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.

Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study.

PURPOSE: To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN]) for the treatment of neurotrophic keratopathy (NK). DESIGN: Multicenter interventional prospective comparative case series. METHODS: This study took place at ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; and Santa Maria alle Scotte University Hospital, Siena, Italy. The study population consisted of consecutive patients with NK who underwent CN between November 2014 and October 2019. The intervention procedures included DCN, which was was performed by transferring contralateral supraorbital and supratrochlear nerves. ICN was performed using a sural nerve graft. The main outcome measures included NK healing, corneal sensitivity, corneal nerve fiber length (CNFL) measured by in vivo confocal microscopy (IVCM), and complication rates. RESULTS: A total of 26 eyes in 25 patients were included: 16 eyes were treated with DCN and 10 with ICN. After surgery, NK was healed in all patients after a mean period of 3.9 months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11 mm; P < .001) without differences between the 2 groups. The corneal sub-basal nerve plexus that was absent before surgery in all patients, except 4, become detectable in all cases (mean CNFL: 14.67 ± 7.92 mm/mm2 1 year postoperatively). No major complications were recorded in both groups. CONCLUSIONS: CN allowed the healing of NK in all patients as well as improvement of corneal sensitivity in most of them thanks to nerve regeneration documented by IVCM. One year postoperatively, DCN and ICN showed comparable outcomes.

In Vivo and Ex Vivo Comprehensive Evaluation of Corneal Reinnervation in Eyes Neurotized With Contralateral Supratrochlear and Supraorbital Nerves.

PURPOSE: To use an automated morphometric analysis system of in vivo confocal microscopy (IVCM) images for evaluating reinnervation occurring at the subbasal nerve plexus (SNP) after direct corneal neurotization (DCN) and to further report neurophysiological and histopathological findings. METHODS: Prospective interventional case series including 3 eyes with neurotrophic keratitis that underwent DCN. Deep anterior lamellar keratoplasty was performed 18 months after DCN in patient 1. The following evaluations were performed before and at 3, 6, and 12 months after DCN: clinical evolution of keratitis; corneal sensitivity; IVCM images of the SNP analyzed with "ACCMetrics;" neurophysiological study of corneal reflex. Protein gene product 9.5 immunofluorescence staining assay and transmission electron microscopy were conducted on the neurotized button excised during deep anterior lamellar keratoplasty. RESULTS: Complete healing was obtained in all patients by 3 months postoperatively. Corneal sensitivity was absent preoperatively in all eyes and improved after surgery, reaching an average value of 30 mm 1 year postoperatively. The corneal SNP was not visible at IVCM in any of the cases preoperatively and became visible by 3 months postoperatively, showing IVCM metrics comparable to normal contralateral eyes at 1 year. In all cases, neurophysiological evaluation showed a partial recovery of the electrical activity of the cornea. In patient 1, protein gene product (PGP) 9.5 staining of neurotized cornea showed nerve fascicles at the SNP, whereas transmission electron microscopy showed amyelinic nerve axons and nerve endings. CONCLUSIONS: The corneal SNP exhibited IVCM metrics comparable to the normal contralateral eye 1 year after DCN. Ex vivo histopathological assessment of neurotized corneas confirmed the presence of nerves with normal ultrastructure.

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.

Corneal biomechanical alterations in patients with chronic ocular Graft Versus-Host Disease.

PURPOSE: To compare corneal biomechanics between patients with ocular graft versus-host disease (oGVHD) and healthy subjects (controls), and to further correlate these values with ocular and hematological characteristics. MATERIALS AND METHODS: The following procedures were performed in oGVHD patients and controls: Schirmer test (ST), break-up time (BUT), corneal and conjunctival staining, tear matrix metalloproteinase-9 (MMP-9) assay (InflammaDry test, Rapid Pathogen Screening, Inc, Sarasota, FL). Corneal biomechanics were calculated by using ocular response analyzer (ORA, Reichert Instruments, Depew, New York, USA). The Mann-Whitney U test was used to compare continuous variables between oGVHD patients and controls. Correlations of corneal biomechanics with ocular and hematological parameters were examined using Spearman's correlation. RESULTS: A total of 45 oGVHD patients (mean age ± SD, 51.5 ± 7.1 years) and 34 controls (47.8 ± 6.1 years) were included. Patients with oGVHD showed significantly lower values of corneal hysteresis (CH) and corneal resistance factor (CRF) compared to controls (respectively, 9.4 ± 1.8 mmHg vs 11.6 ± 1.6 and 9.7 ± 1.4 mmHg vs 12.3 ± 1.3; always p<0.001). Twenty-nine of the oGVHD eyes (64.4%) were strong-positive for MMP-9, while 16 (35.6%) were weak-positive. Conversely, only 4 of the control eyes (11.8%) were weak-positive for MMP-9. In patients with oGVHD, CH was significantly correlated with corneal staining (Rs = -0.316, p = 0.035), conjunctival staining (Rs = -0.437, p = 0.003), ST (Rs = 0.390, p = 0.008), BUT (Rs = 0.423, p = 0.004), oGVHD severity grade (Rs = -0.383, p = 0.009), and MMP-9 positivity grade (Rs = -0.429, p = 0.003), while CRF was correlated only with corneal staining (Rs = -0.317, p = 0.034). CONCLUSIONS: Corneal biomechanics are reduced in patients with oGVHD, and CH is negatively correlated with disease severity grade and MMP-9 tear levels.

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.

Intraocular inflammation after Ultrasound Cyclo Plasty for the treatment of glaucoma.

This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty (UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes (Eye OP1). After treatment, the mean intraocular pressure (IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6 (all P<0.001). Mean laser flare-cell photometry value steeply increased after surgery from 12.1±7.5 to 64.1±53.9 ph/ms (P=0.001) at day 1, and then progressively decreased to respectively 60.6±49.7 at day 7, 43.5±38.5 at day 14 and 28.2±18.3 at month 1 (all P<0.05), returning at levels similar to baseline ones at month 3 and month 6 (respectively 16.7±6.2 and 12.8±10.2, both P>0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth (R=-0.568, P=0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.

Efficacy of Omega-3 Fatty Acid Supplementation for Treatment of Dry Eye Disease: A Meta-Analysis of Randomized Clinical Trials.

PURPOSE: To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease. METHODS: We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity. RESULTS: Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554-1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043-0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India. CONCLUSIONS: This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.

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.

Comparison among different diagnostic criteria for chronic ocular graft-versus-host disease applied with and without pre-transplant ophthalmological examination.

PURPOSE: To compare the proportion and the agreement rate in the diagnosis of chronic ocular graft-versus-host disease (GVHD) among three criteria applied with and without ophthalmological examination before hematopoietic stem cell transplantation (HSCT). METHODS: National Institutes of Health (NIH), International Consensus Criteria on ocular GVHD (ICCGVHD) and TFOS Dry Eye Workshop (DEWS) II criteria were used for the diagnosis of ocular GVHD according to two protocols: ophthalmological examination after HSCT (Protocol A), or before and after HSCT (Protocol B). Proportion of GVHD diagnosis and inter-rate agreement coefficient Kappa (K) among the criteria were calculated. RESULTS: One hundred nine patients undergone HSCT were included. NIH, ICCGVHD and DEWS II criteria diagnosed ocular GVHD in 14.7%, 17.4% and 59.6% of the patients (Protocol A), whereas in 11.9%, 15.6% and 33.0% of the HSCT patients (Protocol B). The coefficient K for the proportion of patients diagnosed with ocular GVHD by NIH and ICCGVHD criteria was K = 0.626 (Protocol A) and K = 0.615 (Protocol B). The K coefficient by NIH and DEWS II criteria was K = 0.144 (Protocol A), and K = 0.233 (Protocol B). The K coefficient by ICCGVHD and DEWS II criteria was K = 0.250 (Protocol A) and K = 0.499 (Protocol B). The K coefficient for ocular GVHD diagnosis applying Protocol A and B was K = 0.881 if NIH criteria were used, K = 0.933 if ICCGVHD criteria were used and K = 0.501 if DEWS II criteria were used. CONCLUSIONS: The diagnosis of ocular GVHD varied significantly in our cohort of hematological patients according to both the diagnostic criteria used and the visit protocols applied.

Ultrasound Cyclo-Plasty in Patients with Glaucoma: 1-Year Results from a Multicentre Prospective Study.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of ultrasound cyclo-plasty (UCP) for reducing intraocular pressure (IOP) in patients with glaucoma. METHODS: This is a multicentre prospective study conducted in 3 Italian glaucoma centres. UCP was performed by EyeOP1, which delivers ultrasound beams using 6 piezoelectric transducers activated for 4/6 s (first generation) or 8 s (second generation). Primary outcomes were the mean IOP reduction and the rates of success after 1 year. Secondary outcomes were the mean IOP reduction at each follow-up, and the reduction of the number of hypotensive medications. RESULTS: In total, 49 eyes from 47 patients were treated. One year postoperatively, the mean IOP had decreased from 27.7 ± 9.2 to 19.8 ± 6.9 mm Hg (p < 0.001), and the mean number of hypotensive drops and tablets had decreased from 3.2 and 0.5 to 2.3 and 0.2, respectively (p < 0.05). Postoperative IOP reduction was significantly related to preoperative IOP (r2 = 0.5034; p < 0.0001). Second-generation probes determined a significantly higher IOP reduction (p < 0.05). Qualified success was achieved in 25 eyes (51.1%) and complete success in 21 (42.9%), while failure was recorded in 12 (24.5%). CONCLUSIONS: UCP is safe and effective for reducing IOP. The procedure determines a greater IOP reduction in patients with higher preoperative IOP. Second-generation probes improve outcomes without detrimental effects on safety.

Neurotrophic keratitis: current challenges and future prospects.

Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described.

The Comparative Efficacy and Tolerability of Diclofenac 0.1% and Bromfenac 0.09% Ophthalmic Solutions after Cataract Surgery.

PURPOSE: To compare the efficacy and tolerability of diclofenac and bromfenac ophthalmic solutions as adjunctive therapy after cataract surgery. MATERIALS AND METHODS: This prospective randomized controlled study included 130 patients who underwent cataract surgery. One hundred patients were randomized to receive postoperatively diclofenac 0.1% (four times daily for 28 days, Group 1) or bromfenac 0.09% (twice daily for 14 days, Group 2) ophthalmic solutions in addition to steroid-antibiotic combination. Thirty patients instilled only steroid-antibiotic combination (Control Group 3). Laser flare-cell photometry and optical coherence tomography scans with central foveal thickness (CFT) measurement were performed before (V0) and 7 (V1), 14 (V2) and 28 days (V3) after surgery. Treatment tolerability was scored using the Ocular Comfort Grading Assessment. RESULTS: Laser flare-cell photometry values were significantly higher at V1, V2 and V3 compared to V0 in all the groups (respectively 13.3 ± 1.0, 12.7 ± 0.9 and 9.6 ± 0.9 vs 8.4 ± 0.6 ph/ms for Group 1; 13.4 ± 1.0, 12.7 ± 0.9 and 12.7 ± 1.0 vs 8.1 ± 0.6 for Group 2; 15.9 ± 0.8, 15.4 ± 0.7 and 14.5 ± 0.7 vs 7.5 ± 0.5 for Group 3) (p < 0.001); flare increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.001). CFT values were higher after surgery in all the three groups; the increase was significantly lower in Group 1 compared to Groups 2 and 3 (p < 0.0002). The percentage of symptoms-free patients after study treatment was significantly higher in Group 2 compared to Group 1 (respectively 74% vs 14% of the total; p < 0.001). CONCLUSION: The addition of diclofenac or bromfenac ophthalmic solutions contributed to further reduce both inflammation and cystoid macular edema after cataract surgery compared to steroid-antibiotic combination alone. Diclofenac appeared to be more effective in reducing postoperative intraocular inflammation with a more intense and prolonged regimen, while bromfenac more tolerated with lower daily dose and treatment duration.

In vivo assessment of changes in corneal hysteresis and lamina cribrosa position during acute intraocular pressure elevation in eyes with markedly asymmetrical glaucoma.

PURPOSE: To investigate the biomechanical response of the cornea, lamina cribrosa (LC), and prelaminar tissue (PT) to an acute intraocular pressure (IOP) increase in patients with markedly asymmetrical glaucoma and in healthy controls. PATIENTS AND METHODS: A total of 24 eyes of 12 patients with markedly asymmetrical primary open-angle glaucoma (POAG) and 12 eyes of 12 healthy patients were examined with spectral-domain optical coherence tomography (SD-OCT) and ocular response analyzer (ORA) at baseline and during acute IOP elevation by means of an ophthalmodynamometer. The displacement of the LC and PT and the change in corneal hysteresis (CH) and corneal resistance factor (CRF) were evaluated. RESULTS: Following a mean IOP increase of 12.3±2.4 mmHg, eyes with severe glaucoma demonstrated an overall mean anterior displacement of the LC (-6.58±26.09 µm) as opposed to the posterior laminar displacement in eyes with mild glaucoma (29.08±19.28 µm) and in healthy eyes (30.3±10.9; p≤0.001 and p=0.001, respectively). The PT displaced posteriorly during IOP elevation in all eyes. The CH decreased in eyes with severe glaucoma during IOP elevation (from 9.30±3.65 to 6.92±3.04 mmHg; p=0.012), whereas the CRF increased markedly in eyes with mild glaucoma (from 8.61±2.30 to 12.38±3.64; p=0.002) and in eyes with severe glaucoma (from 9.02±1.48 to 15.20±2.06; p=0.002). The increase in CRF correlated with the anterior displacement of the LC in eyes with severe glaucoma. CONCLUSION: Eyes with severe glaucoma exhibited a mean overall anterior displacement of the anterior laminar surface, while eyes with mild glaucoma and healthy eyes showed a posterior displacement of the LC during IOP elevation. The CH decreased significantly from baseline only in eyes with severe glaucoma, but the CRF increased significantly in all glaucomatous eyes. The CRF increase correlated with the anterior displacement of the LC in eyes with severe glaucoma.

Immunologic Stromal Rejection After Deep Anterior Lamellar Keratoplasty With Grafts of a Larger Size (9 mm) for Various Stromal Diseases.

PURPOSE: To evaluate the rate and outcomes of immunologic stromal rejection occurring after large deep anterior lamellar keratoplasty (DALK) and the effect of the underlying disease on the cumulative probability of rejection. METHODS: This was a retrospective chart review of all eyes that underwent a 9-mm DALK at Ospedali Privati Forlì (Forlì, Italy). On the basis of preoperative diagnosis, eyes were assigned to group 1: keratoconus, group 2: stromal disease with a low risk for rejection, or group 3: stromal disease with a high risk for rejection. The cumulative probability of experiencing a rejection episode over time was assessed by Kaplan-Meier analysis and was compared among the 3 groups using the log-rank test. Values of corrected distance visual acuity, central corneal thickness, and endothelial cell density before and 6 months after rejection were compared. RESULTS: Twenty of 377 eyes (5.3%) experienced an episode of stromal rejection [17/265 (6.4%) in group 1, 2/71 (2.8%) in group 2, and 1/41 (2.4%) in group 3]. The mean time interval between DALK and the rejection onset was 11.8 months (range 1-24). The cumulative probability of rejection episodes did not differ significantly among the 3 groups. All episodes resolved within 6 months after the onset, with no significant differences between prerejection and 6-month postrejection values of corrected distance visual acuity, central corneal thickness, and endothelial cell density. CONCLUSIONS: The rate of immunologic stromal rejection after large 9-mm DALK is within the range reported in the literature for conventional DALK, regardless of the indication for surgery.

Ultrasound Cyclo Plasty in Eyes with Glaucoma.

Glaucoma is a chronic disease caused by the progressive degeneration of the optical nerve fibers, resulting in decreased visual field that can lead to severe visual impairment, and eventually blindness. This manuscript describes a simple, surgeon-friendly, non-incisional technique, named Ultrasound Cyclo Plasty (UCP), for reducing intraocular pressure (IOP) in glaucoma patients. The technique determines a selective coagulation necrosis of the ciliary body; in addition, the stimulation of supra-choroidal and trans-scleral portions of the uveo-scleral outflow pathway has been recently proposed. UCP shows several technical improvements in ultrasound technology compared to previous techniques, providing more precise focusing on the target zone. The procedure is performed in the operating room under peribulbar anesthesia. Briefly, the coupling cone is put in contact with the eye and the ring probe, that contains six piezoelectric transducers which produce the ultrasound beams, is inserted inside it. Their proper centering over the ocular surface represents a crucial step for the correct targeting of the ciliary body. Sterile balanced salt solution is used to fill the empty spaces to ensure ultrasound acoustic propagation. Surgical treatment consists in the sequential automatic activation of each of the six transducers, for a total duration of less than 3 min. The patient leaves the hospital 1 h after the procedure with the treated eye patched. In the present study, 10 patients with open-angle glaucoma were followed-up during at least 12 months after the procedure. IOP was reduced at each interval compared to pre-operative, as well as the number of hypotensive medications. Twenty percent of patients did not respond to the treatment, and needed subsequent surgery to better control IOP. Treatment tolerability was good, with no cases of hypotony or phthisis. The UCP procedure is simpler, faster, safer, and less invasive than traditional cyclodestructive procedures with similar results in reducing IOP.

Predictive role of tear protein expression in the early diagnosis of Sjögren's syndrome.

Background The contribution of tear protein expression in patients with presumed diagnosis of Sjögren syndrome is underestimated. We aimed to evaluate the role of tear proteins in the Sjögren syndrome early diagnosis. Methods Charts from 110 patients suspected of Sjögren syndrome were analysed and the subsequent diagnosis retrieved. Subjective symptoms (ocular surface disease index, OSDI), tear film break-up time (TFBUT), Schirmer test, Jones test, tear clearance (TC), corneal (NEI score) and conjunctival staining (van Bjerstelveldt score), esthesiometry, cytology, tear protein analysis (total protein [TP] content, lysozyme-C [LYS-C], lactoferrin [LACTO], lipocalin-1 [LIPOC-1] and albumin [ALB]) were analysed. The diagnostic performance with area under the curve (AUC) and odds ratio (OR) for each parameter were calculated. Results Thirty-five patients (31.8%) had been diagnosed as affected by Sjögren syndrome. Clinical tests showed lower diagnostic performance (OSDI > 44 [AUC 0.57], Schirmer ≤ 5 mm [0.59], TFBUT ≤ 3 s [0.72], TC > 1/16 [0.68], Jones ≤ 4 mm [0.68], corneal staining > 2 [0.51], conjunctival staining > 2 [0.78]) compared with tear proteins (LYS-C ≤ 1.5 mg/mL [0.79], LACTO ≤ 20% [0.94], LIPOC-1 ≤ 10% [0.89], ALB ≥ 15% [0.79]). LYS-C, LACTO, LIPOC-1 and ALB showed a significant association in predicting Sjögren syndrome vs. not-Sjögren syndrome dry eye (OR, respectively, 4.9, 5.5, 7.2, 6.7). Conclusions Tear proteins' concentrations showed a significant higher accuracy compared with the traditional ocular clinical tests for reaching Sjögren syndrome's diagnosis. In particular, LACTO and LIPOC-1 provided an excellent diagnostic performance and thus could likely be considered promising biomarkers of Sjögren syndrome.