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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. Cho- roidal 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 mm2 vs. 0.491 ± 0.132, P = 0.006; 0.263 ± 0.152 mm2 vs. 0.340 ± 0.094, P = 0.002; 185.2 ± 79.8 mm vs. 216.8 ± 58.8 mm, P = 0.036, respectively). Best-corrected visual acuity was significantly correlated only with choroidal thickness (R = 20.509; P = 0.002). During the follow-up period in patients with GA, sub- foveal choroidal thickness decreased from 185.2 ± 79.8 to 152.2 ± 73.1 (P = 0.001), stromal area increased from 0.138 ± 0.090 mm2 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.

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

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.

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

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.

AimTo 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.MethodsThis 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 (pResultsCorneal 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.ConclusionsOverall, DED signs improved after both CBS and PBS treatments, with potential advantages of CBS for subjective symptoms and corneal damage reduction.Clinical trial registrationNCT03064984.

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 signif- icantly decreased at V2 compared with V1 (respectively, 20.4 6 7.9 vs. 17.4 6 10.1 n/mm2; 13.5 6 4.0 vs. 12.0 6 5.1 mm/mm2; 1.466 6 0.046 vs. 1.475 6 0.033; and 0.022 6 0.002 vs. 0.023 6 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 6 0.041 to 1.471 6 0.030 and from 1.479 6 0.050 to 1.481 6 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.

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.

Purpose A red eye is common in the ophthalmic practice, and redness is one out of four cardinal signs of inflammation. The correlation between the conjunctival bulbar redness (CBR) and ocular surface parameters, including tear cytokine levels, was investigated, in patients suffering from Dry Eye (DE). Methods Thirty five patients diagnosed as suffering from DE and fifteen age and sex matched healthy volunteers and were analyzed with respect to: 1. subjective symptoms of discomfort with the Ocular Surface Disease Index (OSDI ranging 0-100), and Visual Analogue Score (VAS, ranging 0-100 mm) ; 2.Tear Film Break Up Time (TFBUT, seconds); 3. Corneal vital and conjunctival vital staining scored by the NEI system (score 0-15, and 0-18, respectively); 4. Tear levels of exudated serum albumin (ALBU, mg/ml), and of the following Interleukins (IL): IL1b. IL-6. IL-17A. and Tumor Necrosis Factor (TNF)a (pg/ml), detected by the Luminex Technology Multiplex Assays; 5. the quantification of CBR analyzed on slit lamp digital images by using image processing of relative Red-channel activity with the free Image J software (NIH). Parameters were statistically analyzed in the two groups of subjects by using t-test and Mann-Whitney U test for parametric and nonparametric variables respectively. Relationship between variables was investigated using Spearman r correlation tests (significance p < 0.05). Results CBR was higher in DE as compared to controls (49.6 ± 3.5 vs 41.1 ± 2.4. p < 0.001). Tear IL-6 level was higher in DE patients vs controls (25.5 ± 15.5 vs 5.9 ± 3.1, p < 0.0001), whereas IL1b, IL-17A, and TNFa were detected in only the DE patients (median 5.73, 5.74, and 13.88 respectively) A significant correlation was found between CBR and IL-6 (r = 0.524), TNFa (0.571) TFBUT (-0.561), VAS score (0.832), and ALBU (0.628), p always

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.

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.

Purpose To describe a new objective technique of digital image analysis for the quantification and the morphological characterization of corneal staining in the setting of dry eye disease (DED), and to apply it to distinguish Sjögren syndrome (SS) from ocular graft versus-host disease (oGVHD). Methods Slit-lamp photographs of corneal staining obtained from 40 patients with DED (20 with SS and 20 with oGVHD; mean age 60.7 ± 12.3 years) were evaluated. Images were subjectively graded using Oxford and National Eye Institute (NEI) scales, the staining pattern was classified as micropunctate, macropunctate, coalescent, or patch. The corneal staining index (CSI) was calculated automatically using the software ImageJ 1.51s. Particles analysis was used to calculate mean area, circularity, and roundness of staining spots. Results CSI was significantly correlated with Oxford and NEI scales (respectively Rs = 0.823 and Rs = 0.773; both P < 0.001), and showed a good interobserver reliability (intraclass correlation coefficient [ICC] = 0.988 [95% confidence interval [CI]: 0.978–0.994]). The mean area of staining spots calculated with particles analysis was significantly correlated with the subjective classification of the staining pattern (Rs = 0.550, P < 0.001). The circularity and roundness of staining spots were significantly higher in oGVHD patients compared with SS (respectively, 0.51 ± 0.11 vs. 0.44 ± 0.10, P = 0.040; 0.61 ± 0.03 vs. 0.59 ± 0.02, P = 0.004). Sensitivity and specificity to distinguish oGVHD from SS were respectively 65.0% and 60% for circularity and 80.0% and 70.0% for roundness. Conclusions The new algorithm showed good reliability and was well correlated with the traditional subjective grading scales. Particles analysis for the objective assessment of the staining pattern may help to differentiate patients with oGVHD from those with SS. Translational Relevance The digital image analysis technique may be a reliable alternative to evaluate corneal staining objectively in the clinic and in clinical trials.

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 (β = 0.449; P = 0.003) and the history of previous chemotherapy (β = 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.