Crossing the Death Valley of publication process in cornea and ocular surface diseases: from abstracts presented at the Association for Research in Vision and Ophthalmology annual meeting to full-text manuscripts / Atravessando o Vale da Morte do processo de publicação sobre doenças da córnea e da superfície ocular: de resumos apresentados no Encontro Anual da Associação de Pesquisa em Visão e Oftalmologia até artigos completos

ABSTRACT Purpose: This study was conducted to analyze the profile and publication rate of abstracts in indexed journals presented in the cornea section at the Association for Research in Vision and Ophthalmology Annual Meeting and to further identify potential predictive factors for better outcomes. Methods: Abstracts accepted for presentation at the 2013 Association for Research in Vision and Ophthalmology Annual Meeting in the cornea section were sought via PubMed and Scopus to identify whether they had been published as full-text manuscripts. First author's name, time of publication, journal's name, and impact factor were recorded. A multivariate regression was performed to explore the association between variables and both the likelihood of publication and the journal's impact factor. A Kaplan-Meier analysis was performed to evaluate the time course of publication of abstracts. Results: Of the 939 analyzed abstracts, 360 (38.3%) were published in journals with a median impact factor of 3.4. The median time interval between abstract submission and article publication was 22 months. The multivariate analysis revealed that abstracts were more likely to be published if they were funded (OR=1.482, p=0.005), had a control group (OR=1.511, p=0.016), and had a basic science research scope (OR=1.388, p=0.020). The journal's impact factor was higher in funded studies (β=0.163, p=0.002) but lower in multicenter studies (β=-0.170, p=0.001). The Kaplan-Meier analyses revealed significant differences in the publication time distribution for basic science vs clinical abstracts (χ2=7.636), controlled vs uncontrolled studies (χ2=6.921), and funded vs unfunded research (χ2=13.892) (p<0.05). Conclusion: Almost 40% of Association for Research in Vision and Ophthalmology abstracts were published within 5 years from submission. Funding support, basic research scope, and controlled design were the determinants of better outcomes of publication.(AU)

RESUMO Objetivo: Analisar o perfil e a taxa de publicação em periódicos indexados de resumos apresentados na seção de córnea da reunião anual da Association for Research in Vision and Ophthalmology - ARVO, para identificar potenciais fatores preditivos com objetivo de obter melhores resultados. Métodos: Artigos que foram aceitos para apresentação no encontro anual da Association for Research in Vision and Ophthalmology - ARVO 2013 na seção de córnea foram pesquisados via PubMed e Scopus para identificar se haviam sido publicados como manuscritos com texto integral. Nome do primeiro autor, data de publicação, nome da revista e fator de impacto foram registrados. Foi feita uma regressão multivariada para estabelecer uma associação entre as variáveis e a chance de publicação e o fator de impacto da revista. Foi utilizado o método Kaplan-Meier para analisar o tempo da apresentação até a publicação dos artigos. Resultados: Dos 939 artigos analisados, 360 (38.3%) foram publicados em revistas com um fator de impacto médio de 3.4. O intervalo de tempo entre a submissão do resumo e a publicação do artigo teve como mediana 22 meses. Na análise multivariada, resumos tinham mais chance de publicação se tinham algum tipo de financiamento (OR=1.482, p=0.005), tinham grupo controle (OR=1.511, p=0.016) e estavam no âmbito da pesquisa científica básica (OR+1.388, p=0.020). O fator de impacto da revista era maior em estudos financiados (β=0.163, p=0.002) e mais baixo naqueles multicêntricos (β=-0.170, p=0.001). A análise Kaplan-Meier mostrou diferenças significativas na distribuição de tempo até a publicação de resumos de ciência básica vs clínicos (χ2=7.636), com grupo controle vs sem grupo controle (χ2=6.921) e financiados vs não financiados (χ2=13.892) (p<0.05). Conclusão: Aproximadamente 40% dos resumos apresentados no encontro da Association for Research in Vision and Ophthalmology - ARVO foram publicados dentro de 5 anos da submissão. Financiamento, pesquisa no âmbito da ciência básica e presença de grupo controle foram fatores determinantes para melhores resultados em relação à chance de publicação.(AU)

Crossing the Death Valley of publication process in cornea and ocular surface diseases: from abstracts presented at the Association for Research in Vision and Ophthalmology annual meeting to full-text manuscripts.

PURPOSE: This study was conducted to analyze the profile and publication rate of abstracts in indexed journals presented in the cornea section at the Association for Research in Vision and Ophthalmology Annual Meeting and to further identify potential predictive factors for better outcomes. METHODS: Abstracts accepted for presentation at the 2013 Association for Research in Vision and Ophthalmology Annual Meeting in the cornea section were sought via PubMed and Scopus to identify whether they had been published as full-text manuscripts. First author's name, time of publication, journal's name, and impact factor were recorded. A multivariate regression was performed to explore the association between variables and both the likelihood of publication and the journal's impact factor. A Kaplan-Meier analysis was performed to evaluate the time course of publication of abstracts. RESULTS: Of the 939 analyzed abstracts, 360 (38.3%) were published in journals with a median impact factor of 3.4. The median time interval between abstract submission and article publication was 22 months. The multivariate analysis revealed that abstracts were more likely to be published if they were funded (OR=1.482, p=0.005), had a control group (OR=1.511, p=0.016), and had a basic science research scope (OR=1.388, p=0.020). The journal's impact factor was higher in funded studies (ß=0.163, p=0.002) but lower in multicenter studies (ß=-0.170, p=0.001). The Kaplan-Meier analyses revealed significant differences in the publication time distribution for basic science vs clinical abstracts (χ2=7.636), controlled vs uncontrolled studies (χ2=6.921), and funded vs unfunded research (χ2=13.892) (p<0.05). CONCLUSION: Almost 40% of Association for Research in Vision and Ophthalmology abstracts were published within 5 years from submission. Funding support, basic research scope, and controlled design were the determinants of better outcomes of publication.

Longitudinal Corneal Endothelial Cell Changes in Patients Undergoing Hematopoietic Stem Cell Transplantation.

PURPOSE: To evaluate longitudinally corneal endothelial cell changes in patients undergoing hematopoietic stem cell transplantation (HSCT) and to further investigate possible correlations with hematological and ocular characteristics. METHODS: Prospective observational study conducted at a single center. All patients underwent a comprehensive ophthalmological examination, before and after HSCT, including slitlamp examination, Schirmer test, tear breakup time, ocular surface staining, specular microscopy of corneal endothelium, and Ocular Surface Disease Index questionnaire. RESULTS: Twenty-five patients undergoing HSCT and 25 age- and sex-matched controls were included. At baseline, hematological patients showed significantly lower values of endothelial cell density (ECD) compared with those of controls (2514.5 ± 390.2 vs. 2723.7 ± 298.0 cells/mm, P = 0.038). After HSCT, ocular surface disease index score significantly increased (P = 0.020) and tear breakup time significantly decreased (P = 0.036). Conversely, no significant changes were found in Schirmer test and corneal fluorescein staining (always P > 0.05). Eight patients (32%) developed ocular graft-versus-host disease (GVHD). ECD values significantly decreased after HSCT (from 2514.5 ± 390.2 to 2409.5 ± 330.9 cells/mm, P = 0.009). The decrease in ECD values after HSCT was more pronounced in patients with ocular GVHD compared with those without (231.1 ± 188.8 vs. 45.6 ± 156.5, P = 0.016). No significant correlations between the changes in ECD and hematological and ocular characteristics were found (always P > 0.05). CONCLUSIONS: Hematological patients showed a lower endothelial cell count already before HSCT, compared with controls. After HSCT, the endothelial cell count further significantly decreased, particularly in patients who developed ocular GVHD.

Longitudinal Analysis of Infrared Meibography in Patients Undergoing Hematopoietic Stem Cell Transplantation.

PURPOSE: To evaluate meibomian gland (MG) changes in patients undergoing hematopoietic stem cell transplantation (HSCT) by infrared meibography and to further investigate possible correlations with hematological characteristics. METHODS: Thirty-three patients were included: infrared meibography of the lower eyelid, Schirmer test, tear break-up time, ocular surface staining, and Ocular Surface Disease Index questionnaire were conducted before (V0) and 4 months after HSCT (V1). A paired samples t test was used to compare parameters before and after HSCT. A mixed analysis of variance was used to assess the effect of hematological characteristics on changes of MG loss (MGL) after HSCT. RESULTS: MGL and corneal staining significantly increased after HSCT (respectively, from 24.3% ± 10.1% to 32.2 ± 15.0 and from 1.2 ± 1.5 to 2.0 ± 1.7; always P < 0.011), whereas tear break-up time significantly decreased (from 6.6 ± 4.2 seconds to 3.2 ± 2.2; P < 0.001). At V1, 19 patients (57.6%) belonged to ocular graft-versus-host disease severity grade 0, 8 (24.2%) to grade I, and 6 (18.2%) to grade II. The percentage of MGL at V0 and the increase of MGL from V0 to V1 did not differ between patients who developed ocular graft-versus-host disease and those who did not (always P > 0.05). At V1, MGs' quality reduced in 16 patients (48.5%), remained unchanged in 14 (42.4%), and improved in 3 (9.1%). The increase of MGL after HSCT was higher in patients receiving myeloablative conditioning regimen (P = 0.005). CONCLUSIONS: MG function, loss, and quality significantly worsened after HSCT. Myeloablative conditioning regimen was associated with higher MGL.

CHOROIDAL VASCULARITY INDEX QUANTIFICATION IN GEOGRAPHIC ATROPHY USING BINARIZATION OF ENHANCED-DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHIC SCANS.

PURPOSE: To evaluate choroidal structural changes occurring over time in geographic atrophy (GA) secondary to age-related macular degeneration using choroidal vascularity index (CVI). METHODS: Enhanced-depth imaging optical coherence tomography scans of 34 patients with GA and 32 control subjects were retrospectively analyzed. Data were collected at baseline and after a mean follow-up of 18.3 ± 8.3 months. Choroidal images were binarized using the ImageJ software, and the luminal area and stromal area were segmented. Choroidal vascularity index was defined as the ratio of luminal area to total choroid area. RESULTS: Patients with GA showed significantly lower values of CVI, total choroid area, luminal area, and subfoveal choroidal thickness compared to control subjects (65.83 ± 3.95 vs. 69.33 ± 3.11, P < 0.001; 0.400 ± 0.239 mm vs. 0.491 ± 0.132, P = 0.006; 0.263 ± 0.152 mm vs. 0.340 ± 0.094, P = 0.002; 185.2 ± 79.8 µm vs. 216.8 ± 58.8 µm, P = 0.036, respectively). Best-corrected visual acuity was significantly correlated only with choroidal thickness (R = -0.509; P = 0.002). During the follow-up period in patients with GA, subfoveal choroidal thickness decreased from 185.2 ± 79.8 to 152.2 ± 73.1 (P = 0.001), stromal area increased from 0.138 ± 0.090 mm to 0.156 ± 0.068 (P = 0.028), and CVI decreased from 65.83 ± 3.95 to 62.24 ± 3.63 (P < 0.001). CONCLUSION: This study showed for the first time that CVI is reduced in patients with GA, and that this metric further worsened during the follow-up period.

Blood derived treatment from two allogeneic sources for severe dry eye associated to keratopathy: a multicentre randomised cross over clinical trial.

AIM: To compare the efficacy of cord blood and peripheral adult donor blood serum eyedrops, controlled for growth factor content, in the treatment of severe dry eye diseases (DED) resistant to conventional therapy. METHODS: This was a multicentre randomised, double-masked, cross-over clinical trial. Sixty patients diagnosed as severe DED, associated to persistent corneal epithelial defects were randomised and equally assigned to group A (treated with cord blood serum (CBS)) or group B (treated with PBS), eyedrops administered eight times/day for 1 month. Primary outcome was the pretreatment and post-treatment change in corneal fluorescein staining. Secondary outcomes included the pretreatment and post-treatment change in Ocular Surface Disease Index (OSDI) questionnaire and Visual Analogue Score (VAS) of subjective symptoms, Schirmer I test, tear break-up time and conjunctival staining. Patients with relapse in signs or symptoms after further 2 months switched to the remaining group for one additional month. Data were statistically analysed (p<0.05). RESULTS: Corneal staining was more significantly reduced after the CBS treatment, both VAS and OSDI score reduction was observed in both groups, but group A reported significantly less grittiness and pain. Nineteen patients shifted in the crossover period, the within individual comparison confirmed a better recovery in the CBS treatment period. Reduction in epithelial damage was positively associated with epidermal growth factor, transforming growth factorα and platelet-derived growth factor content. Levels of interleukins (IL-13) were positively associated with symptom decrease. CONCLUSIONS: Overall, DED signs improved after both CBS and PBS treatments, with potential advantages of CBS for subjective symptoms and corneal damage reduction. CLINICAL TRIAL REGISTRATION: NCT03064984.

Ocular surface status in patients with hemifacial spasm under long-lasting treatment with botulinum A toxin: A comparative fellow eye study.

Purpose: The purpose of this study was to assess the effect of long-lasting botulinum A toxin injections on ocular surface parameters and to further investigate the relationship between these parameters and the duration of the treatment. Methods: In this retrospective study, patients with unilateral hemifacial spasm who were receiving botulinum A toxin injections for at least 1 year were analyzed. Healthy contralateral eyes acted as controls. The ocular surface examination included Ocular Surface Disease Index questionnaire, Schirmer test type I, tear film break-up time (TFBUT), tear osmolarity, corneal sensitivity, and corneal fluorescein staining. Results: Twenty-six patients (6 males and 20 females; mean age 76.4 ± 8.9 years) were included in the study. The mean duration of the treatment was 7.2 ± 5.4 years, and the mean frequency of injections was of one every 3.3 ± 0.4 months. TFBUT, Schirmer test, and corneal sensitivity were significantly lower in the eye homolateral to hemifacial spasm compared with the contralateral one (5.9 ± 3.2 vs 7.5 ± 4.2 s, P = 0.001; 6.2 ± 3.4 vs 9.2 ± 6.6 mm, P = 0.031; 50.8 ± 3.7 mm vs 52.3 ± 2.9 mm, P = 0.048, respectively). One month after the last injection, TFBUT further decreased from 5.9 ± 3.2 to 2.3 ± 1.2 s (P = 0.028). A significant positive correlation was found between the duration of treatment and tear osmolarity (ρ = 0.542, P = 0.025). Conclusion: Patients with hemifacial spasm under long-lasting treatment with serial botulinum A toxin injections showed a reduction in tear film production and stability, as well as corneal sensitivity in the treated eye compared with the contralateral one. Tear film stability further decreased 1 month after the last injection.

In Vivo Confocal Microscopy Automated Morphometric Analysis of Corneal Subbasal Nerve Plexus in Patients With Dry Eye Treated With Different Sources of Homologous Serum Eye Drops.

PURPOSE: To investigate the comparative effect of allogeneic peripheral blood serum (allo-PBS) and cord blood serum (CBS) eye drops on the status of the corneal subbasal nerve plexus in patients with dry eye disease by using an automated analysis system of in vivo confocal microscopy images. METHODS: This prospective, randomized, double-blind study included 30 patients with severe dry eye disease assigned to receive allo-PBS (group 1) or CBS (group 2) eye drops 8 times a day for 30 days. The following in vivo confocal microscopy parameters were calculated with ACCMetrics before (visit 1 [V1]) and after treatment (visit 2 [V2]): corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal nerve total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fractal dimension (CNFrD). RESULTS: In overall patients, the values of corneal nerve fiber density, corneal nerve fiber length, and CNFrD significantly increased, whereas the value of corneal nerve fiber width significantly decreased at V2 compared with V1 (respectively, 20.4 ± 7.9 vs. 17.4 ± 10.1 n/mm; 13.5 ± 4.0 vs. 12.0 ± 5.1 mm/mm; 1.466 ± 0.046 vs. 1.475 ± 0.033; and 0.022 ± 0.002 vs. 0.023 ± 0.002; all P < 0.05). In the subanalysis according to the treatment type, the increase of CNFrD value from V1 to V2 was higher in group 2 compared with group 1 (respectively, from 1.455 ± 0.041 to 1.471 ± 0.030 and from 1.479 ± 0.050 to 1.481 ± 0.035; P = 0.030). CONCLUSIONS: Overall, both treatments significantly improved corneal subbasal nerve plexus parameters, and in particular, nerve density, length, width, and fractal dimension. Treatment with CBS eye drops was associated with a higher increase of CNFrD compared with allo-PBS.

Longitudinal Morphometric Analysis of Sub-Basal Nerve Plexus in Contralateral Eyes of Patients with Unilateral Neurotrophic Keratitis.

Objectives: To investigate longitudinally corneal sub-basal nerve plexus (SNP) by means of in vivo confocal microscopy (IVCM) in the contralateral eye (CE) of patients with unilateral neurotrophic keratitis (NK) secondary to central nervous system (CNS) diseases who underwent different treatments. Methods: Ten patients with NK and 10 matched controls were included. In 7 NK patients, conservative treatment maintained unchanged the clinical picture over the 1-year follow-up (Group 1), while NK progressed in 3 patients who underwent direct corneal neurotization (Group 2). IVCM scans of SNP of NK patients were acquired in CE at baseline (V0) ad after 1-year follow-up (V1). All images were analyzed with the automated software "ACCMetrics" and compared with controls. The following IVCM corneal nerve parameters were calculated at V0 and V1 with ACCMetrics: fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). Results: At V0, significantly lower mean values of CNFD and CNBD, and higher values of CNFW were detected in CE of NK patients compared to controls (respectively, 16.9 ± 8.7 vs 25.0 ± 8.3 n/mm2, P= .029; 19.3 ± 13.8 vs 33.8 ± 18.9 n/mm2, P= .023; 0.022 ± 0.002 vs 0.020 ± 0.001 mm/mm2, P< .001). From V0 to V1, all IVCM metrics of CE remained unchanged in Group 1, while they improved in Group 2. Conclusions: Contralateral eye of patients with unilateral NK secondary to CNS disease showed lower CNFD and CNBD and higher CNFW compared to controls. Unlike conservative treatment, direct corneal neurotization was able to improve SNP metrics also in CE.

Choroidal Vascular Changes in Arteritic and Nonarteritic Anterior Ischemic Optic Neuropathy.

PURPOSE: To compare choroidal vascularity index (CVI) in patients with arteritic anterior ischemic optic neuropathy (A-AION), nonarteritic anterior ischemic optic neuropathy (NA-AION), and control subjects. DESIGN: Retrospective cross-sectional study. METHODS: This study was conducted at the Ophthalmology Unit of the S.Orsola-Malpighi University Hospital (Bologna, Italy). Macular and optic nerve head optical coherence tomography (OCT) scans of 20 patients with A-AION secondary to giant cell arteritis (biopsy-proven), 20 patients with NA-AION, and 20 control subjects were acquired with Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany). Images were binarized using ImageJ software, and total choroid area (TCA), luminal area (LA), and stromal area (SA) were segmented. The main outcome measure was CVI, defined as the ratio of LA to TCA. RESULTS: Patients with A-AION showed a significantly lower macular and peripapillary CVI compared to both patients with NA-AION (respectively, 67.17 ± 2.35 vs 69.66 ± 4.18, P = .048; 63.51 ± 3.29 vs 67.67 ± 3.07, P < .001) and control subjects (respectively, 67.17 ± 2.35 vs 70.00 ± 2.95, P = .021; 63.51 ± 3.29 vs 68.69 ± 3.19, P = .002). Conversely, no significant difference in macular and peripapillary CVI was found between patients with NA-AION and controls (respectively, P = .942 and P = .570). After adjustment for age, the difference of peripapillary CVI among groups remained statistically significant (P < .001), while the difference in macular CVI did not (P = .060). CONCLUSIONS: Macular and peripapillary CVI are reduced in patients with A-AION. These parameters may be useful to quantitatively evaluate choroidal vascular dysfunction in A-AION, serving as a new additional diagnostic tool to distinguish A-AION from NA-AION.

In vivo confocal microscopy morphometric analysis of corneal subbasal nerve plexus in dry eye disease using newly developed fully automated system.

PURPOSE: To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software "ACCMetrics," and to further investigate its diagnostic performance in discriminating DED patients. METHODS: IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann-Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls. RESULTS: Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/mm2; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm2; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm2; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm2; always p < 0.024). CNFW value had the highest diagnostic power in discriminating DED patients (AUC = 0.828). When the diagnosis of DED was made based on either CNFW or CNBD, the sensitivity was 97.4% and the specificity 46.7%. CONCLUSIONS: The software ACCMetrics was able to rapidly detect SNP alterations occurring in the setting of DED and showed good diagnostic performance in discriminating DED patients.

Meibomian Gland Dropout in Hematological Patients Before Hematopoietic Stem Cell Transplantation.

PURPOSE: To perform qualitative and quantitative analysis of meibomian gland (MG) dropout in hematological patients before hematopoietic stem cell transplantation (HSCT) and to correlate it with both ocular surface and hematological characteristics. METHODS: This prospective study included 46 consecutive patients undergoing HSCT and 30 age- and sex-matched healthy controls. Noninvasive meibography of the lower eyelid, meiboscore (Pult scale), Schirmer test type I, tear film breakup time, and corneal and conjunctival staining were measured. Subjective symptoms were scored by the Ocular Surface Disease Index. The dry eye diagnosis was ascertained according to TFOS DEWS II Criteria. Hematological data included diagnosis (acute leukemias vs. other malignancies), stage of the disease, time from diagnosis to ophthalmological examination, and previous therapy (chemotherapy, radiotherapy, or autograft). RESULTS: Hematological patients presented a significantly lower tear film breakup time and a higher meiboscore compared with controls (respectively 4.8 ± 3.0 seconds vs. 11.0 ± 3.0 and 2.0 ± 1.1 vs. 0.9 ± 0.4; P < 0.001). Conversely, other parameters did not differ between both groups. Dry eye was diagnosed in 14 out 46 hematological patients (30.4%). MG loss was significantly higher in hematological patients than in controls (29.8% ± 15.0% vs. 21.2 ± 13.0; P = 0.007) and was higher in the nasal third compared with both central and temporal thirds (respectively, 39.8% ± 21.4% vs. 18.5 ± 15.6 and 25.1 ± 18.3; P < 0.0001). The diagnosis of acute leukemia (ß = 0.449; P = 0.003) and the history of previous chemotherapy (ß = 0.444; P = 0.003) were associated with lower MG loss. CONCLUSIONS: Hematological patients presented significantly reduced MG areas even before HSCT, particularly those affected by nonacute malignancies. The topographical pattern of MG dropout resembles that of conventional dry eye.