Hasan Basri Çakmak

Preparation and Characterization of Triamcinolone Acetonide-loaded Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHx) Microspheres

Triamcinolone acetonide loaded in poly(3-hydroxybutyrate-co-3 hydroxyhexanoate) (PHBHx) microspheres were prepared to treat cystoid macular oedema (CMO) and acute posterior segment inflammation associated with uveitis. The PHBHx microspheres were prepared by solvent evaporation technique using methylene chloride as the solvent and aqueous poly(vinyl alcohol) emulsifier as the dispersion medium. The PHBHx microspheres obtained were well formed with narrow size distribution; the average size prepared ranged from 40—200 μm depending on the formulation used. The stirring rate of the dispersion medium, emulsifier concentration, and polymer/solvent ratio parameters were varied to determine their effect on the size and size distribution of the PHBHx microspheres. Increasing the stirring rate and emulsifier concentration decreased the size and the size distribution of the microspheres, while increasing the polymer/solvent ratio caused the opposite effect. The polymer/drug ratio was the most effective parameter for controlling drug loading and release properties. More than 90% of the loaded drug was released within the first 24 h; after that, the release rate was slower for all formulations.

Preparation and In Vitro/In Vivo Evaluation of Cyclosporin A-Loaded Nanodecorated Ocular Implants for Subconjunctival Application

In terms of ocular drug delivery, biodegradable implant systems have several advantages including the ability to provide constant drug concentration at the target site, no necessity for surgical removal, and minimum systemic side effects. Cyclosporin A (CsA) is a neutral, hydrophobic, cyclic peptide of amino acids that frequently used for dry eye disease treatment. The aim of this study was to develop a nanoparticle-loaded implant system for sustained-release CsA delivery following subconjunctival implantation. Poly(lactide-co-glycolide) (85:15) or poly-ε-caprolactone (PCL) were used to prepare two different nanoparticle formulations. These nanoparticles loaded into PCL or poly(lactide-co-caprolactone) implant formulations were prepared by two different methods, which were molding and electrospinning. Size and zeta potential of nanoparticles were determined and the morphology of the formulations were investigated by scanning electron microscopy. CsA-loading efficiencies were calculated and the in vitro degradation and in vitro release studies were performed. MTT test was also performed using L929 fibroblast cells to evaluate the cytotoxicity of the formulations. PCL-PCL-NP-I formulation was implanted to Swiss Albino mice with induced dry eye syndrome to evaluate the efficacy. In vitro release studies showed that the release from the formulations continues between 30 and 60 days, and the cell viability was found to be 77.4%-99.0%. In vivo studies showed that healing is significantly faster in the presence of the selected implant formulation. Results indicated that nanodecorated implants are promising ocular carriers for controlled-release CsA application.

Short-term effects of intravitreal bevacizumab (Avastin(®)) on retrobulbar hemodynamics in patients with neovascular age-related macular degeneration.

Acta Ophthalmol. 2011: 89: e41–e45

Time course of silicone oil emulsification.

Purpose: To investigate the natural course of silicone oil emulsification after silicone oil tamponade usage in retinal detachment surgery. The presence of a group of patients whose silicone oil tamponades we preferred to keep as long as possible because of high risk of redetachment enabled us to investigate the course of in vivo silicone oil emulsification. Methods: Thirty-two cases that were considered to have a high risk of redetachment after silicone oil removal were closely monitored, and it was preferred to keep the silicon oil as long as possible until first signs of silicone oil emulsification were observed. Any ocular complication directly related to the silicone oil tamponade did not arise in any of these cases, and the only indication for silicone oil removal was the signs of emulsification. Results: The silicone oil emulsification time ranges from 5 months to 24 months with a mean of 13.2 ± 4.8 months. In most cases, it occurs within the first year. However, there are also 2 cases where emulsification is not observed until the 24th month. Conclusion: It could be possible to extend the silicone oil removal time up to 1 year to achieve a stable retinal status in cases with a high risk of redetachment.

Refractive Error May Influence Mesopic Pupil Size

Purpose: To identify factors which affect mesopic pupil diameter in refractive surgery patients. Setting: This retrospective study was performed at the 1st Ophthalmology Clinic in Ankara Ataturk Training and Research Hospital, Ankara, Turkey. Methods: Medical records of 412 refractive surgery candidates who applied between 2006 and 2008 were reviewed. Detailed ophthalmological examination data were obtained from medical records. Pupil size measurements were performed with a COAS Ocular Wavefront analyzer in mesopic conditions. Relationship between mesopic pupil diameter and age, sex, spherical refractive error (D), magnitude of astigmatism (D), type of astigmatism, spherical equivalent, and average keratometry were analyzed by means of univariate and multivariate regression analyses. Results: Mean mesopic pupil diameter was 6.19 ± 0.88 mm. Mean pupil diameter (mean ± standard deviation) was 5.70 ± 1.01 in hypermetropia, 6.04 ± 0.79 mm in mixed astigmatism, and 6.33 ± 0.82 mm in myopia. The difference in mean mesopic pupil diameters between myopes and hypermetropes was statistically significant (p = 0.001). However, differences with regard to mean pupil diameters between myopes and mixed astigmatism (p = 0.660) and between hypermetropes and mixed astigmatism (p = 0.109) were not significant. Mean pupil diameter was 6.00 ± 0.99 mm in against the rule astigmatism, 5.96 ± 0.84 mm in oblique astigmatism, and 6.27 ± 0.84 mm in with the rule astigmatism. Mean mesopic pupil diameter in with the rule astigmatism group was higher than oblique astigmatism group. Spherical refractive error (r = -0.213, p = 0.001), cylindrical refractive error (0.197, p = 0.001), and age (r = −0.341, p = 0.001) showed correlation with pupil diameter. Conclusions: This study showed that age and magnitude of both spherical and cylindrical refractive error are the most determinative factors on mesopic pupil size.

Effects of intracameral use of adrenalin solution with preservative on corneal endothelium

Objective: To evaluate the effects of injection of 1:100,000 dilution adrenalin with sodium bisulfite preservative on the corneal endothelium in phacoemulsification cataract surgery. Methods: This retrospective study comprised 70 patients with age-related cataracts who had undergone phacoemulsification cataract surgery with intraocular lens (IOL) implantation without any surgical complications. In the adrenalin group, patients with intraoperative intracameral adrenalin use were included. The intracameral adrenalin was composed of 1 mL of 1:100,000 dilution adrenalin with sodium bisulfite preservative. The control group included patients who underwent surgery without any intracameral adrenaline use. There were 36 patients in the adrenalin group and 34 patients in the control group. Corneal endothelial density, endothelial cell morphology, and endothelial cell area were measured via specular microscopy both preoperatively and 3 months after surgery. The 2 groups were compared with regard to changes in specular microscopy measurements. Results: The mean (± standard deviation) age was 66.51 ± 8.32 years in the adrenalin group and 67.58 ± 7.83 years in the control group. The difference in age between the 2 groups was not significant (p = .611). The preoperative mean corneal endothelial cell density was 2,270 ± 286 cells/mm2 in the adrenalin group and 2,226 ± 260 cells/mm2 in the control group, and the difference between the 2 groups was not statistically significant (p = .550). In the adrenalin group, the postoperative mean corneal endothelial cell density was 2,191 ± 268 cells/mm2. Although the postoperative mean cell density was lower than the preoperative mean cell density, the difference between the 2 measurements was not statistically significant (p = .117). In the control group, the postoperative mean corneal endothelial cell density was 2,169 ± 272 cells/mm2, and the difference between the preoperative and postoperative measurements was not statistically significant (p = .161). Comparisons of postoperative specular microscopy measurements between the adrenalin and control groups with regard to cell density, cell sizes, and cell shapes showed that there were no statistically significant differences in comparison of all parameters between the 2 groups. Conclusions: Intracameral injection of 1:100,000 dilution adrenalin with sodium bisulfite preservative is not toxic to corneal endothelium.

In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano-decorated subconjunctival implants

Abstract Biodegradable implants are promising drug delivery systems for sustained release ocular drug delivery with the benefits such as minimum systemic side effects, constant drug concentration at the target site and getting cleared without surgical removal. Dry eye syndrome (DES) is a common disease characterized with the changes in ocular epithelia surface and results in inflammatory reaction that might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is frequently employed for the treatment of DES and it needs to be applied several times a day in tear drops form. The aim of this study was to evaluate in vivo behavior and efficacy of the developed nano-decorated subconjunctival implant systems for sustained release CsA delivery. Biodegradable Poly-ɛ-caprolactone (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co-glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve sustained release. Two of the formulations PCL–PLGA–NP-F and PCL-PCL-NP-I were selected for in vivo evaluation based on their in vitro characteristics determined in our previous study. In this study, formulations were implanted to Swiss Albino mice with induced dry eye syndrome to investigate the ocular distribution of CsA following subconjunctival implantation and to evaluate the efficacy. Tissue distribution study indicated that CsA was present in ocular tissues such as cornea, sclera and lens even 90 days after the application and blood CsA levels were found lower than ocular tissues. Efficacy studies also showed that application of CsA-loaded fiber implant formulation resulted in faster recovery based on their staining scores.

Suspected Bacterial Endophthalmitis Following Sustained-release Dexamethasone Intravitreal Implant: A Case Report

A 58-year-old man admitted to our opthalmology department with the complaint of branch retinal vein occlusion. He was treated with intravitreal Ozurdex in the right eye. Two days after the injection, the patient presented with ocular pain and the visual acuity was hand movement. A diagnosis of endophthalmitis was made. We performed emergent pars plana vitrectomy (PPV) and the implant was removed from the vitreous cavity using a retinal forceps. A combination of vancomycin 1.0 mg and amikacin 0.4 mg was injected intravitreally. However, because of the blurring in the vitreus one week after the procedure, phacoemulsification and a repeat PPV was performed. Five days after the last procedure the signs and symptoms of endophthalmitis were resolved. Our case demonstrated that endophthalmitis could develop after intravitreal implantation of Ozurdex. Surgical removal of the implant and immediate vitrectomy seems to be a useful treatment option in these cases.

Effects of topical dorzolamide on IOP after phacoemulsification with different types of ophthalmic viscosurgical devices.

Purpose To evaluate the effect of topical dorzolamide on postoperative intraocular pressure (IOP) after routine phacoemulsification surgery with different type of ophthalmic viscosurgical device (OVD). Methods Patients who were scheduled for phacoemulsification with intraocular lens (IOL) implantation were evenly divided into four groups. Group I (83 eyes) received one drop of topical dorzolamide immediately after surgery and 1.4% NaHa (BD Visc®) was used as a cohesive OVD during IOL implantation. Group II (83 eyes) did not receive any topical antiglaucoma medication after operation and 1.4% NaHa was used as a cohesive OVD. Group III (83 eyes) received topical dorzolamide and 1% NaHa (Healon®) was used, and Group IV (83 eyes) did not receive any topical and 1% NaHa was used in operation. Mean postoperative IOPs were compared between groups. Results Eyes with 1.4% NaHa usage (18.2±9.2 mmHg) had higher mean postoperative IOPs than eyes with 1% NaHa usage (15.5±5.3 mmHg) (p=0.002). Mean postoperative IOPs were lower in eyes with dorzolamide application (15.6±7.2 mmHg) than in eyes without any medication (18.1±8.5 mmHg) both in eyes with 1.4% NaHa and 1% NaHa usage (p=0.003). Dorzolamide application caused an average 2.5 mmHg decrease in mean postoperative IOPs in both groups. Conclusions Effects of OVDs on IOP rises after phacoemulsification surgery are closely related to their molecular structure. Increase in viscosity rendered higher postoperative IOP increments. However, topical dorzolamide application effectively reduced postoperative IOP increments in eyes with both Healon® and BD Visc® use. (Eur J Ophthalmol 2007; 17: 38–44)

Corneal white-to-white distance and mesopic pupil diameter.

AIM To study the relationship between corneal white-to-white (WTW) distance and mesopic pupil diameter. METHODS This study is composed of 30 cases that underwent photorefractive keratotomy (PRK). Pupil size measurements were performed with Schwind ORK wavefront analyzer in mesopic conditions. WTW distance was measured with a measuring caliper. Also, A-scan ultrasound examination was performed in all patients. The relationship among the mesopic pupil diameter and age, sex, axial length, lens thickness, anterior chamber depth(ACD), horizontal WTW distance, vertical WTW distance, spherical equivalent, and average keratometry were analyzed with univariate and multivariate regression analysis. RESULTS Mean pupil diameter was (6.39±0.80)mm (range: 3.70mm-7.73mm). Horizontal WTW distance measurements were between 11.00mm and 12.50mm and mean horizontal WTW distance was (11.79±0.43)mm. On the other hand, vertical WTW distances ranged between 10.00mm and 13.00mm, and their mean was (11.42±0.72)mm. Bivariate correlation between pupil diameter and other variables showed that the axial length, ACD, spherical equivalent, and horizontal WTW distance had a moderate correlation with mesopic pupil diameter. Multiple regression analysis revealed that spherical equivalent and horizontal WTW distances were significantly associated with mesopic pupil diameter (R=0.598, R(2)=0.358 P=0.02). CONCLUSION This study shows that mesopic pupil diameter is closely related to horizontal WTW distance. These two factors must be taken in consideration together in preoperative ablation zone planning.