Features of retinal arterial macroaneurysms in patients with uveitis.

AIM: To determine the frequency and clinical characteristics of retinal arterial macroaneurysms in patients with uveitis. METHODS: A retrospective review of the clinical, photographic, and angiographic records of 1007 patients with uveitis, examined at the Osaka University Hospital uveitis clinic between January 1995 and April 2002, was performed. All of the records were examined to determine whether macroaneurysms were present, and when present, to determine the laterality, type, location, clinical course, and the presence of associated systemic and ocular diseases. RESULTS: Of the 1007 patients with uveitis, only 14 (1.4%) had macroaneurysms. 12 of these 14 patients had peripheral multifocal chorioretinitis (PMC), and five of these 12 were diagnosed with sarcoidosis and the other seven without sarcoidosis. There was only one case with sarcoidosis without PMC, and the remaining case was uveitis of unknown origin. There were 18 macroaneurysms in all cases and 17 (94.4%) were the exudative type, and the remaining one was the haemorrhagic type. Two patients had been treated for systemic hypertension but the others had no signs of systemic hypertension or cardiovascular disease. CONCLUSIONS: Macroaneurysms are not characteristically found in patients with uveitis, but the majority are found in patients with PMC. The majority of the macroaneurysms were the exudative type, and the conclusion is that patients with PMC should be carefully examined for exudative macroaneurysms.

Optical coherence tomography patterns of choroidal osteoma.

PURPOSE: To determine the optical coherence tomographic images that are commonly observed in eyes with choroidal osteoma (choroidal ossification). METHODS: Three patients with choroidal osteoma were examined by optical coherence tomography. RESULTS: We found two optical coherence tomographic patterns in the eyes with choroidal osteoma. First, multiple tracks of high refractivity were present posterior to the tumor lesion. Second, thick and irregular plate-like, high-signal intensity areas were present in the choroid in the region of the tumor. CONCLUSIONS: Optical coherence tomography can be useful in the diagnosis of choroidal osteoma.

Gas stress test for assessment of corneal endothelial function.

PURPOSE: This study was undertaken to evaluate the endothelial pump function by monitoring both corneal swelling response under hypoxia and dehydration response following hypoxia in vivo. METHODS: Humidified nitrogen gas was used to obtain corneal swelling, and humidified gas mixed with oxygen and nitrogen was used for corneal dehydration. First, in 6 young volunteers, we investigated the most suitable oxygen level for evaluating pump function by changing oxygen levels. Then, with the optimal oxygen level, we attempted to evaluate pump function in 53 normal subjects, 5 Fuchs' dystrophy patients, and 3 iridocorneal endothelial syndrome (ICE) patients. RESULTS: Swelling rate showed similar values regardless of age, but both dehydration rate and swelling rate plus dehydration rate decreased with aging. The swelling rate of 5 guttata corneas was significantly higher than that of age-matched control corneas. In contrast, dehydration rate markedly decreased in guttata corneas, while the swelling rate plus dehydration rate of guttata corneas was comparable to that of age-matched corneas. In the 3 ICE corneas, however, swelling rate, dehydration rate, and swelling rate plus dehydration rate were markedly lower than those of both the fellow corneas and the age-matched control corneas. CONCLUSION: These observations lead us to conclude that in order to evaluate pump function, it is necessary to monitor not only dehydration response following hypoxia but also swelling response under hypoxia.

Effects of penetrating keratoplasty rejection on the endothelium of the donor cornea and the recipient peripheral cornea.

PURPOSE: To determine the effects of penetrating keratoplasty rejection on the recipient endothelium. METHODS: Twenty transplanted corneas of 20 keratoconus patients were enrolled in this study. Ten of the corneas had undergone allograft rejection and the other 10 grafts had an uneventful postsurgical course. The endothelium of the donor cornea and the endothelium of the recipient peripheral cornea were evaluated by wide-field specular microscopy. RESULTS: The transplanted corneas that underwent allograft rejection showed a marked decrease in endothelial cell density not only in central donor cornea but also in the recipient peripheral cornea compared with that in the uneventful transplanted corneas. Additionally, the recipient endothelium had significant pleomorphism in the rejection group. There were no morphologic differences in the peripheral donor cornea between the control group and the rejection group. CONCLUSIONS: Our findings indicate that the recipient peripheral endothelium is also affected by allograft rejection, perhaps because of the contribution of recipient endothelium to the wound healing process after allograft rejection.

Lens epithelium-derived growth factor: effects on growth and survival of lens epithelial cells, keratinocytes, and fibroblasts.

We isolated a clone encoding a protein from a human lens epithelial cell (LEC) cDNA library with antibody (Ab) from a cataract patient and named it "lens epithelium-derived growth factor" (LEDGF). LEDGF is found to be identical to p75, a coactivator of both transcription (1) and pre-mRNA splicing (2). In serum-free medium LEDGF stimulated growth of LECs, cos7 cells, skin fibroblasts, and keratinocytes, and prolonged cell survival. Without LEDGF, the aforementioned cells did not survive. Also in serum-free medium, Ab to LEDGF neutralizing LEDGF blocked cell growth and caused cell death. Thus, LEDGF, a regulatory factor, may play an important role for growth and survival of a wide range of cell types.

Corneal endothelial changes in patients with chronic renal failure.

PURPOSE: To evaluate the morphologic changes of the corneal endothelium in patients with chronic renal failure. METHODS: Twenty corneas of 20 patients with chronic renal failure undergoing hemodialysis were examined by wide-field specular microscopy. Twenty normal corneas from 20 healthy age-matched subjects were enrolled as control corneas. RESULTS: Despite normal endothelial cell density, the corneal endothelium of patients with chronic renal failure showed marked polymegethism and pleomorphism. CONCLUSION: Polymegethism and pleomorphism of the corneal endothelium are found in patients with chronic renal failure.

Concentration dependent effects of hydrogen peroxide on lens epithelial cells.

AIMS: To evaluate the effects of hydrogen peroxide exposure on the survival and proliferation of cultured lens epithelial cells. METHODS: TOTL-86 cells, a line of rabbit lens epithelial cells, were used. The survival and proliferation of TOTL-86 cells were quantified by a rapid colorimetric assay (MTT assay). To determine the effects of hydrogen peroxide, TOTL-86 cells were exposed to different concentrations of hydrogen peroxide. To determine the effect of cell numbers on the survival and proliferation of TOTL-86 cells at a fixed concentration of hydrogen peroxide, different numbers of cells were plated and exposed to hydrogen peroxide. To determine whether there is a synergistic effect between hydrogen peroxide and EGF, bFGF, PDGF-AA, and insulin, TOTL-86 cells were exposed to hydrogen peroxide combined with one of these growth factors. RESULTS: High levels (1 mM) of hydrogen peroxide killed TOTL-86 cells and sublethal levels (100 microM) suppressed their proliferation. From 1 nM to 1 microM of hydrogen peroxide, there was a dose dependent increase in the cell numbers. The initial seeded cell number dramatically affected the response to hydrogen peroxide. Although growth factors showed no synergistic effects with hydrogen peroxide on proliferation, both EGF and insulin, but not bFGF or PDGF, rescued TOTL-86 cells from the sublethal effect. CONCLUSION: Hydrogen peroxide in cooperation with some growth factors plays an important role in the proliferation of lens epithelial cell.

Association of plasma fibrinogen level and blood pressure with diabetic retinopathy, and renal complications associated with proliferative diabetic retinopathy, in Type 2 diabetes mellitus.

AIM: To clarify the association of several clinical parameters, including plasma fibrinogen level, with diabetic retinopathy in patients with Type 2 diabetes mellitus (DM). METHODS: A total of 294 Japanese patients with Type 2DM were studied; 53 patients with no diabetic retinopathy (NDR), 90 with background diabetic retinopathy (BDR), and 151 with proliferative diabetic retinopathy (PDR). Multiple logistic regression analysis was performed to assess variables independently associated with diabetic retinopathy in two settings: presence of retinopathy of any severity and presence of advanced retinopathy. RESULTS: The following parameters were identified as independent factors associated with the presence of diabetic retinopathy (NDR vs. BDR + PDR): type of therapy (P<0.0005), log-transformed plasma fibrinogen level (P < 0.05), mean blood pressure (P < 0.05), and duration of diabetes (P < 0.05). The independent variables associated with advanced retinopathy were type of therapy (P<0.00005), age (P<0.0005) and nephropathy (P<0.05). Body mass index, smoking and hypertensive status, HbA1c and total cholesterol levels were not independently associated. CONCLUSIONS: These data suggest that in patients with Type 2 DM, an increased blood viscosity due to high fibrinogen level as well as an elevated intravessel pressure play a role in the development of diabetic retinopathy, and that the progression to PDR is influenced or accompanied by the deterioration of renal status.

Lens epithelium-derived growth factor: increased resistance to thermal and oxidative stresses.

PURPOSE: To investigate the role of lens epithelium- derived growth factor (LEDGF) in lens epithelial cells subjected to heat or oxidative stress and to determine the localization of LEDGF in lens epithelial cells at different temperatures. METHODS: Mouse lens epithelial cells overexpressing a fusion protein between a green fluorescent protein (GFP) and LEDGF (GFP-LEDGF) were cultured for up to 7 days at various temperatures or for 24 hours in the presence of hydrogen peroxide. Translocation of GFP-LEDGF in the lens epithelial cells was monitored with a fluorescence microscope. Cell survival was determined with the trypan blue dye exclusion test. Expression of heat shock proteins (Hsps) was studied with protein blot analyses using antibody probes. RESULTS: LEDGF was found in the cytosol of lens epithelial cells at 4 degrees C, 15 degrees C, and 28 degrees C, and in the nucleus and nucleolus at 37 degrees C. At 41 C, it was apparent at higher levels in the cytosol, nucleus, and nucleolus. Lens epithelial cells overexpressing LEDGF manifested resistance to thermal and oxidative stress. Levels of Hsp 27, and alphaB-crystallin were elevated in these cells. Depriving lens epithelial cells of LEDGF with anti-LEDGF antibodies reduced nuclear localization of LEDGF and induced cell death. CONCLUSIONS: The overexpression of LEDGF in lens epithelial cells conferred resistance to thermal and oxidative stress. The mechanism of this resistance appears to involve the increased expression of Hsp 27 and alphaB-crystallin.

[A case of retinal detachment in Kniest dysplasia treated with vitreous surgery].

We report a case of retinal detachment with Kniest dysplasia for which vitreous surgery was effective. The patient was a 7-year-old female who had the typical ocular and physical findings of this disease. Visual acuity was light perception alone due to a hypermature cataract and bullous retinal detachment. We performed cataract surgery and pars plana vitrectomy, and used silicone oil tamponade. After seven months, the silicone oil was removed, and visual acuity improved to 0.09. We conclude that bullous retinal detachment with Kniest dysplasia can be treated by vitreous surgery in combination with the use of silicone oil tamponade.

Effects of posterior chamber lens implantation on the endothelium of transplanted corneas.

AIMS: The morphological changes of the corneal endothelium after posterior chamber lens implantation in the transplanted corneas were investigated. METHODS: 36 patients underwent extracapsular cataract extraction with posterior chamber lens implantation. Among these, penetrating keratoplasty had been performed in 18 patients before cataract surgery. The indications for penetrating keratoplasty in these cases included keratoconus, herpetic keratitis, and macula cornea. 18 cataract patients with normal corneas were also studied as controls. The central corneal endothelium in each subject was examined with a wide field specular microscope at a few days before and 3 months after cataract surgery. RESULTS: Although the transplanted corneas showed lower endothelial cell densities, marked polymegethism, and pleomorphism in the baseline variables, the endothelial morphological changes in the transplanted corneas after posterior chamber lens implantation were comparable with those in the normal corneas. Also, there was no clinical evidence, especially, of corneal epithelial and/or endothelial rejections and corneal decompensation in all corneas. CONCLUSION: Even though the transplanted corneas have a lower endothelial cell density and marked polymegethism, it is believed that cataract surgery does not induce corneal decompensation in cases where the peripheral recipient endothelium can be considered to have normal morphology.

Topical aldose reductase inhibitor for correcting corneal endothelial changes in diabetic patients.

BACKGROUND: Marked variations in cell size (polymegethism) and shape (pleomorphism) are characteristic of the corneal endothelium in diabetic patients and animals. METHOD: Wide field specular microscopy was used to evaluate the clinical efficacy of treating the diabetic corneal endothelium with topical instillation of 0.5% aldose reductase inhibitor, CT-112. RESULTS: Morphological variations (polymegethism and pleomorphism) of the endothelium in eight eyes from eight patients receiving CT-112 resolved within 3 months after initiation of treatment. In contrast, no change in endothelial morphology was noted in five eyes from five patients who received placebo. CONCLUSION: These observations suggest that aldose reductase may be involved in the aetiology of corneal endothelial variations in diabetic patients.

The effects of denatured sodium hyaluronate on the corneal endothelium in cats.

In an in vivo cat model, wide-field specular microscopy and scanning electron microscopy were used to observe whether heat-denatured sodium hyaluronate causes cell damage to the corneal endothelium. The endothelial cell toxicities of various drugs, including 0.01% benzalkonium chloride, 0.2% chlorhexidine digluconate, and 0.5% lidocaine, mixed with intact or untreated sodium hyaluronate were also investigated. Neither heat-denatured nor intact or untreated sodium hyaluronate alone had any adverse effect on the corneal endothelium in cats, whereas 0.01% benzalkonium chloride and 0.2% chlorhexidine digluconate, mixed with sodium hyaluronate, caused substantial endothelial morphologic changes, which resulted in corneal edema. By comparison, 0.5% lidocaine with sodium hyaluronate was found to have minimal effect on the corneal endothelium in cats. These findings indicate that some chemical contaminant with sodium hyaluronate, not heat-denatured sodium hyaluronate, induces an immediate onset of pseudophakic bullous keratopathy.

Comparison of the effects of intraocular irrigating solutions on the corneal endothelium in intraocular lens implantation.

We conducted a randomised prospective controlled study to determine the effects of a glucose glutathione bicarbonate solution (BSS Plus) and a citrate acetate bicarbonate solution (S-MA2) on the corneal endothelium in patients undergoing extracapsular cataract extraction with posterior chamber lens implantation. One eye of each patient was randomly assigned to receive BSS Plus, and the other eye to receive S-MA2. BSS Plus caused significantly less corneal swelling on the first postoperative day than did S-MA2. There was no difference between the two solutions in their effect on corneal thickness one week and one month postoperatively. Computer assisted morphometric analysis of wide-field specular microscopic photographs demonstrated minimal changes in endothelial morphological characteristics in the eyes irrigated with BSS Plus. By comparison S-MA2, caused a significant loss of endothelial cells and a marked reduction in the figure coefficient. These results indicated that BSS Plus has a clinical advantage over S-MA2 with respect to the corneal endothelium.

Relationship of corneal endothelial morphology to diabetic retinopathy, duration of diabetes and glycemic control.

Using specular microscopy and computer-assisted morphometry, the morphologic features of the corneal endothelium were evaluated in three groups of patients with type II diabetes mellitus: 20 patients without diabetic retinopathy, 24 with background retinopathy, and 26 with proliferative retinopathy. When compared to age-matched nondiabetic controls (30 patients), all diabetic groups had similar endothelial cell densities but demonstrated significant increases in cell size and shape variability (pleomorphism). However, there was no significant difference in the degree of these endothelial changes among the three diabetic groups. Moreover, none of the endothelial morphologic parameters was found to correlate with the duration of diabetes or glycemic control, as estimated from glycosylated hemoglobin (HbA1) concentrations.