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Hintergrund: Mit der vorliegenden Studie sollte die Prävalenz von Symptomen des trockenen Auges bei Bauarbeitern im Vergleich zu Büroangestellten mithilfe des OSDI-Fragebogens untersucht werden. Methoden: Es wurde eine Querschnitts-Beobachtungsstudie durchgeführt, bei der die Symptome des trockenen Auges und die damit verbundenen Risikofaktoren anhand des OSDI-Fragebogens bewertet wurden. Die Berechnung der Stichprobengröße mit einer Power von 80 % und einem Konfidenzniveau von 95% ergab, dass 298 Teilnehmer in die Studie aufzunehmen waren. Ergebnisse: Wir untersuchten 304 Probanden (149 Bauarbeiter und 155 Büroangestellte). Mehr als die Hälfte (55%) der Teilnehmer zeigten Symptome des trockenen Auges (OSDI > 12). Der durchschnittliche OSDI-Score betrug 21,30 ± 22,20 Punkte und fiel in der Gruppe der Bauarbeiter (12,45 ± 17,50) niedriger aus als bei den Büroangestellten (28,51 ± 22,99) (p < 0,001). Bei Betrachtung der Teilnehmer mit mittelschweren und schweren Symptomen (23 bis 100 Punkte im OSDI) hatten Büroangestellte 4,15mal häufiger Symptome des trockenen Auges als Bauarbeiter (OR: 4,15, 95%-KI: 2,52, 6,85). Frauen wiesen statistisch höhere OSDI-Scores auf als Männer (32,47 ± 23,72 vs. 14.87 ± 18,48). Schlussfolgerungen: Bei Bauarbeitern ist das Risiko für Symptome des trockenen Auges viermal niedriger als bei Menschen, die in einer durchschnittlichen Büroumgebung arbeiten. Dies zeigt die schädlichen Effekte der Büroumgebung auf die Augenoberfläche, die ein erhebliches Risiko für die Entwicklung oder Verschlimmerung von Symptomen des trockenen Auges darstellen.

To validate the international chronic ocular graft-versus-host disease (GVHD) diagnostic criteria (ICCGVHD) compared to the National Institute of Health diagnostic criteria 2014 (NIH2014) for chronic ocular GVHD.Between 2013 and 2019, the study enrolled 233 patients with or without chronic ocular GVHD combined with the presence or absence of systemic chronic GVHD in an internationally prospective multicenter and observational cohort from 9 institutions. All patients were evaluated for four clinical parameters of ICCGVHD.The relation between the ICCGVHD score (0-11) and NIH2014 eye score (0-4) was relatively high (r = 0.708, 95% CI: 0.637-0.767, p 0.001). The sensitivity and specificity of ICCGVHD for NIH 2014 for 233 patients were 94.3% (95% CI: 89.6%-98.1%) and 71.7% (95% CI: 63.0-79.5%), respectively (cutoff value of the ICCGVHD score = 6). The positive predictive value was 77.1% (95% CI: 71.1%-82.1%), and the negative predictive value was 87.0% (95% CI:81.6-92.5%). For the patients with systemic GVHD (n = 171), the sensitivity and specificity were 94.2% and 67.2%, respectively (ICCGVHD-score cutoff value = 6). By receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.903 (95% CI: 0.859-0.948). For patients without systemic GVHD (n = 62), the sensitivity and specificity were 100% and 76.7%, respectively (ICCGVHD-score cutoff value = 6). The AUC was 0.891 (95% CI 0.673-1.000).Good sensitivity, specificity, predictive value and correlation were found between ICCGVHD and NIH2014. ICCGVHD scores ≥6 can be useful to diagnose ocular GVHD with or without systemic GVHD for clinical research.

Purpose Pilot study to evaluate the safety and efficacy of oral guaifenesin in reducing the signs and symptoms of filamentary keratitis. Methods Prospective, uncontrolled open-label pilot study. Twelve patients with non-Sjogren dry eye disease (DED) and secondary filamentary keratitis received treatment with oral guaifenesin 600 mg twice a day (total dose of 1.2 g/day) for 4 weeks. Adverse events, change in the number of corneal filaments, corneal fluorescein staining (CFS; NEI grading system), and symptoms (Ocular Surface Disease Index) were assessed. Results Before starting oral guaifenesin, all patients were on topical medical therapy for their condition. At baseline, the mean number of filaments was 5.8 ± 2.9, CFS score 7.3 ± 3.2, and OSDI score 55.6 ± 25. After 4 weeks of treatment, the number of filaments was 2.1 ± 2.2 (p = 0.04 vs. baseline), CFS score 6.5 ± 3.1 (p = 0.5), and OSDI score 46.1 ± 30.9 (p = 0.2). One patient discontinued the medication due to gastrointestinal side effects. Conclusions Oral guaifenesin was safe and generally well tolerated, and demonstrated modest efficacy in reducing the severity of filamentary keratitis. These results should be considered preliminary; however, placebo-controlled investigations would be justified to evaluate the therapeutic efficacy of oral guaifenesin as a mucolytic in treatment of filamentary keratitis.

Many recent studies have demonstrated that morphological changes are one of the key signs of Meibomian gland disease (MGD) . These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, Until now, there is no conclusive information about the impact of MG morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evapo-rative DED and healthy controls. Retrospective chart review of Seventy-five patients with evaporative dry eye and healthy individuals who had dry eye assesments included Ocular Surface Disease Index questionnaire, Meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and Meibography. We did not find significant differences in MG alterations in the upper lid between healthy and dry-eye subjects. Patients with evaporative dry eye presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs 30.3%; p=0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p

Background: To know the influence of coagulation time on the concentration of epitheliotropic factors of autologous serum.Methods: A prospective, cross-sectional and experimental study was conducted evaluating the concentrations of epitheliotropic factors in the serum of 20 healthy volunteers over 18 years of age, who did not suffer from diseases or took any medication or with a history of blood transfusion in the last year, those with diagnosis of anemia, coagulation diseases or another situation that contraindicates the sampling were excluded. Epidermal growth factor (EGF), Transforming growth factor β1 (TGF-β1) and Fibronectin were quantified in the various undiluted serum samples by an enzyme-linked immunosorbent assay.Results: 65% were male with an average age of 22.7 ± 5.47 years (range 19 to 45 years). Age was similar in both groups (p = 0.87), men had an average age of 22.85 ± 6.84 years and women 22.43 ± 1.13 years. Vitamin A and Fibronectin did not have a statistically significant difference of concentration at 2 and 24 hours, while the concentration of TGF-β1 had a statistically significant decrease as the clot formation time increased (average 0.22 range, 0.003,0.451), opposite, the EGF increased its concentration statistically significantly with the longer coagulation time (average -0.39 range, -0.60, -0.18).Conclusions: a prolonged clotting time (24 hours) have a significant impact on the composition and epitheliotrophic factors of the serum, increasing the EGF concentrations, and lowering the TGF-β1.

Background To investigate and contrast the prevalence of dry eye symptoms in construction workers and office workers using the OSDI questionnaire. Methods A cross-sectional, observational study was conducted using the OSDI questionnaire to evaluate dry eye symptoms and associated risk factors. Sampled size calculation with a power of 80% and a 95% degree of confidence suggested the inclusion of 298 participants. Results We studied 304 subjects (149 construction workers and 155 office workers). More than half (55%) of the participants presented dry eye symptoms (OSDI > 12). The average OSDI score was 21.30 ± 22.20 points, being lower in the group of construction workers (12.45 ± 17.50) than in-office workers (28.51 ± 22.99) (p Conclusions construction workers have four times less risk of presenting dry eye symptoms than people working in the average office space. This highlights the pernicious effects on the ocular surface of the office environment, which poses a significant risk for the development or worsening of dry eye symptoms.

We report the surgical management of a patient with bilateral anterior lenticonus due to Alport syndrome using femtosecond laser-assisted cataract surgery (FLACS) and the Optiwave Refractive Analysis (ORA) system. A 38-year-old man with Alport syndrome presented to our department with visual loss due to anterior lenticonus in both eyes. Adjustments during bilateral FLACS were performed with the software’s calipers to manually delineate the anterior capsulotomy. Multifocal toric intraocular lenses (IOLs) were selected and placed in the posterior chamber with the aid of intraoperative aberrometry. The intended postoperative positioning parameters for the IOL as well as the planned visual acuity and refraction were achieved. The implementation of FLACS and intraoperative wavefront aberrometry is a safe and useful surgical approach for the management of cataract in challenging cases such as patients with anterior lenticonus due to Alport syndrome.

Purpose To investigate the feasibility of remote assessment and follow-up of dry eye symptoms using electronic versions of two validated questionnaires. Methods We conducted a prospective study of consecutive patients with dry eye disease (DED). Patients were enrolled during a clinical visit and were explained how to respond electronic versions of the Ocular surface Disease Index (OSDI) and the Symptom Assessment in Dry Eye (SANDE) questionnaires using a computer in the presence of investigators. A secure link to both questionnaires was sent to each patient every 2 weeks in order to respond and submit their symptoms over a 3-month period. We analyzed the number of patients who responded to both questionnaires, the recurrence, and the symptoms scores reported. Results A total of 1121 questionnaires were collected; 103 patients (85%) reported their symptoms at least once during the 3-month study duration. The majority of participants who completed the study (71.6%) responded remotely at least once per month during the 3-month duration of the study. The mean OSDI and SANDE scores from the total of remote evaluations were 34.9 ± 21.9 (range 0–97.5) and 50.3 ± 24.9 (range 0–100), respectively. There was a statistically significant correlation between the total scores collected with the two questionnaires (R = 0.67, P Conclusions Patients are motivated to report DED symptoms while away from the clinic. Distance-based evaluation of DED symptoms is both feasible and convenient, and can be implemented to follow symptoms in large populations with chronic dry eye.

Purpose To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Design Phase 1/2 prospective, randomized, double-masked clinical trial. Participants Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled. Methods Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen. Main Outcome Measures Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). Results After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups ( P = 0.06). However, burning sensation was more pronounced with tacrolimus ( P = 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P = 0.01) and achieved significant improvement in TBUT when compared with baseline ( P P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group ( P = 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 ( P = 0.04). Conclusions Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids.

To evaluate the prevalence of ocular hypertension (OHT) and glaucoma in patients with chronic ocular graft-versus-host disease (GVHD).We performed a retrospective chart review of 218 patients diagnosed with chronic ocular GVHD. Ocular hypertension was defined as intraocular pressure (IOP) ≥ 24 mmHg in either eye without any glaucomatous optic disc changes. Glaucoma suspect was defined as optic disc changes with a cup-to-disc ratio ≥ 0.7 in either eye or asymmetry of ≥ 0.3 between the two eyes. Glaucoma was defined by glaucomatous optic disc changes plus glaucomatous visual field defects in two consecutive reliable visual field tests. The number of cases of ocular hypertension, glaucoma, and glaucoma suspects was evaluated.Thirty-three patients (15 %) were diagnosed with OHT, eight patients (3.6 %) with suspicion of glaucoma, and one patient (0.4 %) with glaucoma. OHT occurred within 6 months of developing ocular GVHD in 60 % of the cases and within the first year in 76 %. High IOP normalized in 67 % of patients when the dosage of topical or systemic corticosteroids was lowered, and 27 % of patients required anti-glaucoma therapy.Ocular hypertension is a common complication in patients with ocular GVHD, with a prevalence of 15 %. The rise in intraocular pressure is often transient and resolves with management of corticosteroids in most cases. However, clinicians should be aware that nearly one-third of the patients with OHT might require anti-glaucoma treatment. The prevalences of glaucoma and suspicion of glaucoma were not higher than in the general population.

Purpose To present the process of cultural and psychometric adaptation, and clinical validation of a new version in the Spanish language of the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8). Materials and methods The translation-retro-translation method was applied to the CLDEQ-8 questionnaire. Two independent native Spanish-speaking translators adapted the questionnaire from English to Spanish, and then a committee of experienced clinicians (CE) evaluated the semantic equivalence and designed a Spanish version of the CLDEQ-8 questionnaire. The resulting translated version was tested conducting a pilot study in contact lens users and assessing their perception and overall understanding of the terminology. The results were analyzed and a final version was designed. The final version was retro-translated to English by a native English-speaking translator and compared with the original CLDEQ-8 version to confirm there were no meaningful differences. To clinically validate the new instrument, a prospective study was conducted to apply the new Spanish CLDEQ-8 to 50 contact lens users. Results Fifty patients were studied with an average age of 21.50 ± 1.66 years. The average CLDEQ-8 score was 13.28 ± 6.81 points (range 1–31). The internal consistency (Cronbach's alpha) was 0.89, with a corrected index of homogeneity >0.50 for all evaluated items. Conclusions The process of trans-cultural adaptation of the questionnaire CLDEQ-8 resulted in the elaboration of a reliable and much needed instrument capable of measuring frequency and intensity of dry eye symptoms in Spanish-speaking contact lens users.

Purpose To assess the vision-related quality of life (QOL) in a cohort of patients with ocular graft-versus-host disease (GVHD). Design Prospective study. Participants Eighty-four patients diagnosed with chronic ocular GVHD. Methods We assessed the vision-related QOL with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires. Main Outcome Measures We assessed vision-related QOL with the NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD with those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and the dry eye symptoms measured by the OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time, and Schirmer test. Results The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5±17. Compared with healthy subjects, patients with ocular GVHD reported reduced scores on all NEI-VFQ-25 subscales (each P P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI ( R = −0.81, P R = −0.56, P R = −0.36, P = 0.001), and BCVA ( R = −0.30, P = 0.004). Conclusions Patients with ocular GVHD experience measurable impairment of vision-related QOL. This study highlights the impact of ocular GVHD on the vision-related QOL, and thus the importance of comprehensive diagnosis and treatment of this condition.

Purpose The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) as assessed by the Ocular Surface Disease Index (OSDI), a 12-item symptom frequency–based questionnaire, and the Symptom Assessment iN Dry Eye (SANDE), a 2-item frequency- and severity-based visual analog scale. Design Clinic-based evaluation of a diagnostic test. Participants A total of 114 patients with DED. Methods Patients were administered the OSDI and SANDE questionnaires at baseline and follow-up visits to evaluate DED-related symptoms. The correlations between both questionnaires' scores were evaluated using the Spearman coefficient, and their clinical differences were assessed using Bland–Altman analysis. Main Outcome Measures Baseline and follow-up visit OSDI and SANDE dry eye symptom scores. Results At the baseline visit, the OSDI and SANDE questionnaire scores were significantly correlated ( R = 0.64; P R = 0.47; P Conclusions Data collected from the SANDE questionnaire showed a significant correlation and negligible score differences with those from the OSDI, suggesting that the SANDE visual analog scale–based questionnaire has the potential to provide clinicians with a short, quick, and reliable measure for DED symptoms.

To study the factors affecting the time to onset of ocular graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).A retrospective chart review of 200 patients with ocular GVHD was performed to evaluate the association between various donor-recipient characteristics and the time to onset of ocular GVHD after allo-HSCT.The median time to onset of chronic ocular GVHD after allo-HSCT was 293 days (range, 26-2308 days). Patients receiving fully human leukocyte antigen (HLA)-matched transplants had a delayed onset of ocular GVHD (median, 294 days) compared with mismatched transplants (219 days; P = 0.029). HLA-matched transplants from related donors had delayed onset of ocular GVHD (307 days) compared with HLA-matched (286 days; P = 0.168) and HLA-mismatched (231 days; P = 0.015) transplants from unrelated donors. Ocular GVHD followed systemic GVHD in 76% of patients but preceded systemic disease in 7%, occurred concurrently in 15%, and was not associated with systemic GVHD in 2% of patients. The time elapsed between the occurrence of systemic and ocular GVHD was significantly longer in matched-related transplants (250 days) than in matched-unrelated transplants (120 days; P = 0.004).The onset of ocular GVHD after allo-HSCT is variable and is influenced by donor-recipient matching characteristics. In the majority of patients with GVHD, ocular involvement follows the occurrence of systemic manifestations; however, importantly, it can also precede or develop independently of systemic disease in a minority of patients. Regular ophthalmic follow-up is recommended after allo-HSCT regardless of concurrent systemic GVHD status.

PURPOSE To evaluate interobserver concordance in measured ocular redness among a group of raters using an objective computer-assisted method (ocular redness index [ORI]) and a group of clinicians using an ordinal comparative scale. METHODS We conducted a prospective study to evaluate ocular redness in clinical photographs of 12 patients undergoing pterygium surgery. Photographs were acquired preoperatively, and at 1 week and 1 month postoperatively. One group of clinicians graded conjunctival redness in the photographs using an image-based comparative scale. A second group applied the ORI to measure redness in the same photographs. We evaluated redness change between time points, level of agreement among raters, and assessed redness score differences among observers within each group. RESULTS Interobserver agreement using the image-based redness scale was 0.458 (P < 0.001). Interobserver agreement with the ORI was 0.997 (P < 0.001). We observed statistically significant differences among clinicians' measurements obtained with the image-based redness scale (P < 0.001). There were no significant differences among measurements obtained with the ORI (P = 0.27). We observed a significant change in redness between baseline and follow-up visits with all scoring methods. Detailed analysis of redness change was performed only in the ORI group due to availability of continuous scores. CONCLUSION Our findings suggest that the ORI scores provide higher consistency among raters than ordinal scales, and can discriminate redness changes that clinical observers often can miss. TRANSLATIONAL RELEVANCE The ORI may be a reliable alternative to measure ocular redness objectively in the clinic and in clinical trials.

Dry eye disease is a multifactorial, complex and chronic disease that entails an important inflammatory component. The prevalence of this condition continues to increase, with the potential to significantly reduce patients’ quality of life. Treatment options are limited, and thus new treatment options are continuously being investigated in the laboratory and in the clinic. IL-1 receptor antagonist is a targeted biologic that blocks the binding of IL-1α and IL-1β to their signaling receptor IL-1R1, thereby nullifying their inflammatory function. Treatment with topical IL-1 receptor antagonist has been shown to reduce inflammation in experimental dry eye in mice. Recently, a prospective, randomized, double-masked, vehicle-controlled clinical trial confirmed the previous preclinical results, and showed that topical application of IL-1 receptor antagonist significantly reduces corneal epitheliopathy and symptoms of discomfort in patients with dry eye disease.

PURPOSE To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). METHODS This was a prospective, open-label, monocentric, uncontrolled noncomparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up period of 16 weeks. The main corneal NV outcome measures were: neovascular area, the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA. RESULTS Statistically significant decreases in neovascular area (55.3%, P < 0.001), which lasted through 16 weeks, and VC (59%, P < 0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P = 0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. CONCLUSIONS Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA.

To investigate the levels of neutrophil elastase (NE), matrix metalloproteinases (MMPs), and myeloperoxidase (MPO) in tear washes of patients with ocular graft-vs-host disease (oGVHD).Case-control study.Based on established criteria, oGVHD patients (n = 14; 28 eyes) and age-/sex-matched healthy controls (n = 14; 28 eyes) were enrolled. Tear washes were collected and analyzed for NE using a single-analyte enzyme-linked immunosorbent assay (ELISA). MMPs (1, 2, 3, 7, 8, 9, 12), MPO, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were analyzed using multianalyte bead-based ELISA assays. Total MMP activity was measured using a fluorimetric assay. Correlation studies were performed between NE, MMP-8, MMP-9, and MPO within study groups.NE, MMP-8, MMP-9, and MPO levels were elevated in oGVHD tears when compared with controls (P.0001). NE was the most elevated analyte. MMP activity was higher and TIMP-1 levels were lower in oGVHD than in control (P.0001). In oGVHD, NE significantly correlated with MMP-8 (r = 0.92), MMP-9 (r = 0.90), and MPO (r = 0.79) (P.0001). MMP-8 correlated with MMP-9 (r = 0.96, P.0001), and MPO (r = 0.60, P = .001). MMP-9 correlated with MPO (r = 0.55, P = .002). In controls, NE, MMP-9, and MPO significantly correlated with each other (P.0001).The marked increase in NE in oGVHD tears that correlated strongly with elevated MMP-8, MMP-9, and MPO suggests a common neutrophilic source and provides evidence of neutrophil activity on the ocular surface of oGVHD patients.

To compare the surgical duration and clinical outcomes of nasolacrimal recanalization versus external dacryocystorhinostomy (DCR) in the treatment of failed nasolacrimal duct intubation. This is a retrospective, comparative, and interventional study. We evaluated the outcomes of 66 consecutive patients undergoing either nasolacrimal recanalization (n = 32) or DCR (n = 34) in a tertiary lacrimal disease referral center. Length of surgical duration, clinical outcomes, and rate of recurrence at 18 months postoperatively were compared. The mean surgical duration was 18.5 minutes (range, 15–25 minutes) for nasolacrimal recanalization and 48.2 minutes (range, 45–61 minutes) for DCR, respectively (P

PURPOSE: To measure the refractive index (RI) of the human corneal stroma in vivo using an objective Abbe refractometer (VCH-1) and to determine if RI of the stroma is related to age. METHODS: VCH-1 was used to measure RI at the central anterior stroma immediately after lifting the flap in neophyte patients preselected for laser in situ keratomileusis. Surgical procedures continued as preplanned after measuring the RI, and in binocular cases, measurements were taken from the right eye only. Corneal flaps were created using a femtosecond laser system. RESULTS: Mean RI (±SD, range) and age (±SD, range) values were 1.373 (±0.006, 1.358-1.385) and 36.55 (±12.26, 18-74). A significant linear correlation was found between age and RI. Least squares regression lines equating RI with age (x, years) were of the form: RI = 1.36911 + 0.000096x (r = +0.195; n = 115; P = 0.037). Mean RI (± SD) in the 2 age groups separated by the median age (≤34 and ≥35) were 1.371 (±0.007; n = 57) and 1.374 (±0.005; n = 58). The difference was statistically significant (P = 0.018). CONCLUSIONS: RI of the anterior stroma in vivo tends to be increased in older patients when the corneal flap is created using a femtosecond laser device.

PURPOSE: To compare the visual acuity outcomes as well as the ocular optical performance of eyes implanted with either a monofocal or one of two diffractive multifocal intraocular lenses (IOLs). METHODS: One hundred two consecutive eyes of 51 bilateral cataract patients (age 49 to 80 years) were divided into three groups: 22 eyes were implanted with a monofocal IOL (monofocal group), 40 eyes with the Acrysof ReSTOR SN6AD3 IOL (ReSTOR group), and 40 eyes with the Acri.Lisa 366D IOL (Acri.Lisa group). Visual acuity and contrast sensitivity were evaluated pre- and postoperatively. Additionally, ocular optical quality and intraocular aberrations were evaluated postoperatively. RESULTS: Significant improvement after surgery in uncorrected and corrected distance and near visual acuity was observed in all three groups ( P ≤.05). Uncorrected near visual acuity was significantly better in eyes from the ReSTOR and Acri.Lisa groups compared to the monofocal group ( P ≤.01). Photopic contrast sensitivity was significantly better for the spatial frequency of 3 cycles/degree in the monofocal group ( P P =.01). An acceptable range of vision between near and distance peaks was observed in the defocus curves of the ReSTOR and Acri.Lisa groups. CONCLUSIONS: The AcrySof ReSTOR and Acri.Lisa 366D IOLs are able to successfully restore near and intermediate visual function after cataract surgery; however, the Acri.Lisa design seems to provide better optical performance. These results need to be confirmed in a randomized, prospective trial.

Purpose To evaluate the intraobserver repeatability of pachymetric measurements obtained with a new Scheimpflug photography–based system and the agreement of the measurements with those obtained by optical coherence tomography (OCT). Setting Vissum Corporation, Alicante, Spain. Design Evaluation of diagnostic technology. Methods Corneal thickness was measured at different locations (center; 2.5 mm and 4.0 mm nasal, temporal, superior, and inferior) in 18 eyes of 18 patients with no ocular pathology or previous surgery with a Scheimpflug photography–based system (Sirius). Three consecutive measurements at each location were obtained with the system to evaluate intraobserver repeatability. Afterward, pachymetric measurements were obtained at the same locations with an OCT system (Visante) to evaluate the agreement between techniques using the Bland-Altman method. Results The intraclass correlation coefficient of repeated measures ranged from 0.990 to 0.997. The coefficient of variation was lower than 1% and the standard deviations of the repeated measurements (S w ) were below 6 μm at all corneal locations. Statistically significant differences were found between the coefficient of variation and S w values of the repeated measurements corresponding to the 2.5 mm and 4.0 mm locations ( P ≤.037). The agreement with OCT pachymetric measurements was poor, with ranges of agreement larger than 20 μm at all corneal locations. Statistically significant differences were found between standard deviations of the differences between the 2 devices at the 2.5 mm and 4.0 mm locations ( P ≤.017). Conclusion Scheimpflug photography–based technology provided repeatable pachymetric measurements that were not equivalent to those obtained with OCT. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

To evaluate the reading performance, changes in quality of life, and optical performance after cataract surgery with multifocal diffractive intraocular lens (IOL) implantation.Vissum Corporation, Alicante, Spain.Prospective case series.Patients with bilateral cataract had implantation of Acri.LISA 366D multifocal IOLs. Visual acuity and contrast sensitivity outcomes were evaluated during a 6-month follow-up. Other parameters evaluated included reading performance (Salzburg Reading Desk), a 25-item quality-of-life questionnaire (National Eye Institute Visual Functioning Questionnaire-25 [NEI VFQ-25] and appendix NEI VFQ-39), and ocular optical performance (ocular aberrometry and modulation transfer function).The study included 48 eyes (24 patients) ranging in age from 47 to 77 years. The mean uncorrected distance visual acuity (logMAR) improved significantly 1 month postoperatively (P.01), with no significant changes afterward (6 months, P≥.06). The mean reading acuity without correction improved significantly from 0.68 logRAD ± 0.20 (SD) to 0.16 ± 0.08 logRAD 1 month after surgery (P.01). However, it was worse by the end of the follow-up (6 months, P = .04). During the follow-up, no significant changes were found in the mean reading speed without near correction (6 months, P = .50). Contrast sensitivity improved significantly at all spatial frequencies under photopic and scotopic conditions after surgery (6 months, P≤.02). The quality-of-life index related to reading ability also improved significantly (3 months, P = .03).Implantation of the multifocal diffractive IOL significantly improved reading performance, which had a positive effect on the patient's quality of life postoperatively.No author has a financial or proprietary interest in any material or method mentioned.

To determine the factors affecting corneal biomechanics using biomechanical waveform analysis after microincision cataract surgery (MICS) and standard coaxial phacoemulsification with different incision sizes.Vissum-Instituto Oftalmologico de Alicante, Alicante, Spain.This prospective nonrandomized study comprised eyes with significant cataract that had MICS (sub-1.8 mm incision) or coaxial phacoemulsification (2.75 mm incision). Corneal hysteresis (CH) and the corneal resistance factor (CRF) were measured by biomechanical waveform analysis (Ocular Response Analyzer) preoperatively, immediately postoperatively, and at 1 month. Results were analyzed and compared between groups.In the MICS group (n = 30), there was a significant increase in Goldmann-correlated intraocular pressure (IOP) and corneal-compensated IOP, although CH decreased in the immediate postoperative period (P.05). At 1 month, all parameters in the MICS group returned to normal. The coaxial group (n = 30) had an increase in Goldmann-correlated IOP and corneal-compensated IOP, both of which were higher than normal at 1 month. Backward multiple regression analysis showed significant correlations between CH and preoperative Goldmann-correlated IOP and preoperative CRF (r(2) = 0.631, P.05); between age, axial length (AL), and preoperative CRF (r(2) = 0.418, P.05); and between the change in CH and AL, total incision length, and preoperative CH (r(2) = 0.429, P.05).Cataract surgery with MICS and coaxial phacoemulsification significantly altered corneal biomechanics. Corneal hysteresis was inversely correlated with Goldmann-correlated IOP; CRF was inversely correlated with age and AL. The MICS technique provided more stable corneal biomechanical properties than standard coaxial phacoemulsification 1 month postoperatively.

To investigate the expression, release, and proteolytic degradation of galectin-3 in patients with dry eye disease.Observational case series with a comparison group.Tear washes and conjunctival impression cytology specimens were collected through standard procedures from 16 patients with dry eye and 11 age-matched healthy subjects. Galectin-3 content in tears was analyzed by quantitative Western blot, using recombinant galectin-3 protein to generate a calibration curve. The relative expression of galectin-3 and matrix metalloproteinase 9 (MMP9) was evaluated by quantitative polymerase chain reaction. The cleavage of galectin-3 was studied in vitro using activated recombinant MMP9 and protease inhibitors.The concentration of galectin-3 protein in tears, but not galectin-3 expression in conjunctival epithelium, was significantly higher in tears of patients with dry eye (0.38 ng/μg total protein, range 0.04-1.36) compared to healthy subjects (0.12 ng/μg total protein, range 0.00-0.41) (P.01). By Western blot, an intact (∼28.0 kDa) galectin-3 band was identified in tear samples from healthy subjects, whereas 50% of the dry eye samples were characterized by the additional presence of a partially degraded form (∼25.4 kDa). In our experiments, elevated expression of MMP9 in dry eye subjects correlated with the ability of active MMP9 to cleave galectin-3 from recombinant origin. Interestingly, cleavage of endogenous galectin-3 in tear samples was impaired using a broad-spectrum proteinase inhibitor cocktail, but not the pan-specific MMP inhibitor GM6001, suggesting the presence of proteases other than MMPs in promoting galectin-3 degradation in dry eye.Our results indicate that release of cellular galectin-3 into tears is associated with epithelial dysfunction in dry eye, and that galectin-3 proteolytic cleavage may contribute to impaired ocular surface barrier function.

Purpose To evaluate interobserver concordance in measured corneal fluorescein staining (CFS) using the National Eye Institute/Industry (NEI) grading scale and the Corneal Fluorescein Staining Index (CFSi), a computer-assisted, objective, centesimal scoring system. Methods We conducted a study to evaluate CFS in clinical photographs of patients with corneal epitheliopathy. One group of clinicians graded CFS in the images using the NEI while a second group applied the CFSi. We evaluated the level of interobserver agreement and differences among CFS scores with each method, level of correlation between the two methods, and distribution of cases based on the CFS severity assigned by each method. Results The level of interobserver agreement was 0.65 (P < 0.001) with the NEI, and 0.99 (P < 0.001) with the CFSi. There were statistically significant differences among clinicians' measurements obtained with the NEI (P < 0.001), but not with the CFSi (P = 0.78). There was a statistically significant correlation between the CFS scores obtained with the two methods (R = 0.72; P < 0.001). The NEI scale allocated the majority of cases (65%) within the higher quartile in the scale's severity (12-15/15). In contrast, the CFSi allocated the majority of cases (61%) within the lower quartile in the scale's severity (0-25/100). Conclusions The CFSi is easy to implement, provides higher interobserver consistency, and due to its continuous score can discriminate smaller differences in CFS. Reproducibility of the computer-based system is higher and, interestingly, the system allocates cases of epitheliopathy in different severity categories than clinicians do. The CFSi can be an alternative for objective CFS evaluation in the clinic and in clinical trials.

To evaluate whether levels of corneal subbasal nerve fiber length (SNFL) in dry eye disease (DED) could prognosticate the level of improvement in signs and symptoms after treatment.Phase IV, double-masked, randomized clinical trial.Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls.Patients with DED were randomized to receive topical artificial tears, loteprednol etabonate 0.5%, or loteprednol etabonate 0.5%/tobramycin 0.3% twice daily for 4 weeks. At baseline, in vivo confocal microscopy of central cornea was performed in both eyes. Patients with DED were divided into 2 subgroups: those with low baseline SNFL and those with near-normal baseline SNFL for this purpose (the cutoff point: the mean SNFL in controls minus 2 standard deviations). Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups.Symptom questionnaires, corneal fluorescein staining (CFS), conjunctival staining with lissamine green, tear break-up time, Schirmer's test, and SNFL.In patients with DED, baseline SNFL (17.06±5.78 mm/mm(2)) was significantly lower than in controls (23.68±3.42 mm/mm(2), P = 0.001). In the artificial tear and loteprednol groups, although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL (16.84 mm/mm(2)), subjects with near-normal baseline SNFL (≥16.84 mm/mm(2)) showed significant improvement in both symptoms and CFS score (all P0.05). In the loteprednol/tobramycin group, no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL.Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL. Consideration of SNFL may assist in explaining the variability of patients' response to DED therapy.

William Stevenson, Hasanain Shikari, Ujwala S Saboo, Francisco Amparo, Reza Dana Cornea Service, Massachusetts Eye and Ear Infirmary, Boston, MA, USA Purpose: To report on corneal ulceration in ocular graft-versus-host disease (GVHD). Methods: This was a retrospective, observational case series investigating corneal ulceration and perforation in a cohort of ocular GVHD patients seen between June 2007 and October 2012. Results: Four of 243 ocular GVHD patients developed corneal ulcerations attributable to ocular GVHD, and all four cases involved bilateral corneal ulceration. The median length of time from the diagnosis of ocular GVHD to the diagnosis of the first corneal ulceration was 317 days (range 168–434). The median length of time between the diagnosis of corneal ulceration in each patient's first and second eye was 248 days (range 9–645). Outcomes varied from complete resolution with medical treatment to corneal perforation necessitating penetrating keratoplasty. In cases of corneal perforation, the median length of time from the diagnosis of corneal ulceration to perforation was 10 days (range 0–20). Common clinical features included: centrally or paracentrally located ulcerations and perforations, concomitant dry eye, and the use of topical or systemic corticosteroids. Conclusion: Frequent follow-up and bilateral monitoring are highly recommended in cases of ocular GVHD-associated stromal thinning, as bilateral involvement or rapid progression to corneal perforation can occur. Keywords: graft-versus-host disease, ocular graft-versus-host disease, corneal ulceration, corneal perforation

To evaluate the correlation between changes in tear osmolarity, symptoms, and corneal fluorescein staining in patients with dry eye disease (DED).Retrospective, clinic-based cohort study.In this single-institution study, we reviewed the charts of 186 patients with DED from whom we had data on tear osmolarity, symptoms, and corneal fluorescein staining from 2 separate visits. Main outcomes included the correlation of the changes between the 2 visits for tear osmolarity (TearLab system), symptoms (Ocular Surface Disease Index), and corneal fluorescein staining (modified Oxford scheme). For tear osmolarity and corneal fluorescein staining the scores from the eye with highest readings were analyzed. The correlations were repeated on subgroups based on proposed cutoffs for DED severity and on patients' treatment.We found a modest, though statistically significant, correlation between changes in corneal fluorescein staining and symptoms of DED (R = 0.31; P.001). However, there was no correlation between the recorded change in tear osmolarity and symptoms (R = -0.091; P = .38) or between changes in tear osmolarity and corneal fluorescein staining (R = -0.02; P = .80). This lack of correlation was consistent in all the subgroups studied. A multivariate analysis revealed that changes in corneal fluorescein staining had predictive value on symptom changes, whereas tear osmolarity changes did not.Changes in tear osmolarity do not correlate significantly with changes in patient symptoms or corneal fluorescein staining in dry eye disease.

To develop and validate a novel automated system to assess ocular redness (OR) in clinical images.We developed a novel software that quantifies OR in digital images based on a mathematic algorithm using a centesimal continuous scoring scale. Subsequently, we conducted a study to validate the scores obtained with this system by correlating them with those obtained by two physicians using two image-based comparative subjective scales, the Efron and the Validated Bulbar Redness (VBR) grading scales. Additionally, we evaluated the level of clinical agreement between the Ocular Redness Index (ORI) score and the two image-based methods by means of the Bland-Altman analysis. Main outcome measures included correlation and level of agreement between the ORI score, Efron score, and the VBR score.One hundred and two clinical photographs of eyes with OR were evaluated. The ORI scores significantly correlated with the scores obtained by the two clinicians using the Efron (Observer 1, R=0.925, P0.001; Observer 2, R=0.857, P0.001), and VBR (Observer 1, R=0.830, P0.001; Observer 2, R=0.821, P0.001) scales. The Bland-Altman analysis revealed levels of disagreement of up to 30 and 27 units for the ORI-Efron and ORI-VBR score comparisons, respectively.The ORI provides an objective and continuous scale for evaluating ocular injection in an automated manner, and without need for a trained physician for scoring. The ORI may be used as a new alternative for objective OR evaluation in clinics and in clinical trials.

The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy.To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction.Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial.Seventy-five patients with refractory DED.Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks.Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality.Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P.001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms.Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681109.

Purpose To determine the influence of age and the corneal stromal refractive index on the difference between the predicted and actual postoperative refractive error after laser in situ keratomileusis (LASIK) and whether the precision of outcomes could be improved by considering age and the refractive index. setting Vissum Instituto Oftalmologico de Alicante, Alicante, Spain. Design Case series. Methods Flaps were created using a mechanical microkeratome. The stromal refractive index was measured using a VCH-1 refractometer after flap lifting. Refractive data were obtained 1, 3, and 6 months postoperatively. Results Uneventful LASIK was performed in 133 eyes. The mean age, refractive index, and applied corrections were 33.4 years ± 9.49 (SD), 1.368 ± 0.006, and −2.43 ± 3.36 diopters (D), respectively. The difference between the predicted and actual postoperative refractive error = 2.315−0.021 age−1.106 refractive index (F = 3.647, r = 0.254, P=.029; n = 109) at 1 month and = 11.820−0.023 age−7.976 refractive index (F = 3.392, r = 0.261, P=.022, n = 106) at 3 months. A correlation between the actual and calculated postoperative refraction improved from r = −0.178 (P=.064; n = 75) to r = −0.418 (P Conclusions The predicted outcomes of LASIK can be improved by inputting the refractive index of the individual corneal stroma. Unexpected outcomes (>0.50 D) of LASIK could be avoided by considering patient age and the refractive index and by adjusting the applied correction accordingly. Financial Disclosure Drs. Patel and Alio have a propriety interest in the VCH-1 refractometer used in this study. Both authors consulted on the design of the device by the manufacturers.

To determine the effect of phosphodiesterase type-4 (PDE4) inhibition on IL-17-associated immunity in experimental dry eye disease (DED).Murine DED was induced, after which a PDE4 inhibitor (cilomilast), dexamethasone, cyclosporine, or a relevant vehicle was administered topically. Real-time PCR, immunohistochemical staining, and flow cytometry were employed to evaluate the immuno-inflammatory parameters of DED with a focus on IL-17-associated immunity. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease progression.DED induction increased proinflammatory cytokine expression, pathogenic immune cell infiltration, and CFS scores. Cilomilast significantly decreased the expression of TNF-α in the cornea (P ≤ 0.05) and IL-1α, IL-1β, and TNF-α in the conjunctiva (P ≤ 0.05) as compared with vehicle control. Cilomilast treatment markedly decreased the presence of CD11b+ antigen-presenting cells in the central and peripheral cornea (P ≤ 0.05), and led to decreased conjunctival expression of cytokines IL-6, IL-23, and IL-17 (P ≤ 0.05). Moreover, cilomilast decreased the expression of IL-17 and IL-23 in the draining lymph nodes (P ≤ 0.05). Topical cilomilast was significantly more effective than vehicle at reducing CFS scores (P ≤ 0.05). The therapeutic efficacy of cilomilast was comparable or superior to that of dexamethasone and cyclosporine in all tested measures.Topical cilomilast suppresses the generation of IL-17-associated immunity in experimental DED.

To compare vision-related quality of life using the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in patients with 1 of 3 types of intraocular lenses (IOLs) and to correlate it with postoperative visual outcomes.Vissum Corporation-Instituto Oftalmológico de Alicante, Alicante, Spain.Comparative case series.This study comprised eyes having cataract surgery with bilateral implantation of a monofocal IOL (Group A), apodized multifocal IOL (Group B), or full diffractive multifocal IOL (Group C). Distance and near visual acuities, contrast sensitivity, and quality of life were evaluated preoperatively and postoperatively.The study enrolled 106 eyes (53 patients; age range 49 to 80 years). All groups had significant improvement in uncorrected and corrected distance visual acuities postoperatively (P ≤.05). Near vision outcomes were significantly better in Groups B and C (P ≤.01). Groups B and C had significantly less difficulty in some near tasks, such as reading the newspaper (A-B, P=.02; A-C, P=.02) or reading bills (A-B, P=.04; A-C, P=.004). Group C also had significantly less difficulty driving at night than Group B (P.01). Near visual acuity and contrast sensitivity were significantly correlated with difficulty in near visual tasks in Groups B and C. Night-driving difficulty correlated significantly with contrast sensitivity in Group B.Patients with multifocal IOLs could perform several daily tasks at near and intermediate distances, with less night-driving limitation with the full diffractive IOL than with apodized multifocal and monofocal IOLs.No author has a financial or proprietary interest in any material or method mentioned.

To use anterior segment optical coherence tomography (AS-OCT) to evaluate the stability of a recently released angle-supported phakic intraocular lens (pIOL) in the anterior segment with changes in pupil diameter.Keratoconus Unit, Vissum Corporation, Alicante, Spain.In this observational cross-sectional study of consecutive eyes with moderate to high myopia, an AcrySof Cachet pIOL was implanted with the aim of minimizing the refractive error. An analysis of the position and stability of the pIOL before and after pharmacologic pupil dilation was performed 3 months postoperatively using the Visante AS-OCT system. A measurement protocol that included several anatomic parameters was developed and applied; the parameter values before and after dilation were compared.Twenty eyes of 20 patients ranging in age from 24 to 48 years old were evaluated. The anterior chamber depth increased significantly with pupil dilation (mean change 0.06 mm +/- 0.08 [SD]) (P.01). A significant change was also observed in the distance between the center of the cornea at the endothelial plane and the anterior surface of the pIOL (mean change 0.03 +/- 0.05 mm) (P = .01). The distances between the peripheral edges of the pIOL and the corneal endothelium and the distance between the crystalline lens and the pIOL did not change significantly (Por=.14).The angle-supported pIOL showed excellent intraocular behavior after pupil dilation, with no shortening of the distance between the pIOL and corneal endothelium at the center or peripheral edges of the pIOL.

In addition to being a protective shield, the cornea represents two thirds of the eye's refractive power. Corneal pathology can affect one or all of the corneal layers, producing corneal opacity. Although full corneal thickness keratoplasty has been the standard procedure, the ideal strategy would be to replace only the damaged layer. Current difficulties in corneal transplantation, mainly immune rejection and shortage of organ supply, place more emphasis on the development of artificial corneas. Bioengineered corneas range from prosthetic devices that solely address the replacement of the corneal function, to tissue-engineered hydrogels that allow regeneration of the tissue. Recently, major advances in the biology of corneal stem cells have been achieved. However, the therapeutic use of these stem cell types has the disadvantage of needing an intact stem cell compartment, which is usually damaged. In addition, long ex vivo culture is needed to generate enough cell numbers for transplantation. In the near future, combination of advanced biomaterials with cells from abundant outer sources will allow advances in the field. For the former, magnetically aligned collagen is one of the most promising ones. For the latter, different cell types will be optimal: 1) for epithelial replacement: oral mucosal epithelium, ear epidermis, or bone marrow- mesenchymal stem cells, 2) for stromal regeneration: adipose-derived stem cells and 3) for endothelial replacement, the possibility of in vitro directed differentiation of adipose-derived stem cells towards endothelial cells provides an exciting new approach.

Purpose To evaluate the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization. Design Prospective, nonrandomized, interventional case series. Methods setting: Institutional, multicenter clinical trial. study population: Twenty eyes from 20 patients with stable corneal neovascularization. intervention procedures: Patients were treated with topical 1.0% bevacizumab for 3 weeks and were monitored for a total of 24 weeks. main outcome measures: Primary outcome measures included: neovascular area, defined as the area of the corneal vessels themselves; vessel caliber, defined as the mean corneal vessel diameter; and invasion area, defined as the fraction of the total cornea into which the vessels extended. The occurrence of ocular and systemic adverse events was monitored closely. Results As compared with the baseline visit, patients exhibited a statistically significant improvement in neovascular area by week 6 ( P = .007) and in vessel caliber by week 12 ( P = .006). At the final visit, neovascular area, vessel caliber, and invasion area were reduced by 47.5%, 36.2%, and 20%, respectively. The decreases in neovascular area and vessel caliber were statistically significant ( P P = .003, respectively); however, the reduction in invasion area did not reach statistical significance ( P = .06). There were no significant changes in the secondary outcomes, and there were no adverse events. Conclusions Short-term topical bevacizumab treatment reduced the extent of stable corneal neovascularization as measured by neovascular area and vessel caliber with no associated adverse events. Interestingly, the degree of treatment efficacy was inversely proportional to the baseline invasion area.