Maki Nishikawa

Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy

PURPOSE To determine the levels of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in the vitreous of patients with diabetic retinopathy (DR). DESIGN Experimental study of PEDF and VEGF levels in vitreous samples collected during vitrectomy. METHODS The levels of PEDF and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 46 eyes of 43 patients who underwent vitrectomy with diabetic retinopathy (DR) (32 eyes of 29 patients) and an idiopathic macular hole (MH) (14 eyes of 14 patients). RESULTS The vitreal concentration of PEDF was significantly lower at 1.11 +/- 0.14 microg/ml (mean +/- standard error) in eyes with DR than in eyes with MH at 1.71 +/- 0.22 microg/ml (P =.021). The VEGF level was 1799 +/- 478 pg/ml in eyes with DR and not detectable in MH. The PEDF level in proliferative DR (PDR) (0.94 +/- 0.12 microg/ml) was lower than that in nonproliferative DR (NPDR) (2.25 +/- 0.32 microg/ml), and that in active DR (0.85 +/- 0.14 microg/ml) was significantly lower than that in inactive DR (1.59 +/- 0.24 microg/ml; P =.01). The VEGF level was 2025 +/- 533 pg/ml in PDR and 215 +/- 201 pg/ml in NPDR and that in active DR (2543 +/- 673 pg/ml) was significantly higher than that in inactive DR (395 +/- 188 pg/ml; P =.0098). CONCLUSIONS These results suggest that lower levels of PEDF and higher levels of VEGF may be related to the angiogenesis in DR that leads to active PDR.

Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy and high in rhegmatogenous retinal detachment

PURPOSE To report the levels of pigment epithelium-derived factor in the vitreous of patients with diabetic retinopathy, rhegmatogenous retinal detachment, and idiopathic macular hole. METHODS Using enzyme-linked immunosorbent assay, we measured the levels of pigment epithelium-derived factor in the vitreous of 34 eyes of 33 patients who underwent vitrectomy for the treatment of diabetic retinopathy (17 eyes of 16 patients), rhegmatogenous retinal detachment (10 eyes), and idiopathic macular hole (seven eyes). RESULTS The vitreal concentration of pigment epithelium-derived factor was 1.15 +/- 0.23 microg/ml (mean +/- standard error) in eyes with diabetic retinopathy, 3.28 +/- 0.69 microg/ml in rhegmatogenous retinal detachment, and 1.71 +/- 0.39 microg/ml in idiopathic macular hole. The pigment epithelium-derived factor level in rhegmatogenous retinal detachment was significantly higher than that in diabetic retinopathy (P =.0008) and idiopathic macular hole (P =.034). For eyes with diabetic retinopathy, the pigment epithelium-derived factor level was 0.88 +/- 0.21 microg/ml in proliferative diabetic retinopathy and 2.43 +/- 0.37 microg/ml in nonproliferative diabetic retinopathy (P =.0083). Additionally, the pigment epithelium-derived factor level in active diabetic retinopathy (0.70 +/- 0.22 microg/ml) was significantly lower than the level in inactive diabetic retinopathy (1.79 +/- 0.35 microg/ml; P =.018). CONCLUSIONS These results suggest that pigment epithelium-derived factor inhibits angiogenesis and that lower levels of pigment epithelium-derived factor may be related to the angiogenesis in diabetic retinopathy and result in active proliferative diabetic retinopathy. The results also suggest that higher levels of pigment epithelium-derived factor in the eyes with rhegmatogenous retinal detachment may act as a neuroprotective agent for the detached retina.

Inverse levels of pigment epithelium-derived factor and vascular endothelial growth factor in the vitreous of eyes with rhegmatogenous retinal detachment and proliferative vitreoretinopathy

PURPOSE To determine the vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in eyes with rhegmatogenous retinal detachment and proliferative vitreoretinopathy. DESIGN Prospective, noncomparative case series. METHODS Pigment epithelium-derived factor and vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay in 26 eyes with retinal detachment, 6 with proliferative vitreoretinopathy, and 14 with an idiopathic macular hole. RESULTS Pigment epithelium-derived factor concentration in proliferative vitreoretinopathy (0.57 +/- 0.05 microg/ml) was lower (P =.0069), and retinal detachment (2.37 +/- 0.34 microg/ml) was higher (P =.16) than that in macular hole (1.71 +/- 0.22 microg/ml). Vascular endothelial growth factor concentration (168 +/- 139 microg/ml) in proliferative vitreoretinopathy was significantly higher than that in retinal detachment (11 +/- 11 microg/ml, P =.0084) and macular hole (not detectable, P =.0095). CONCLUSION Lower levels of pigment epithelium-derived factor and higher levels of vascular endothelial growth factor may be related to ocular cell proliferation.

Comparison of surgical outcomes of combined viscocanalostomy and cataract surgery with combined trabeculotomy and cataract surgery

PURPOSE To compare the outcomes of combined viscocanalostomy, phacoemulsification, and intraocular lens (IOL) implantation with combined trabeculotomy, phacoemulsification, and IOL implantation in patients with primary open-angle glaucoma (POAG). DESIGN Nonrandomized clinical trial. METHODS Fifty-seven eyes (57 POAG patients) that underwent viscocanalostomy, phacoemulsification, and intraocular lens (IOL) implantation between March 2000 and April 2001 and were followed for over 6 months postoperatively comprised the viscocanalostomy (VCS) group. Fifty-seven of 105 eyes (105 POAG patients) that underwent trabeculotomy, phacoemulsification, and IOL implantation between April 1995 and February 2000 and were followed for over 6 months and < 2 years comprised the trabeculotomy (LOT) group. The reductions of postoperative intraocular pressure (IOP) and antiglaucoma medication use in both groups were compared. Best-corrected visual acuity (VA) and complication rates were secondary outcomes. The success probabilities related to postoperative IOP level in both groups were evaluated by Kaplan-Meier life-table analysis with log-rank test. RESULTS Significant reductions of IOP and antiglaucoma medication use occurred in both groups up to 1 year postoperatively, but were not significantly different between the two groups. The success probabilities of the VCS group for IOP control under 21, 17, and 15 mm Hg were 95%, 74%, and 44%, respectively, at 6 months, 95%, 67%, and 32% at 1 year, and not significantly different from the LOT group. All eyes in the VCS group had VA equal to or better than baseline 3 months postoperatively. The incidences of postoperative fibrin reaction (14 eyes, 25%) and microperforations of the Descemet membrane (14 eyes, 25%) in the VCS group were higher than in the LOT group (P =.0004 and P <.0001, respectively). CONCLUSIONS Intraocular pressure reduction and VA improvement after the two procedures were similar in Japanese patients with POAG and cataract.

A comparison of optic disc topographic parameters in patients with primary open angle glaucoma, normal tension glaucoma, and ocular hypertension

BackgroundHeidelberg Retina Tomograph (HRT) findings have been employed to quantitatively assess the topography of optic discs. We measured topographic parameters of optic discs in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and ocular hypertension (OH) using an HRT in order to determine whether HRT topographic parameters can be used to differentiate those conditions.MethodsSeventeen eyes in 17 patients with POAG, 23 eyes in 23 patients with NTG, and 15 eyes in 15 patients with OH were examined using an HRT, and the results were analyzed by age, refractive error, and topographic parameters.ResultsAmong the HRT parameters, the mean values for rim area, rim volume, cup disk area ratio, and classification showed significant differences among POAG, NTG, and OH eyes. The mean values for cup area, cup volume, mean RNFL thickness, and RNFL cross section area showed significant differences between POAG and NTG eyes, and NTG and OH eyes, however, not between POAG and OH eyes. Cup shape measure showed significant differences between POAG and OH, and NTG and OH eyes, but not between POAG and NTG eyes.ConclusionsOur results suggest that POAG is distinguishable from NTG and OH based on evaluations of rim area and rim volume. Patients with NTG tend to have larger cupping, smaller rims, and thinner retinal nerve fiber layers as compared to POAG and OH patients. Thus, HRT topographic parameters are useful to differentiate patients with POAG, NTG, and OH.

Ultrasound biomicroscopy of intrascleral lake after viscocanalostomy and cataract surgery.

To assess anatomic changes at the sclerectomy site after combined viscocanalostomy and cataract surgery associated with POAG or OH and cataract. Methods:In a prospective, noncomparative, longitudinal study, we performed ultrasound biomicroscopy (UBM) of the sclerectomy site in 84 eyes at 3, 6, and 12 months after the surgery. Four parameters in UBM findings (area, radial longitudinal length, height of intrascleral space, and meridional length of window) were measured and the IOP level, the number of antiglaucoma medications, and bleb formation were observed for 12 months. Results:Intraocular pressure decreased from 19.8 ± 3.5 (± SD) mm Hg preoperatively to 15.5 ± 3.0 mm Hg 12 months postoperatively (P < 0.0001). Blebs were formed in 2 of 84 eyes (2.4%) at 1 month, and 1 of 84 eyes (1.2%) after 3 months. The IOP decreased at 3, 6, and 12 months postoperatively by 5.8, 4.8, and 4.3 mm Hg, respectively (P = 0.0016). A significant difference was observed between 3 months and 12 months in area (0.17 and 0.13 mm2, respectively, P = 0.0127 using the Bonferroni/Dunn test), longitudinal length (0.89 and 0.72 mm, P = 0.0059), and height (0.21 and 0.15 mm, P < 0.0001), but not in meridional length (0.41 and 0.33 mm). The lake was present in 66.7% of cases at 12 months. Conclusion:Combined viscocanalostomy and cataract surgery lowered IOP without bleb formation. Postoperatively, the size of the lake and IOP decreased, suggesting parallel reduction of the two. The lake was undetected ultrasonographically in one third of the cases 1 year postoperatively.

Combined viscocanalostomy and cataract surgery compared with cataract surgery in Japanese patients with glaucoma.

PurposeTo compare intraocular pressure (IOP) and the incidence of complications after combined viscocanalostomy and cataract surgery with cataract surgery alone in 206 Japanese eyes with POAG or OH. Patients and MethodsIn a nonrandomized comparative, clinical study, 103 eyes underwent viscocanalostomy and cataract surgery (VCS group), and 103 eyes underwent cataract surgery alone (CSA group) (follow-up, 6–24 months). Reductions in IOP and medications, the probability of successful IOP reduction visual acuity changes, and complications were compared between the 2 groups. ResultsThe reductions in IOP and number of medications in the VCS group were significantly greater than in the CSA group (P ≤ 0.0038 and P ≤ 0.0259, respectively). The probabilities of achieving IOPs less than 21, 18, and 15 mm Hg at 24 months in the VCS groups were 85.0%, 53.6%, and 17.2% with medications, and 61.1%, 43.9%, and 16.2% without medications, and significantly better than in the CSA group (P < 0.0002). The visual outcomes were similar in both groups. Postoperative complications such as hyphema and fibrin formation, although more frequent in the VCS group, were not vision threatening. ConclusionCombined viscocanalostomy and cataract surgery provides good postoperative visual acuity with minimal complications and significantly greater IOP reduction than cataract surgery alone for Japanese patients with glaucoma.

Senescence in cultured trabecular meshwork cells

Background: It has been suggested that replicative senescence might be involved in the pathophysiology of age-related diseases. Aim: To study the process of senescence in trabecular meshwork (TM) cells. Methods: Porcine TM tissues were obtained and placed in primary cultures with Dulbecco’s modified Eagle’s medium/Ham’s F-12 medium. After 2–3 weeks, migrated and proliferated TM cells were trypsinised and cultured in serial passages, and identified with fluorescein-labelled low-density lipoprotein (DiI-Ac-LDL), a marker of TM cells. Staining for senescence-related β-galactosidase activity was performed at population doubling level (PDL) 2, 8 and 16 at pH 6. Terminal restriction fragment (TRF) length was examined by Southern blot analysis using a 32P-labelled telomere-specific sequence (TTAGGG)3 at each PDL. Results: DiI-Ac-LDL staining revealed that most (nearly 100%) of the cells in the culture were TM cells, which were flattened in shape and positive for senescence-related β-galactosidase staining at PDL 16. Reduction of TRF length as a function of population doubling was also shown. Conclusions: TM cells exhibited characteristics of senescence at PDL 16 in vitro. The results demonstrated that cellular senescence may be related to the pathophysiology of primary open-angle glaucoma.

Indocyanine Green Angiography in Experimental Choroidal Circulatory Disturbance

Purpose: To determine how choroidal venous congestion alters the indocyanine green angiograms (ICGA) of monkeys. Methods: Two vortex veins in each eye of 5 Japanese macaque monkeys were sutured and cauterized at their exit. ICGA and fluorescein angiography (FA) were performed immediately after the occlusions. The FA and ICGA findings were correlated with the histopathological changes. Results: ICGA showed a delay in filling the choroidal arteries in the field of the occluded vortex veins, and the choroidal veins were filled retrogradely in a pulsatile manner. The fluorescence intensity of the larger veins was higher in the occluded area. The clearance of the indocyanine green dye was delayed by approximately 15 min. Histology showed that the choroidal veins in the occluded field were engorged with red blood cells. Conclusion: The ICGA findings in eyes with choroidal venous congestion are a delay in the filling of the choroidal arteries, reflux of venous blood flow, increase in fluorescence intensity of the choroidal veins, and delayed indocyanine green dye clearance.