Ugur Acar

Efficacy of Topical Mesenchymal Stem Cell Therapy in the Treatment of Experimental Dry Eye Syndrome Model

Purpose. The current study was set out to address the therapeutic efficacy of topically applied mesenchymal stem cells (MSCs) on dry eye syndrome (DES) induced by benzalkonium chloride (BAC) in rats. Methods. Rats were divided into two groups just after establishment of DES. Eye drops containing either bromodeoxyuridine labeled MSCs (n = 9) or phosphate buffer solution (n = 7) were topically applied once daily for one week. Schirmer test, break-up time score, ocular surface evaluation tests, and corneal inflammatory index scoring tests were applied to all rats at baseline and after treatment. All rats were sacrificed after one week for histological and electron microscopic analysis. Results. Mean aqueous tear volume and tear film stability were significantly increased in rats treated with MSCs (P < 0.05). Infiltration of bromodeoxyuridine labeled MSCs into the meibomian glands and conjunctival epithelium was observed in MSCs treated rats. Increased number of secretory granules and number of goblet cells were observed in MSCs treated rats. Conclusion. Topical application of MSCs could be a safe and effective method for the treatment of DES and could potentially be used for further clinical research studies.

Reducing the Histopathological Changes of Radioiodine to the Lacrimal Glands by a Popular Anti-Oxidant: Lycopene

Abstract Purpose of the study: Radioiodine (RAI) has been used for the treatment of hyperthyroidism and well-differentiated thyroid carcinoma for more than 70 years. Lycopene is an anti-oxidant, which is plentiful in red fruits. The purpose of this study was to investigate the possible inhibitory effect of lycopene on the RAI-induced acute histopathological changes in rat lacrimal glands. Methods: In this experimental animal study, 32 rats were randomly divided into three groups. The first group (control group, n = 8) was not given neither 131I nor lycopene, the second group (RAI group, n = 12) was administrated a single dose of 3 mCi 131I and 1 cc physiologic saline by gastric gavage. The third group (lycopene group, n = 12) was administrated 3 mCi 131I and 1 cc lycopene by gastric gavage. After 24 h of the last dose, the animals were decapitated on the seventh day and their lacrimal glands were removed for histopathological examination. Results: The cell shape and the cell size variation and poorly defined acidophilic cell outlines in all lacrimal glands were observed significantly less frequently in the lycopene group than in the RAI group. Conclusions: Our histopathological examinations have revealed that lycopene prevents rat lacrimal glands against RAI-related acute histopathological changes.

Effect of allogeneic limbal mesenchymal stem cell therapy in corneal healing: role of administration route.

Aims: To investigate whether allogeneic limbal mesenchymal stem cell (LMSC) therapy affects corneal healing after a severe chemical burn and whether the route of administration of LMSCs differs in its therapeutic effect in this respect. Methods: A total of 60 Sprague-Dawley rats with clinically proven alkali injury were divided into four equal groups (n = 15) as follows: group 1: 2 × 105 cells/drop LMSCs, topically applied 6 times a day for 2 days; group 2: 2.4 × 106 cells in 0.5 ml LMSCs, subconjunctivally applied; group 3: 2.4 × 106 cells in 1 ml LMSCs, intraperitoneally applied, and group 4: no LMSC treatment. The groups were compared according to grades of corneal opacity (CO), corneal neovascularization (CNV) and corneal fluorescein staining (CFS). The migration of LMSCs into the cornea and the inflammatory characteristics of the groups were evaluated with BrdU (5-bromo-2′-deoxyuridine bromodeoxyuridine) immunostaining and histopathologically in a 4-week follow-up. Results: There were statistically significant differences between the LMSC-treated and control groups in each week regarding mean CO scores and in the 3rd week regarding the mean CNV and CFS scores (p < 0.05). The statistical significance was due to the differences between the topical and the control group and between the subconjunctival and the control group. BrdU+ LMSCs were seen in the corneal epithelium of the all LMSC-administered rats, and fewer inflammatory changes were observed in these rats. Conclusion: Allogeneic LMSC treatment, especially topical and subconjunctival administration, seems to be helpful in affecting corneal healing after a severe corneal burn.

Posttraumatic Intraocular Pressure Elevation and Associated Factors in Patients with Zone I Open Globe Injuries

1Department of Ophthalmology, Kastamonu State Hospital, Kastamonu; 2Department of Ophthalmology, Ankara Training and Research Hospital, Ankara, Turkey. #Current affiliation: Department of Ophthalmology, Hacettepe University, Kastamonu Faculty of Medicine, Ankara, Turkey. 1Kastamonu Devlet Hastanesi, Goz Klinigi, Kastamonu; 2Ankara Egitim ve Arastirma Hastanesi, Goz Klinigi, Ankara. #Şimdiki kurumu: Hacettepe Universitesi Kastamonu Tip Fakultesi Goz Hastaliklari Anabilim Dali, Ankara.BACKGROUND The object of this study was to determine factors that might be associated with intraocular pressure (IOP) elevation after anterior segment open globe injuries (zone I). METHODS Data were obtained from the records of 68 patients who experienced zone I open globe injury between January 2008 and October 2010. Group I was composed of patients with chronically elevated IOP of at least 21 mmHg within a 1-year follow-up period. The rate of posttraumatic IOP elevation and associated structural and functional risk factors were evaluated. RESULTS Of the 68 patients, 17 (25%) developed posttraumatic IOP elevation (Group 1). The mean age in group I was significantly older compared to group II (36.8±24.4 and 15.7±15.3 years, respectively [p=0.003]). Iris damage, postoperative inflammation, and use of long-term corticosteroids were significantly greater in group I (p<0.001, p<0.001, p=0.005 respectively). In group I, 13 of 17 patients (76.5%) had a wound size larger than 6 mm compared to only one patient (1/51, 2%) in group II, and the result was statistically significant (p<0.001). The size of wound larger than 6 mm also retained its statistical significance in multivariate analysis (p<0.001, odds ratio: 162.5). CONCLUSION This study shows a significant relationship between larger wound size (>6 mm) and elevation of IOP after trauma in zone I open globe injuries.

Analysis of the horizontal corneal diameter, central corneal thickness, and axial length in premature infants

PURPOSE To determine the horizontal corneal diameter, central corneal thickness, and axial length in premature infants. METHODS Infants with a birth weight of less than 2,500 g or with a gestation period of less than 36 weeks were included in the study. Infants with retinopathy of prematurity (ROP) were allocated to Group 1 (n=138), while those without ROP were allocated to Group 2 (n=236). All infants underwent a complete ophthalmologic examination, including corneal diameter measurements, pachymetry, biometry, and fundoscopy. Between-group comparisons of horizontal corneal diameter, central corneal thickness, and axial lengths were performed. Independent sample t-tests were used for statistical analysis. RESULTS Data was obtained from 374 eyes of 187 infants (102 female, 85 male). The mean gestational age at birth was 30.7 ± 2.7 weeks (range 25-36 weeks), the mean birth weight was 1,514 ± 533.3 g (range 750-1,970 g), and the mean postmenstrual age at examination was 40.0 ± 4.8 weeks. The mean gestational age and the mean birth weight of Group 1 were statistically lower than Group 2 (p<0.05). There were no significant differences in horizontal corneal diameter, central corneal thickness, and axial length between the two groups (p>0.05). CONCLUSIONS The presence of ROP in premature infants does not alter the horizontal corneal diameter, central corneal thickness, or axial length.

The effects of commonly used intravitreal steroids on proliferation index of ciliary body-derived mesenchymal stem cells: an in vitro study

Abstract Aim: To investigate the effects of commonly used intravitreal steroids on survival and proliferation (namely, proliferation index) of ciliary body-derived mesenchymal stem cells (CB-MSC). Methods: CB-MSCs were isolated from newborn rats’ eye, and they were expanded in the medium. Commonly used intravitreal steroids such as dexamethasone (Dex) and triamcinolone acetonide (TA) were added into the medium at commonly used concentration in clinical practice (0.1 mg/mL) and at lower concentration (0.01 mg/mL). Proliferation indexes of CB-MSCs were analyzed with the xCELLigence system at nine consecutive times (at 3rd, 6th, 21th, 30th, 45th, 60th, 75th, 90th and 100th h). Results: Both TA and Dex at both 0.01 mg/mL and 0.1 mg/mL concentrations had negative effect on proliferation indexes of CB-MSC. Although negative effect of TA on proliferation index of CB-MSC at both concentrations was not statistically significant, statistically significant negative effect of Dex at 0.01 mg/mL concentration started 60th h (p = 0.017) and 0.1 mg/mL concentration started 30th h (p = 0.014). Discussion: Even therapeutic doses of intravitreal corticosteroid agents might have negative effects on limited numbers of stem cells. Especially, Dex caused statistically significant toxic effects on CB-MSCs even at lower concentrations of those used clinically. These novel findings deserve further in vivo investigations.

The relationship of birth weight, gestational age, and postmenstrual age with ocular biometry parameters in premature infants

PURPOSE To analyze ocular biometry parameters and evaluate their relationship with gestational age, birth weight, and postmenstrual age in prematurely born infants. METHODS The right eyes of 361 premature infants born before the 36th gestational week were evaluated. Birth weight, gestational week, and gender were recorded. An A-scan Biometer was used for obtaining axial measurements, including anterior chamber depth, lens thickness, vitreous length, and total axial length. RESULTS Gestational age and birth weight values ranged from 23 to 36 weeks and from 560 to 2,670 g, respectively. The mean gestational age and birth weight were 30.8 ± 2.8 weeks and 1,497.9 ± 483.6 g, respectively. During the first examination (4-5 weeks of postnatal age), birth weight and gestational age of the infants correlated significantly and positively with lens thickness, vitreous length, and axial length (r>0.5, p<0.001), but not with anterior chamber depth (r<0.5). Increased vitreous and axial lengths correlated significantly with increasing postmenstrual age of the infants (r=0.669, p<0.001; r=0.845, p<0.001, respectively). CONCLUSIONS Lens thickness, vitreous length, and axial length, but not anterior chamber depth, were significantly correlated with birth weight and gestational age. All four parameters increased with increasing postmenstrual age, with higher correlations for vitreous and axial lengths than for anterior chamber depth and lens thickness. It was concluded that axial elongation resulted primarily from increasing posterior chamber length.

Microphthalmia in a Case of Edward Syndrome

Abstract Aim: To present an infant of trisomy 18 (Edwards Syndrome) with unilateral microphthalmia. Methods: A female infant who was born at 41 weeks of gestation had been diagnosed with Edwards Syndrome (ES). On ophthalmic examination, microphthalmia, microcornea, optic disc coloboma, and persistent hyaloid artery were determined in the left eye. In addition, abnormalities in the ears, hands, feet, and cardiovascular system were present. Discussion: With this case report, we aimed to highlight the relationship between ocular disgenesis and chromosomal disorders and the importance of prenatal testing and genetic counseling for parents.

Prostaglandin E2 Levels of Aqueous and Vitreous Humor in Ketorolac 0.4% and Nepafenac 0.1% Administered Healthy Rabbits.

ABSTRACT Purpose: To compare the lowering effects of ketorolac 0.4% and nepafenac 0.1% on aqueous and vitreous humor prostaglandin E2 (PGE2) levels in rabbits. Methods: Ketorolac and nepafenac ophthalmic solutions were administered to the right eyes of 24 healthy rabbits after randomized division into two groups. The left eyes of these rabbits were considered as controls for the two groups. On the 4th day of the experiment, the samples were taken from the aqueous and vitreous humors of the rabbits bilaterally, and PGE2 levels were measured by an enzyme immune assay kit. Results: Ketorolac and nepafenac achieved a statistically significant decrease (p<0.001, for each) in PGE2 levels in the aqueous (11.75 ± 6.15 and 14.75 ± 7.60 pg/mL, respectively) and the vitreous humor (6.58 ± 4.62 and 9.83 ± 4.55 pg/mL, respectively). Conclusions: Both ketorolac and nepafenac inhibited PGE2 levels in both the aqueous and vitreous humors of rabbits. Although PGE2-lowering effects were similar in the aqueous humor, nepafenac seemed to be more potent than ketorolac in the vitreous humor.

The effects of smoking on dry eye parameters in healthy women

Abstract Aim: To investigate the effects of chronic smoking on dry eye parameters. Methods: Ocular surface disease index (OSDI) and tear function tests such as Schirmer’s test, tear break-up-time (TBUT) test and impression cytology of 63 female chronic smokers and 40 age-matched female non-smokers were analyzed statistically. Results: The mean OSDI scores, Schirmer test results and TBUT levels were 35.85 ± 24.01 point, 14.25 ± 5.94 mm and 5.17 ± 2.85 s in chronic smokers and 15.20 ± 12.93 point, 15.48 ± 7.01 mm and 10.03 ± 3.44 s in non-smokers, respectively. Differences in OSDI scores, TBUT levels and impression cytology grades among the chronic smokers and non-smokers were statistically significant. Conclusion: Smoking behavior seems to affect the dry eye parameters negatively.