A multi-organ chip with matured tissue niches linked by vascular flow.

Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions. Each tissue is cultured in its own optimized environment and is separated from the common vascular flow by a selectively permeable endothelial barrier. The interlinked tissues maintained their molecular, structural and functional phenotypes over 4 weeks of culture, recapitulated the pharmacokinetic and pharmacodynamic profiles of doxorubicin in humans, allowed for the identification of early miRNA biomarkers of cardiotoxicity, and increased the predictive values of clinically observed miRNA responses relative to tissues cultured in isolation and to fluidically interlinked tissues in the absence of endothelial barriers. Vascularly linked and phenotypically stable matured human tissues may facilitate the clinical applicability of tissue chips.

Comparing the effects and safety of dorzolamide hydrochloride + timolol maleate versus brimonidine after neodymium-doped yttrium aluminium garnet laser capsulotomy posterior capsule opacification.

AIM: Posterior capsular opacification is treated using neodymium-doped yttrium aluminium garnet laser capsulotomy that leads to increased intraocular pressure. Here, we compare the effects of dorzolamide hydrochloride + timolol maleate versus brimonidine on intraocular pressure. We also investigate their side effects after neodymium-doped yttrium aluminium garnet laser capsulotomy. In these patients, there are no prior studies comparing the results of these two drugs. MATERIALS: Ninety patients with posterior capsule opacification contributed to the study. They received yttrium aluminium garnet laser capsulotomy. After yttrium aluminium garnet laser capsulotomy, they were randomized into three groups. Group 1 received dorzolamide hydrochloride + timolol maleate; Group 2 took brimonidine; and Group 3, the control group, took no drug. Group 1 took dorzolamide hydrochloride + timolol maleate eye drops 1 h before the procedure and on the third hour of the first day and two times per day between the second and the seventh days. Group 2 took brimonidine eye drops 1 h before the procedure and on the third hour of the first day, two times per day between the second and the seventh days. RESULTS: Brimonidine had a similar side effect profile to the fix combination. Intraocular pressure on the first (p = 0.87) and third days (p = 0.124) were similar in Group 1 (dorzolamide hydrochloride + timolol maleate), Group 2 (brimonidine) and the control group. The mean intraocular pressure value of the control group was significantly higher than Groups 1 and 2 because the anti-glaucomatous effects of the drugs become prominent on the seventh day (p = 0.041). In Group 1 and Group 2, intraocular pressure was significantly lower than the control group on the seventh day (p = 0.041). Stinging, itching, hyperemia and Tyndall rates were similar in Group 1, Group 2 and the control group. Watery eyes were less common in the brimonidine group than in the dorzolamide hydrochloride-timolol maleate and the control groups on the seventh day (p = 0.02). Brimonidine also significantly lowered the chemosis rate on the third (p = 0.04) and seventh (p = 0.03) days. CONCLUSION: We suggest that brimonidine and a combination of dorzolamide + timolol are similarly effective at reducing eye pressure for routine cases. In cases where intraocular pressure attacks might be at higher risk, using the dorzolamide + timolol combination would be more appropriate.

Chloroquine and hydroxychloroquine retinopathy-related risk factors in a Turkish cohort.

To evaluate the role of previously reported risk factors on developing retinopathy in patients treated with chloroquine (CQ) and hydroxychloroquine (HCQ). Ophthalmologic examination, visual field testing, and spectral domain-optical coherence tomography were performed in 31 patients treated with CQ and HCQ. Toxicity diagnosis was proven by electrophysiological assessment. The risk factors reported by the American Academy of the Ophthalmology (AAO) were compared between patients with (n = 5) and without toxicity (n = 26) findings. Risk score was calculated for each patient. CQ daily overdose per actual body weight was significantly higher in affected patients. There was no statistically significant difference between groups concerning risk score, estimated cumulative dose of CQ, daily dose of HCQ and CQ per lean body weight, daily overdose of CQ per lean body weight and actual body weight (>3 mg/kg). The cumulative dose of HCQ was significantly higher in non-affected patients. The risk factors reported by the AAO might not be applicable to all CQ- and HCQ-treated patients. Different risk factors not yet reported may play a role in the development of CQ and HCQ retinopathy.

HIV-related eye disease in patients presenting to a tertiary care government hospital in Turkey.

AIM: To document the ocular involvement in HIV-infected individuals in Turkey and to compare the findings with those from other centers throughout the world. METHODS: In this cross-sectional study, patients with HIV infection being monitored in a tertiary hospital in Istanbul were enrolled. Ocular examination was performed, and the prevalence of ocular manifestations determined. RESULTS: In total, 93 patients were enrolled, of whom 37.6% had ocular pathology. HIV retinopathy was the most frequent retinal finding, affecting 8.6% of the enrolled patients, but none of the affected individuals had any ophthalmic complaints. There were no ocular lesions suggestive of cytomegalovirus (CMV) retinitis. DISCUSSION: In contrast to the case in the developed world, sight-threatening infections are uncommon in Turkish HIV(+) patients. The reasons for this are not clear, but it is possible that there are some genetic or environmental protective factors against CMV retinitis in the population studied.

The relationship between optical coherence tomography patterns, angiographic parameters and visual acuity in age-related macular degeneration.

To assess the relationships between visual acuity (VA), fluorescein angiographic parameters and optical coherence tomography (OCT) patterns in exudative age-related macular degeneration (AMD). Fifty eyes with confirmed diagnosis of new exudative AMD who underwent fluorescein angiography (FA) and OCT evaluation were reviewed retrospectively. The greatest linear diameter of lesion (GLD) by FA and central foveal thickness (CFT) by OCT were measured. The OCT scans were evaluated for the presence of diffuse retinal thickening (D), cystic spaces (C), subretinal fluid (S) and pigment epithelial detachment (P) and five OCT patterns were detected (D + S; C; C + S; P + C + S; P + D + S). Angiographic classification of choroidal neovascularizations was performed. Correlations were statistically significant for VA and CFT in all patients whereas VA and GLD correlation was statistically significant only in predominantly classic and minimal classic lesions. The lowest VA values were detected in patients with COCT pattern and/or predominantly classic lesion type by FA. The OCT and FA findings when evaluated simultaneously may provide information regarding visual function in AMD.

Screening for retinopathy of prematurity in a tertiary hospital in Istanbul: incidence and risk factors.

PURPOSE: To study the incidence and risk factors of retinopathy of prematurity (ROP) in premature infants examined in a tertiary hospital in Istanbul. METHODS: Data of infants screened for ROP from April 2007 to September 2009 were retrospectively reviewed. Possible risk factors and eye examinations were recorded and analyzed using the chi-square test and univariate and multivariate regressions. RESULTS: ROP was detected in 177 (34.3%) of the 517 infants enrolled in the study; 64 had mild ROP (77.4%) and 38 had severe ROP (22.6%). The mean gestational age and birth weight of patients who were treated for ROP were 28.6 ± 2.3 and 1,143.5 ± 337.4, respectively. Two of these infants had a gestational age of 32 g or greater and three had a birth weight of 1,500 g or greater. The multivariate regression analyses showed gestational age, birth weight, sepsis, respiratory distress syndrome, and length of oxygen therapy as independent predictors of ROP. CONCLUSION: The incidence of ROP observed in this study was higher than that in developed countries and relatively more mature infants were affected. Criteria including gestational age of less than 34 weeks or birth weight of less than 2,000 g would have identified all infants who were at risk.

Deep sclerectomy augmented with combination of absorbable biosynthetic sodium hyaluronate scleral implant and mitomycin C or with mitomycin C versus trabeculectomy: long-term results.

BACKGROUND: To evaluate the long-term results following deep sclerectomy with mitomycin C-SKgel implant (DSMMC-SKgel), mitomycin C (DSMMC) and trabeculectomy. DESIGN: Comparative case series, Goztepe Training and Educational Hospital. PARTICIPANTS: Ninety-one open-angle glaucoma patients. METHODS: DSMMC-SKgel, DSMMC and trabeculectomy operations were performed in 28, 30 and 33 eyes, respectively. MAIN OUTCOME MEASURES: Intraocular pressures (IOP) and distance corrected visual acuities (DCVA) were measured preoperatively and postoperatively at days 1, 7 and months 1, 3, 6, 12, 18, 24, 30, 36, 48. RESULTS: At month 48, deep sclerectomy groups had better DCVAs, and in all groups mean IOPs and number of medications were significantly lower and DCVAs were worse than preoperative values. Mean IOPs in trabeculectomy group at week 1, months 1 and 3 were significantly lower than those in DSMMC group. Mean IOPs in DSMMC-SKgel group at week 1 and month 1 were significantly lower than those in DSMMC group. Mean preoperative IOPs, postoperative IOPs following 3rd month, complete (IOP ≤ 21 mmHg and ≤ 18 mmHg without medication) and qualified (IOP ≤ 21 mmHg and ≤ 18 mmHg with or without medication) success rates of all groups were not statistically different. Rate of complications such as hyphema, hypotony, shallow anterior chamber, bleb leak, bleb fibrosis, cataract, choroidal detachment and macular oedema were found to be significantly higher in trabeculectomy group (P < 0.05). No significant difference in the mean post-laser goniopuncture IOPs was found between the two deep sclerectomy groups during the follow up. CONCLUSIONS: DSMMC, DSMMC-SKgel and trabeculectomy operations were almost equally effective in lowering IOP at long-term follow up, but complication rates were higher after trabeculectomy operations.

A cluster of acute-onset postoperative endophthalmitis over a 1-month period: investigation of an outbreak caused by uncommon species.

AIM: To report the clinical course, treatment response and prognosis of eight cases which developed acute-onset postoperative endophthalmitis over a 1-month period. METHODS: 8 patients who were operated on over a period of 1 month and developed acute postoperative endophthalmitis were evaluated. Five of the patients had cataract surgery, one had cataract surgery combined with silicone extraction, and two patients had pars plana vitrectomy (PPV). Clinical patterns were observed, intraocular cultures were obtained, and the source of the organisms causing the epidemic was investigated. All patients had intravitreal antibiotic injections, three had PPV, and in two patients anterior chamber irrigation was performed. RESULTS: Vitreous cultures showed Cellulosimicrobium cellulans in three cases and Stenotrophomonas maltophilia in one case. Four of the cases were culture negative. Stenotrophomonas maltophilia were also isolated from unused bottles of irrigating solutions. The final visual acuity of the patients ranged between HM and 7/10. All three patients with Cellulosimicrobium cellulans had a final visual acuity of ≥ 5/10. The available irrigating solutions were changed, and the endophthalmitis did not recur. CONCLUSIONS: The authors are unaware of any previous reports of postoperative endophthalmitis associated with Cellulosimicrobium cellulans. Prompt management with microbiological support, intravitreal antibiotics and PPV when needed were the key to good visual outcomes in this endophthalmitis outbreak.

Idiopathic Hypertrophic Cranial Pachymeningitis Associated With Intermediate Uveitis.

The authors report a case with idiopathic hypertrophic cranial pachymeningitis associated with intermediate uveitis. The patient complained of decreased vision in both eyes, especially the right. Ophthalmic examination revealed right optic disc pallor, bilateral vitritis, and cystoid macular edema. Magnetic resonance imaging revealed marked enhancement of a dural lesion. The macular edema responded well to medical treatment. Intermediate uveitis has not yet been reported in the context of idiopathic hypertrophic cranial pachymeningitis.

Twenty-four-hour intraocular pressure control with latanoprost-timolol-fixed combination versus bimatoprost in patients who switched from timolol.

PURPOSE: To evaluate bimatoprost versus latanoprost and timolol fixed combination (LTFC) over the 24-hour diurnal curve in patients who switched from timolol. METHODS: In this prospective, observer-masked, randomized clinical trial, 64 patients whose intraocular pressures (IOPs) were not effectively controlled with timolol were enrolled. At pretrial visit IOPs and central corneal thickness were measured. After the baseline visit, timolol was replaced by bimatoprost or LTFC. IOPs were recorded at 8 AM, noon, 4 PM, 8 PM, midnight, and 4 AM at baseline, week 8, and week 16 visits. RESULTS: At baseline and week 8 visits, there was no significant difference between the LTFC and bimatoprost group for the mean IOPs at 6 time points in 24 hours, the mean diurnal IOP, and range of diurnal IOP. At week 16, the mean IOP of the bimatoprost group (15.7±2 mm Hg) at 8 AM and 12 o' clock, midnight, was statistically significantly lower than that of the LTFC group (16.8±1.5 and 16.9±1.7 mm Hg; P=0.03 and 0.002). A statistically significant difference was not found between the proportions of patients who had 15% and 20% decrease in mean diurnal IOP and the mean daytime, nighttime, diurnal IOP reductions of the 2 study groups at weeks 8 and 16 (P>0.05). In the bimatoprost group punctate epitheliopathy, conjunctival hyperemia, and lid erythema were found to be more frequent. CONCLUSIONS: The LTFC and bimatoprost therapies were equally effective in maintaining IOP at lower levels during the 24-hour period in patients who switched from timolol therapy. Adverse events were more frequent with bimatoprost therapy.

Visual performances with monofocal, accommodating, and multifocal intraocular lenses in patients with unilateral cataract.

PURPOSE: To compare the visual performance of patients with unilateral cataract following implantation of monofocal, accommodating, refractive, and diffractive multifocal intraocular lenses (IOL). DESIGN: Prospective nonrandomized clinical trial. METHODS: Eighty-seven patients with unilateral cataract were enrolled in 4 groups for phacoemulsification and IOL implantation. Twenty-four patients had monofocal (Alcon Acrysof) (group 1), 21 patients had accommodating (Human Optics 1CU) (group 2), 22 patients had diffractive multifocal (Tecnis ZM900) (group 3), and 20 patients had refractive multifocal (AMO Rezoom) (group 4) IOL implantations. Ages of patients were between 40 and 70. Parameters analyzed at the 18th postoperative month were subjective refractions, monocular and binocular distance, intermediate and near uncorrected visual acuities, monocular distance and near best-corrected visual acuities, monocular distance-corrected intermediate and near visual acuities, stereopsis, visual complaints, and spectacle dependency. RESULTS: No significant difference was observed between distance and near best-corrected visual acuities of IOL groups, and between intermediate visual acuities of groups 2, 3, and 4. Groups 3 and 4 had statistically better near vision than the other groups (P < .05). No significant difference was observed between near visual acuities of groups 3 and 4. Number of patients with better stereoscopic function, spectacle independence, and complaints of halo in groups 3 and 4 was significantly higher than in other groups (P < .05). CONCLUSIONS: Multifocal IOLs provide better stereopsis, higher spectacle independence rates, and satisfactory functional vision over a broad range of distances in presbyopic patients with unilateral cataract compared with the monofocal and accommodating IOLs.

Differences in contrast sensitivity between monofocal, multifocal and accommodating intraocular lenses: long-term results.

BACKGROUND: To evaluate long-term contrast sensitivity (CS) and visual acuity following implantation of monofocal, accommodating, refractive and diffractive multifocal intraocular lenses (IOLs) in patients with unilateral cataract. METHODS: In this prospective non-randomized clinical trial, 87 patients with unilateral cataract were enrolled in four groups for phacoemulsification and IOL implantation in Ophthalmology Department of Goztepe Training and Research Hospital. Twenty-four patients had monofocal (Alcon Acrysof; group 1), 21 patients accommodating (Human Optics 1CU; group 2), 22 patients diffractive multifocal (Tecnis ZM900; group 3) and 20 patients refractive multifocal (AMO Rezoom; group 4) IOL implantations. Ages of patients were between 40 and 70. Parameters analysed at the 18th postoperative month were subjective refractions, monocular and binocular distance and near photopic CSs, visual acuities. RESULTS: Near visual acuities were statistically better in group 3 than the other groups (P < 0.05). At low spatial frequencies, mean monocular distance CSs of group 1 and mean monocular near CSs of groups 1 and 2 were statistically higher than those of group 4 (P < 0.05). There was no significant difference between binocular CSs of group 4 and the other groups at low spatial frequencies. At high spatial frequencies, monocular and binocular CSs of groups 1 and 2 were statistically higher than those of groups 3 and 4 (P < 0.05). Near CSs was better in group 3 than group 4. CONCLUSIONS: In patients with unilateral cataract, monofocal, accommodating and partially diffractive multifocal IOL provided higher CS scores when compared with refractive multifocal IOL and in multifocal IOL groups binocular CSs were better than monocular CSs when compared with other groups.

Detecting retinal vigabatrin toxicity in patients with partial symptomatic or cryptogenic epilepsy.

PURPOSE: Detecting retinal vigabatrin toxicity in patients with partial symptomatic or cryptogenic epilepsy can be challenging because of preexisting visual field defects secondary to a structural abnormality in the brain or lack of collaboration. The aim of this study was to measure the retinal nerve fiber layer thickness (RNFLT) with optic coherence tomography (OCT), as well as contrast sensitivity, color vision, and perimetry, in patients with partial symptomatic or cryptogenic epilepsy on vigabatrin, and to determine the efficacy of these tests as markers of vigabatrin-related retinal damage in these subgroups of epileptic patients. METHODS: The study involved 38 patients with either partial symptomatic or cryptogenic epilepsy and 16 healthy individuals comprising the control group. At the time of the study, 14 of the patients were using vigabatrin, 10 were receiving sodium valproate monotherapy, and 14 were on carbamazepine monotherapy. All the participants underwent RNFLT imaging with OCT, contrast sensitivity, color discrimination assessment, and perimetry. RESULTS: The average 360 degrees RNFLT of the vigabatrin group was significantly lower when compared to the other groups. The average RNFLT of all quadrants except the temporal one in the vigabatrin group was also significantly reduced. There was no difference in the mean deviation, contrast sensitivity, and color discrimination between the study groups, but they were all significantly lower than the control group. CONCLUSIONS: RNFLT measurement with OCT can efficiently identify vigabatrin toxicity in patients with partial symptomatic and cryptogenic epilepsy. Perimetry, contrast sensitivity, and color discrimination assessment might be inconclusive in these particular subgroups of epileptic patients.

Visual acuity and contrast sensitivity function after accommodative and multifocal intraocular lens implantation.

PURPOSE: To evaluate visual acuities and contrast sensitivities (CS) after accommodative, refractive, and diffractive multifocal intraocular lens (IOL) implantations. METHODS: After cataract extractions, in 20 eyes accommodative IOL (group 1), in 30 eyes refractive IOL (group 2), and in 20 eyes diffractive multifocal IOL (group 3) implantations were performed. CS were measured with the stereo optical functional acuity contrast test. Uncorrected distance (UCDVA) and distance corrected near visual acuities (DCNVA) and refractive values were determined. RESULTS: The mean UCDVA (0.99+/-0.03) and DCNVA (0.98+/-0.04) of group 3 were significantly better than the other IOL groups. The mean DCNVA of group 2 (0.71+/-0.14) was significantly better than group 1 (0.5+/-0.08). One month after the operations CS, values of group 2 were significantly lower than the 2 other IOL groups. Photopic CS values of group 1 at 12 and 18 cycles per degree (cpd) were significantly higher than group 3. Three months after the operations, CS values of group 1 and 3 were significantly higher than that of group 2 at 3, 6, 12, and 18 cpd and in all spatial frequencies respectively. There was no difference between groups 1 and 3 with respect to photopic CS values. Mesopic CS values of group 3 were significantly higher than that of group 1 at 1.5, 3, and 6 cpd. At the 6th and 12th month, CS values of group 3 were similar or better compared to the values of the 3rd month. CONCLUSIONS: The diffractive multifocal IOL resulted in more favorable visual acuities and higher CS values than accommodative and refractive multifocal IOL.

Optical coherence tomography findings in pseudoxanthoma elasticum.

PURPOSE: To describe optical coherence tomography (OCT) findings of ocular lesions in pseudoxanthoma elasticum (PXE). METHODS: Sixteen eyes of 8 patients with PXE and 20 eyes of 10 age-matched healthy volunteers were included in the study. All patients in the study and control group underwent a complete ophthalmologic examination and OCT. Fluorescein angiography was performed on the patients with PXE. RESULTS: In the areas of peau de orange mottling, OCT demonstrated increased reflectivity on the level of retinal pigment epithelium (RPE), Bruch membrane, and choriocapillaris complex. OCT scans of crystalline body showed a hyperreflective shell and an isoreflective or hyporeflective core. OCT scans of the angioid streaks demonstrated thinning in RPE-Bruch membrane-choriocapillaris complex. CONCLUSIONS: Disturbances on the level of RPE, choroid, and Bruch membrane may be responsible for the ocular lesions in PXE. OCT may give clues to the pathophysiology of the retinal lesions. Spectral domain OCT could provide more details and information. Further studies using this new technology should be performed.

The prevalence of anisometropia aniso-astigmatism and amblyopia in neurofibromatosis type 1.

PURPOSE: The purpose of this study was to document the prevalence of anisometropia, anisoastigmatism, and anisometropic amblyopia in patients with neurofibromatosis-1 (NF1) and to compare it with that in age- and sex-matched controls. METHODS: Fifty patients with NF1 and 150 age- and sex-matched controls were examined in this study. Cycloplegic autorefraction was attempted on all patients <16 years old and without cycloplegia on patients >16 years old. Anisometropia was defined as absolute interocular difference of spherical equivalent more than or equal to 1 D. Aniso-astigmatism was defined as interocular difference of refractive astigmatism of more than or equal to 1 D. Amblyopia was defined as two-line decrease in Snellen acuity between the two eyes. RESULTS: The overall prevalence of anisometropia, aniso-astigmatism, and amblyopia in patients with NF1 was 16%, 20%, and 10%, respectively, and they were all significantly higher than in the controls. The amblyopia was either moderate or severe in nature and all affected patients had significant astigmatism (>2.5 D) in the amblyopic eye. CONCLUSIONS: NF1 is a risk factor for anisometropia, aniso-astigmatism, and aniso-astigmatic amblyopia and screening patients with NF1 for refractive errors before age 3 will help to detect patients at risk of amblyopia and give them proper treatment.

Rimexolone 1% versus prednisolone acetate in preventing early postoperative inflammation after cataract surgery.

PURPOSE: To compare the efficacy and safety of rimexolone 1% and prednisolone acetate 1% ophthalmic suspensions in controlling intraocular inflammation in the early period after cataract surgery. METHODS: Eighty patients undergoing cataract extraction with intraocular lens implantation, either planned extra capsular cataract extraction (PECCE) or phacoemulsification surgery, were evaluated in a prospective, randomized, observer-masked, clinical trial in which efficacy in controlling early postoperative inflammation and safety of prednisolone acetate 1% one eye drop every 4 h (n = 36 eyes) was compared with that of rimexolone 1% one eye drop every 4 h (n = 44 eyes) in an eighteen day course. Efficacy was assessed from changes of the anterior chamber cell count, flare, conjunctival hyperemia, and ciliary congestion by means of slit lamp biomicroscopy on days 1, 3, 8, 15, and 18. Intraocular pressure (IOP) and possible side effects were also recorded on each visit. RESULTS: Anterior chamber cell count and flare showed no difference in the two groups at any visits. The rimexolone group was associated with significantly higher score for conjunctival hyperemia on days one and three (P < 0.05) and the prednisolone acetate group was associated with a significantly higher score for corneal edema on day 8 (P < 0,05). However, there were no between group differences in IOP. CONCLUSIONS: Rimexolone 1% ophthalmic suspension was as effective and safe as prednisolone acetate 1% ophthalmic suspension in controlling inflammation in the early period after cataract surgery.