Tuomo Puustjärvi

Matrix metalloproteinases and their inhibitors in the chamber angle of normal eyes and patients with primary open-angle glaucoma and exfoliation glaucoma

BackgroundIn glaucoma, extensive pathological changes occur in the trabecular meshwork (TM) and juxtacanalicular tissue of the chamber angle. Aqueous humor drainage is disturbed due to the accumulation of extracellular matrix (ECM) material in the outflow system. Matrix metalloproteinases (MMPs) remodel ECM material and, thus, they may have a role in regulating outflow facility and intraocular pressure (IOP). This study examined the expression of MMPs and tissue inhibitors of MMPs (TIMPs) in the chamber angle of normal eyes and in primary open-angle glaucoma (POAG) and in exfoliation glaucoma (ExG).MethodsTM tissues were isolated from healthy donor eyes for corneal transplantation. Specimens of the inner wall of Schlemm’s canal and the juxtacanalicular tissue were collected from patients with POAG or ExG during deep sclerectomy operation. Monoclonal antibodies against MMPs (MMP-1, -2, -3, and -9) and antibodies against TIMPs (TIMP-1, -2, and -3) were used for immunohistochemical stainingResultsImmunoreactivity for MMP-2, TIMP-2, or TIMP-3 was observed in human normal TM and in the inner wall of Schlemm’s canal. In general, immunoreactions for all of the tested MMPs were more intense in POAG samples than in ExG samples or in the control group. The only exception was the MMP-2 level, which was the highest in the control group. The staining intensity of MMP-1 or MMP-3 was significantly higher in POAG when compared to ExG. TIMP-1 was significantly increased in POAG compared with ExG and there were no marked differences in the levels of TIMP-2 or TIMP-3 between POAG and ExG. The ratios of MMP-1/TIMP-1 and MMP1+2+3+9 and TIMP1+2+3 were significantly higher in samples from POAG compared to those of ExG.ConclusionsOur results reveal an expression imbalance between MMPs and their endogenous tissue inhibitors in tissue samples from patients with POAG and ExG. Differences in immunohistochemical reactions reflect discrete local pathogenic mechanisms involved in POAG and ExG. With respect to the proposed role of MMPs in the remodeling of ECM material, this may point to a weaker reactivity to the accumulation of ECM material in TM in ExG than POAG eyes.

Myopic shift and its mechanism in nephropathia epidemica or Puumala virus infection.

Nephropathia epidemica (NE) is a zoonose caused by Puumala virus. NE belongs to the group of haemorrhagic fevers with renal syndrome. Transient myopia has been described in the acute phase of the disease. This prospective study presents the changes of refraction and the results of ophthalmic A scan measurements of patients who were managed at Savonlinna Central Hospital for NE during an epidemic in the winter of 1992-3. This involved 37 patients and 74 eyes. The incidence of transient myopia was 8.1% and that of myopic shift 40.5%. A scan ultrasound measurements were performed in patients in the acute phase and after total recovery of their general illness. Statistical analysis revealed that there were significant differences in anterior chamber depth and lens thickness between the acute and control phases of the disease and between the patients who had myopic shift compared with those who did not have a significant myopic change in refraction. Based on these results it seems that the reason for transient myopic shift of NE is mainly a combination of two factors: forward movement of the anterior diaphragm and thickening of the crystalline lens. The term myopic shift should be used rather than transient myopia because it better describes the overall refractive change in NE.

Mitomycin C‐augmented deep sclerectomy in primary open‐angle glaucoma and exfoliation glaucoma: a three‐year prospective study

Purpose:  To investigate the efficacy and safety of mitomycin C (MMC)‐augmented deep sclerectomy with implant (DSCI) in primary open‐angle glaucoma (POAG) and exfoliation glaucoma (ExG) patients.

PRACTICAL PROBLEMS IN THE USE OF OCUSERT®-PILOCARPINE DELIVERY SYSTEM

The effects of the long‐acting pilocarpine preparation, Ocusert®, were studied by its application for one week into a total of 52 eyes of 42 earlier untreated glaucoma patients. From the diurnal pressure curves it was found to be equivalent to three daily administrations of 2 or 4% pilocarpine topically, the experiences were as follow: 8 of the preparations had to be removed before the end of the experiment due to insufficient effect and two were removed for other reasons; 19 fell out accidentally, 3 were displaced so as to be visible occasionally under the eyelid, but did not fall out; 2 patients succeeded in replacing the preparation after it had fallen out. In the 19 eyes (37%) of all patients still in the trial after the first day, the preparations stayed in place without any difficulty for the whole week. All patients experienced minor side‐effects, but only one of them terminated the treatment due to these side‐effects. Serious side‐effects did not occur.

The Effects of 5-Fluorouracil on Ocular Tissues In Vitro and In Vivo after Controlled Release from a Multifunctional Implant

PURPOSE To evaluate the effects of 5-fluorouracil (5-FU) on ocular cells in vitro and the effects of degradable 5-FU-loaded poly(DL-lactide-co-glycolide; PDLGA) 50:50 implant in the rabbit eye in vivo. METHODS Cytotoxicity was assessed with a tetrazolium salt WST-1 cell proliferation/viability test and a lactate dehydrogenase (LDH) leakage test in rabbit corneal stromal fibroblasts (SIRCs), bovine corneal endothelial cells (BCECs), human conjunctival epithelial cells (IOBA-NHCs), human retinal pigment epithelial cells (ARPE-19), and human corneal epithelial cells (HCECs). The 5-FU-loaded PDLGA implants were surgically placed in rabbit eyes with a deep sclerectomy technique and the histopathology of the eyes was examined. RESULTS In vitro, 5-FU affected cell proliferation and survival in a time- and dose-dependent manner. In the WST-1 test, adverse effects in serum-free conditions started from 0.0005 mg/mL 5-FU in SIRCS and HCECs, whereas in other cell types, 0.005 mg/mL 5-FU hindered cell proliferation. In serum-free conditions 72-hour 5 mg/mL 5-FU treatment decreased cell viability to 40% in BCECs and to 10% to 15% in other cell types. 5-FU had no or very minor effects on LDH leakage. In vivo, the 5-FU implant showed no signs of toxicity in cornea and retina, whereas in the conjunctival stroma near the implantation site, some inflammatory cells and a marked subepithelial condensation of stromal connective tissue was observed during the postoperative period of 4 weeks. CONCLUSIONS 5-FU had a broad therapeutic range, and the 5-FU implant showed only minor tissue reactions in conjunctiva at the surgical site. 5-FU is a possible candidate for controlled drug release.

Differences in retinal neovascular tissue and vitreous humour in patients with type 1 and type 2 diabetes

Aims: The aim of the study was to evaluate the histopathology of neovascular tufts and vitreous samples collected from patients with diabetes. Methods: Vitreous samples and neovascular tufts were collected from patients with type 1 (n = 13) and (n = 17) type 2 diabetes with proliferative retinopathy, and from controls with a macular hole (n = 5). Neovessels were analysed using immunohistochemistry and vitreous samples with an enzyme-linked immunosorbent assay (ELISA). The main outcome measure was to examine differences in the levels of growth factors in patients with type 1 and type 2 diabetes with proliferative retinopathy. Results: Vascular endothelial growth factor (VEGF)-A was most strongly present in the samples from patients with type 1 diabetes. In type 2 diabetes, VEGF-D was more abundantly present than in type 1 diabetes. Angiopoietin (ANG)-2 was also abundantly present. Macrophages and nuclear factor kappa B (NFκB) were found, indicating the presence of an inflammatory process in the neovascular tissues. Conclusions: VEGF-A and ANG-2 are equally important in the neovascular process in both type 1 and type 2 diabetes. VEGF-D is abundantly present in type 2 diabetes. In order to achieve better control of diabetic retinopathy, it might be beneficial to develop treatments that prevent the actions of ANG-2 and VEGF-D.

Retinal fixation of traumatic retinal detachment with metallic tacks: a case report with 10 years' follow-up.

Background Retinal rupture and detachment caused by traumatic ocular perforation has a poor prognosis without extensive repair procedures. The authors describe the phases of treatment of a complex injury in a 21-year-old man with a traumatic retinal rupture in whom metallic tacks were used for retinal fixation. The report does not include histopathology. Methods Observational case report and literature review. The outcome of a 10-year follow-up is evaluated at the latest visit by determining the visual acuity (VA) and by observing the state of retina and tacks. Results A traumatic retinal rupture with detachment was treated with titanium tacks for retinal fixation. By inserting a total of 13 metallic tacks for the repair of a temporal postequatorial retinal rupture and adjacent retinal detachment a successful outcome was achieved. Two additional operations were performed to reattach the retina of nasal hemisphere in the same eye. One dislodged tack was removed at the final operation. Ten years later, at the last intervention, VA was 12/20 in the injured eye. The retina was completely attached, and the remaining 12 tacks were in place, although six of them were partially pushed up by an encircling band. Proliferative vitreoretinopathy (PVR) was absent, and a relatively narrow circumferential zone of scar tissue adjacent to the row of tacks was visible. The patient occasionally experienced glare in the affected eye, but was otherwise symptom-free. Conclusion Reports of long-term experiences with mechanical retinal refixation with metallic tacks are scarce. Especially in extended use, the tacks are claimed to cause several complications, including PVR. Although modern ophthalmic surgery offers a variety of methods for retinal reattachment, the complexity of the damage caused by trauma may lead to a dead end in refixation attempts. Nevertheless, retinal tacks may represent an adjunctive remedy in complex retinal detachment cases.

Conjunctival matrix metalloproteinases and their inhibitors in glaucoma patients

Chronic conjunctival inflammation, caused by various reasons, for example long‐term use of topical drugs and/or their preservatives, affects the outcome of glaucoma surgery by interfering with wound healing. Matrix metalloproteinases (MMPs) remodel extracellular matrix (ECM) and are involved in the wound healing process. This study was designed to evaluate the conjunctival expression of MMPs and their tissue inhibitors (TIMPs) in the normal eye, primary open‐angle glaucoma (POAG) and exfoliation glaucoma (ExG) and whether there is an association between staining intensities and deep sclerectomy outcome.

Mitomycin‐C‐augmented deep sclerectomy in patients with primary open‐angle glaucoma and exfoliation glaucoma: a 1‐year prospective study

Purpose:  To investigate the efficacy and safety of mitomycin C (MMC)‐augmented deep sclerectomy with implant (DSCI) in patients with primary open‐angle glaucoma (POAG) and exfoliation glaucoma (ExG).

Phospholipases A2 in normal human conjunctiva and from patients with primary open-angle glaucoma and exfoliation glaucoma

BackgroundChronic situations like long-term use of topical medications induces conjunctival inflammation and is also a significant risk factor for failure of filtering surgery. We evaluated conjuctival expression of group IIA secretory PLA2 (sPLA2-IIA), group V secretory PLA2 (sPLA2-V), calcium-independent PLA2 (iPLA2) and cytosolic PLA2 (cPLA2).MethodsSamples were obtained from non-glaucomatous patients (control subjects), and patients with either primary open-angle glaucoma (POAG) or exfoliation glaucoma (ExG). All the glaucoma patients had been treated with antiglaucomatous medication, and underwent deep sclerectomy surgery. Antibodies against sPLA2-IIA, sPLA2-V, iPLA2 and cPLA2 were used for immunohistochemical staining of frozen tissue sections.ResultsIn the human conjunctiva of non-glaucomatous patients, immunostaining of sPLA2-IIA, sPLA2-V or cPLA2 was low and positively stained cells were mainly localized in the surface of the epithelium. In contrast, iPLA2 was found to predominate in human normal conjunctiva and it demonstrated strong labeling throughout the epithelium. The stromal staining of iPLA2 was weak. Expression of sPLA2-IIA was significantly increased in stromal fibers of patients with POAG or ExG. No changes were found in levels of sPLA2-V, iPLA2 or cPLA2 between the patient groups and controls.ConclusionsThese findings demonstrate that sPLA2-IIA, sPLA2-V, iPLA2 and cPLA2 are expressed in the conjunctiva of non-glaucomatous patients. In the epithelium, sPLA2-IIA, sPLA2-V, and cPLA2 may participate in protection against risks caused by mechanical wear and tear stress whereas iPLA2 may regulate remodeling and maintenance of membrane phospholipids. sPLA2-IIA may also have the important role in the degradation of bacteria. In conjunctival stroma of POAG and ExG patients, sPLA2-IIA may play a role in the development of scar tissue after glaucoma filtration surgery.