results:The PubMed search yielded 270 articles. A total of 130 articles qualified for the survey. Eighty-five of the RCTs were medical studies, 11 were laser studies, and 34 studies evaluated the outcome of a surgical procedure. In 17 of the 130 articles (13.1%), double-organ bias was found. Prevalence of the double-organ bias was not significantly different between medical (12.9%), laser (14.7%), and surgical (9.1%) studies. Conclusion:Double-organ bias was observed around 13.1% of the published RCTs, leading to inaccurate statistical testing.

Darbepoetin Alpha Ameliorates Neuronal Damage in a Rat Model of Acute Ethanol Intoxication

ABSTRACT Objective: Acute ethanol intoxication has been shown to cause oxidative damage in many organ systems including the brain. Erythropoietin has antioxidant effects and prevents neuronal damage in the animal model of ischemic brain injury. In this study, we aimed to investigate the effects of darbepoetin alpha, an analog of erythropoietin with a longer half-life and higher in vivo activity, on ethanol-induced acute brain injury. Methods: Forty-eight Wistar albino rats were allocated to four groups. The first group received ethanol treatment (E), the second group was treated with ethanol and darbepoetin (ED), the third group received only saline treatment (S), and the fourth group received both saline and darbepoetin treatment (SD). Plasma S100-β and neuron-specific enolase (NSE) levels were measured. Histopathological evaluation of the brains was performed. Results: The plasma S100-β and NSE levels were significantly lower in group ED compared with group E. In group E, we have observed focal red-neuron formation at the granular layer of the dentate gyrus. We did not observe any histopathological changes in the other groups (ED, S, and SD). Conclusion: Our findings suggest that darbepoetin alpha has neuroprotective effect in acute ethanol intoxication, possibly through its antioxidant effect.

An Audit of Behcet's Syndrome Research: A 10-year Survey

Objective. Data suggest that the use of disease control groups and proper use of power calculations were neglected in published reports. We surveyed these and other methodological shortcomings in reports published within the last decade about one specific topic, Behcet’s syndrome. We reason that recognizing such methodological shortcomings will lead to better quality clinical and basic science articles. Methods. Articles published in the 15 highest impact factor journals on rheumatology, ophthalmology, dermatology, and general medicine between January 1999 and January 2009 were searched for original reports on Behcet’s syndrome. Study designs (study types and time element), control groups, demographic data, use of power calculations, and reporting of negative results were specifically tabulated. Results. Most studies on Behcet’s syndrome were cross-sectional (83%). Prospective longitudinal studies were few (7%). In a considerable proportion of papers (21%), some basic demographic data were missing. Power calculations were rare (3%) even in randomized controlled trials and were not considered at all in clinical hypothesis-testing. Disease control groups were present in slightly over half of clinical and laboratory original research, while just 13% of genetic association studies included disease controls. Only 12% of all reports concerned mainly negative outcomes. Conclusion. A considerable number of the published research articles have methodological weaknesses. The generalizability of what we observed in Behcet’s syndrome to other research topics needs to be formally studied.

Decreased subfoveal choroidal thickness and failure of emmetropisation in patients with oculocutaneous albinism

Purpose The purpose of this work was to describe the choroidal structure in patients with oculocutaneous albinism (OCA). Methods 20 eyes of 10 patients with OCA and 14 eyes of 7 healthy controls were recruited for the study. Enhanced depth imaging optical coherence tomography (OCT) images of the subjects were taken. The choroidal thickness (CT) was measured from the outer boarder of the retinal pigment epithelium to the inner boarder of sclera at 500 µm intervals of a horizontal section from the optic disc. Statistical analysis was performed to evaluate variations in CT at subfoveal and peripapillary areas. Results In the fundoscopic examination and OCT imaging, the foveal light reflex was absent and the foveal pit could not be observed in all of the patients with OCA. The mean subfoveal CT of the patients with OCA was significantly thinner (242±56 µm) compared with healthy controls (349±70 µm) (p<0.001); while there was no statistically significant difference in the peripapillary CTs of the patients with OCA and controls (157±42 µm vs 151±31 µm respectively, p=0.77), indicating a localised abnormality of choroidal anatomy. Conclusions This study for the first time demonstrated that CT is decreased in patients with OCA at the subfoveal region. These data combined with the underdevelopment of the foveal pit indicate that there is a generalised developmental or genetic abnormality in the posterior pole of patients with OCA. This choroidal structural abnormality might be related to the previously reported failure of emmetropisation in these children. Further research is needed to understand choroidal metabolism and its relationship with these anatomical changes in albinism.

Peripapillary retinal leukemic infiltration associated with papilledema in a T-ALL patient without cranial or optic nerve involvement.

Purpose To present a rare case of bilateral peripapillary retinal leukemic infiltration associated with papilledema without retrobulbar optic nerve involvement in a patient with acute lymphoblastic leukemia (ALL). Methods This was a retrospective case report. Results A 24-year-old man with T-cell ALL and 2-month history of papilledema presented to our department with reduction of visual acuity in the left eye. Visual acuity was 20/60 in the right eye and hand movements in the left eye. Fundus examination revealed grade 3 papilledema, bilateral peripapillary leukemic infiltration, and intraretinal hemorrhages. Cranial magnetic resonance imaging did not show any sign of cranial mass or optic nerve involvement. Pulse steroid therapy and oral acetazolamide was started. At day 18, visual acuity improved to 20/40 in the right eye and 20/60 in the left eye, while papilledema improved to grade 1 and hemorrhages regressed. Conclusions To our knowledge, there is no other report of peripapillary leukemic infiltration in the absence of retrobulbar optic nerve involvement. We suspect that papilledema might have facilitated peripapillary retinal infiltration due to altered vascular permeability. The reverse could also be possible: leukemic infiltration leading to increase in vascular permeability may also contribute to papilledema.

Comment on Bilateral same-session intravitreal injections

Dear Editor,We have read the article by Abu-Yahgi et al[1]with great interest.The authors share their experience with bilateral same-session intravitreal injection of anti-vascular endothelial growth factors(anti-VEGF).They report a single case of endophthalmitis in a series of 342 injections of 74patients and compare their results with their 3634 cases of unilateral injections with 2 cases of endophthalmitis[1].There are some issues related with the article that may benefit from

Authors’ response: evaluation of choroidal thickness among patients with oculocutaneous albinism

We thank Chan et al 1 for their interest in our work and their valuable comments. The authors kindly reminded that diurnal variation choroidal thickness may influence our results. We agree that diurnal variation in choroidal thickness can influence the measurements performed by enhanced depth imaging optical coherence tomography (OCT).2 ,3 Unfortunately, our study was not initially designed to eliminate the influence of diurnal variation, as those studies were not available when we started our study. We examined most of the patients during the afternoon (between 12:00 and 17:00) due to logistical availability reasons and this …

THU0539 Less Emphasis on Self Critique among Basic Science Compared to Clinical Science Manuscripts in Rheumatology Literature

Background An honest self critique is or should be an important part of scientific output. Even though explicitly underlined in scientific authorship guidelines like CONSORT (1) and STROBE (2) we had the impression that many journal articles in rheumatology did not give this due importance. Furthermore we also had the impression that self critique was less frequent in basic than in clinical science articles. Objectives To formally quantify self critique in clinical and basic science articles separately in 3 widely read rheumatology journals. Methods The 2012 January, May and September issues of Ann Rheum Dis, Arthritis Rheum and Rheumatology were selected. All original, full articles with discussion sections were analyzed by 2 independent observers (FG, HY) to survey whether they were of mainly basic or clinical science content. Their discussion sections were electronically scanned to assess whether the word “limit” or its derivatives (i.e limits, limitations, etc.) (limit.der) were ever used and whether, when used, these words implied self critique. In addition each observer sought for the presence of any discussion sentences by which the authors had resorted to self critique regardless whether they had included the word “limit” or a “limit.der” A third observer (YY) had the final say in instances where the initial two observers disagreed whether an article had mainly clinical or basic science content. Results 231 articles were surveyed. 137 (59%) were of clinical and 94 (41%) of basic science content. The Table shows the number of articles that contained the word “limit” and/or a limit.der” in the discussion sections of these articles as well as the presence of any form of self critique which included the presence of the word “limit” or a “limit. der”. The statistically significant differences between the two kinds of articles persisted when each journal was assessed separately (data not given). In 4/231(1.7%) instances the word “limit” or a “limit.der” was used in a different context. Conclusions Around one half of the original articles in our leading rheumatology journals lacked self critique. This was significantly more pronounced in basic science manuscripts. We propose that such self critique should be highlighted perhaps even more in the scientific authorship guidelines especially in those related to basic science, including animal work. Also a higher priority should be given to its presence in peer review. References Altman DG, Schulz KF, Moher D, et al, CONSORT Group. Ann Intern Med 2001;134:663–94. von Elm E, Altman DG, Egger M, et al, STROBE Initiative. Lancet 2007;370:1453–7. Disclosure of Interest H. Yazici: None Declared, F. Gogus: None Declared, F. Esen: None Declared, Y. Yazici Grant/research support from: BMS, Genentech, Centocor, Celgene, Consultant for: Abbott, BMS, Celgene, Genentech, Horizon, Janssen, Pfizer, UCB