Protein kinase C beta inhibitor prevents diabetic peripheral neuropathy, but not histopathological abnormalities of retina in Spontaneously Diabetic Torii rat.

Spontaneously Diabetic Torii (SDT) rat shows severe ocular complications such as tractional retinal detachment. In the present study, effect of protein kinase C beta (PKCbeta) inhibitor JTT-010 was evaluated to clarify the involvement of PKCbeta in complications of SDT rat. SDT rats were administered JTT-010 (10 or 50 mg/kg/day) for 48 weeks. SDT rats showed delayed oscillatory potentials in electroretinogram. Delayed motor nerve conduction velocity, decreased coefficients of variation of R-R intervals in electrocardiogram and thermal hypoalgesia were also observed. These functional disorders were prevented by administration of JTT-010. Abnormal retinal vascular was formed and the optic disc was protruded in SDT rat; however, JTT-010 did not prevent these hyperglycaemia-induced retinal abnormalities. These findings indicate that PKCbeta is intimately involved in diabetic complications; however, it seems that other factor(s) are primary contributors to histopathological abnormalities in retina. Therefore, PKCbeta inhibitors require concurrent administration of antihyperglycaemic drugs to achieve maximum effect on diabetic complications.

Diabetic macular edema-like ocular lesions in male spontaneously diabetic torii fatty rats.

Diabetic macular edema (DME) is a major factor contributing to visual disabilities in diabetic patients, and the number of patients is increasing. Animal models play a key role in the development of novel therapies. In this study, pathophysiological analyses of ocular lesions in Spontaneously Diabetic Torii (SDT) fatty rats were performed. First, vascular endothelial growth factor (VEGF) concentrations in vitreous humor, retinal vascular permeability and retinal thickness were measured in SDT fatty rats (Experiment 1). Furthermore, the pharmacological effects of two anti-diabetic drugs, phlorizin and pioglitazone, on retinal lesions were evaluated (Experiment 2). As results, the SDT fatty rats exhibited VEGF increase in vitreous humor at 8 and 16 weeks of age, and both retinal vascular hyperpermeability and retinal thickening at 16 weeks of age. In particular, the layers between the retinal internal limiting membrane and the outer nuclear layer were thickened. Phlorizin treatment from 4 to 16 weeks of age improved hyperglycemia and normalized retinal thickness; however, the effect of pioglitazone on retinal thickness was not strong despite the normalization of hyperglycemia. These data demonstrate that the male SDT fatty rat is a useful model for developing new therapeutic approaches in DME.

Nicorandil improves diabetes and rat islet beta-cell damage induced by streptozotocin in vivo and in vitro.

OBJECTIVE: N-(2-hydroxyethyl)-nicotinamide nitrate (nicorandil) is a unique anti-anginal agent, reported to act as both an ATP-sensitive K(+) channel opener (PCO) and a nitric oxide donor. It also has an anti-oxidant action. We examined the effects of nicorandil on streptozotocin (STZ)-induced islet beta-cell damage both in vivo and in vitro. DESIGN AND METHODS: STZ-induced diabetic Brown Norway rats (STZ-DM) were fed with nicorandil-containing chow from day 2 (STZ-DM-N48), 3 (STZ-DM-N72), and 4 (STZ-DM-N96) to day 30. Body weight, blood glucose, and plasma insulin were measured every week. For the in vitro assay, neonatal rat islet-rich cultures were performed and cells were treated with nicorandil from 1 h before to 2 h after exposure to STZ for 30 min. Insulin secretion from islet cells was assayed after an additional 24 h of culture. We also observed the effect of nicorandil on the generation of reactive oxygen species (ROS) from rat inslinoma cells (RINm5F). RESULTS: Body weight loss and blood glucose levels of STZ-DM-N48 rats were significantly lower than those of STZ-DM rats. Immunohistochemical staining of insulin showed preservation of insulin-secreting islet beta-cells in STZ-DM-N48 rats. Nicorandil also dose-dependently recovered the insulin release from neonatal rat islet cells treated with STZ in in vitro experiments. Nicorandil did not act as a PCO on neonatal rat islet beta-cells or RINm5F cells, and did not show an inhibitory effect on poly(ADP-ribose) polymerase-1. However, the drug inhibited the production of ROS stimulated by high glucose (22.0 mmol/l) in RINm5F cells. CONCLUSIONS: These results suggested that nicorandil improves diabetes and rat islet beta-cell damage induced by STZ in vivo and in vitro. It protects islet beta-cells, at least partly, via a radical scavenging effect.

Vitreous photography with a +90-diopter double aspheric preset lens vs the El Bayadi-Kajiura preset lens.

Two fundus lenses, a 90-diopter preset lens and a 58.6-diopter El Bayadi-Kajiura lens, were compared. The lenses were evaluated with regard to their optics, magnification, field of view, and photographic usefulness in photographing the posterior vitreous. The 90-diopter lens provided a wider field of view but lower magnification. Both lenses permitted high-quality vitreous photographs through the slit lamp, but the 90-diopter lens allowed photographs to be taken through small pupils and some lens opacities.

Predictive value of floaters in the diagnosis of posterior vitreous detachment.

PURPOSE: To evaluate Weiss ring and floaters as indexes of posterior vitreous detachment. METHODS: Using biomicroscopy and indirect ophthalmoscopy, we examined the posterior vitreous in 200 consecutive eyes with posterior vitreous detachment. RESULTS: In 200 eyes with posterior vitreous detachment, biomicroscopy disclosed complete, incomplete, and no Weiss ring in 102 (51%), 72 (36%), and 26 (13%) eyes, respectively. Indirect ophthalmoscopy showed the glial ring in 58 (56.9%) and 16 (22.2%) of the eyes, with a complete (102 eyes) and incomplete (72 eyes) Weiss ring, respectively. Although the incidence of floaters was significantly correlated with the presence of the glial ring (P = .0014), 60 (58.8%) and 49 (68.1%) of the eyes with a complete (102 eyes) and incomplete (72 eyes) glial ring, respectively, had no floaters. CONCLUSION: Detecting the detached posterior vitreous cortex by biomicroscopy is essential regardless of the presence of Weiss ring or floaters.

Vitreous findings in cases of optic nerve pits and serous macular detachment.

We examined biomicroscopically the relationship between the optic nerve and the vitreous in 17 eyes of 16 consecutive patients with pits of the optic nerve that demonstrated an associated serous detachment of the macula. The posterior vitreous was attached in 15 eyes (88%); the posterior vitreous was partially detached with a vitreous strand terminating at the optic pit in two eyes (12%). Of the 15 eyes without posterior vitreous detachment, 11 (73%) had an anomalous Cloquet's canal that was markedly condensed and terminated at the margin of the pit. During ocular movement, we observed a back-and-forth movement of the anomalous Cloquet's canal and a pulsating translucent membrane that covered the pit. Our findings suggest that the intravitreal traction on the optic pit by the anomalous Cloquet's canal may have a role in the development of macular detachment.

Spontaneous resolution of foveal detachments and macular breaks.

PURPOSE: To evaluate the mechanism of spontaneous resolution of foveal detachments and idiopathic macular breaks. METHODS: We reviewed the records of 139 consecutive eyes (94 patients) with either a foveal detachment or a macular break in patients who were examined between 1989 and 1992. There were 26 men and 68 women (mean age, 66.9 +/- 6.9 years). They were either unoperated on or observed during the period that preceded surgery. Each patient underwent complete ophthalmic examination in addition to slit-lamp photography of the vitreomacular interface and microperimetry with the scanning laser ophthalmoscope. RESULTS: Eight eyes demonstrated spontaneous resolution. A foveal detachment was noted in five eyes (five patients) and a stage 2 macular break in three eyes (three patients). The mean duration of observation was 33 months (range, one to 144 months). Resolution of the foveal detachments occurred without the development of posterior vitreous detachment. In each eye, the presence of a pseudo-operculum, indicating vitreofoveal separation, was accompanied by flattening of the foveal detachment without detectable posterior vitreous detachment. The three eyes with stage 2 macular break resolved after premature development of a posterior vitreous detachment. CONCLUSIONS: Foveal detachment and macular break resolution seem to result from the release or weakening of vitreous traction on the fovea. Reattachment of the foveal retina preserves fair to good visual acuity. Surgical intervention is contraindicated (1) in eyes in which foveal detachment flattens and develops a pseudo-operculum and (2) when a posterior vitreous detachment develops in an eye with a stage 2 macular break. Careful biomicroscopic vitreous examination and microperimetry with the scanning laser ophthalmoscope are extremely useful methods for adequate examination of these patients.

Variations of posterior vitreous detachment.

AIMS: To identify variations in posterior vitreous detachment (PVD) and establish a clinical classification system for PVD. METHODS: 400 consecutive eyes were examined using biomicroscopy and vitreous photography and classified the PVD variations-complete PVD with collapse, complete PVD without collapse, partial PVD with thickened posterior vitreous cortex (TPVC), or partial PVD without TPVC. RESULTS: In each PVD type, the most frequently seen ocular pathologies were as follows: in complete PVD with collapse (186 eyes), age related changes without vitreoretinal diseases (77 eyes, 41.4%) and high myopia (55 eyes, 29.6%); in complete PVD without collapse (39 eyes), uveitis (23 eyes, 59.0%) and central retinal vein occlusions (8 eyes, 20.5%); in partial PVD with TPVC (64 eyes), proliferative diabetic retinopathy (30 eyes, 46.9%); and inpartial PVD without TPVC (111 eyes), age related changes without vitreoretinal diseases (62 eyes, 55.9%). This PVD categorisation was significantly associated with the prevalence of each vitreoretinal disease (p < 0.0001, chi 2 test on contingency table). CONCLUSIONS: PVD variations can be classified into four types, which is clinically useful because each type corresponds well to specific vitreoretinal changes.

A new form of retinopathy associated with myocardial infarction treated with percutaneous coronary intervention.

AIM: To report a new form of retinopathy that was observed in patients who had undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (AMI). METHODS: Serial ophthalmological examinations were conducted in 40 patients who underwent PCI. Thirty patients were diagnosed with AMI, and another 10 had stable angina pectoris. RESULTS: Cotton wool spots developed in 17 (57%) patients from the group with AMI undergoing PCI (n = 30) within 2 months. Of these, 41% (seven patients) also developed superficial haemorrhages. Retinopathy was most prominent 1-2 months after AMI and then tended to become quiescent afterwards, without treatment. CONCLUSION: We have identified a new form of retinopathy in patients with AMI that spontaneously subsides without treatment.

Differential diagnosis of macular breaks by microperimetry using the scanning laser ophthalmoscope.

To improve the differential diagnosis of macular breaks by microperimetry using the scanning laser ophthalmoscope (SLO), we studied 50 consecutive breaks detected by biomicroscopy and indirect ophthalmoscopy. The full-thickness macular break was easily diagnosed using only biomicroscopy and indirect ophthalmoscopy because the macular break had a cuff in 22 of the eyes. SLO microperimetry also showed an absolute scotoma within the macular break and a relative scotoma on the cuff in these 22 eyes. However, in the other 28 eyes it was impossible to distinguish between the full-thickness macular breaks and pseudo-macular breaks or lamellar macular breaks using only biomicroscopy and indirect ophthalmoscopy because of the absence of a cuff. However, SLO microperimetry differentiated full-thickness macular breaks from pseudomacular breaks or lamellar macular breaks in these 28 eyes. SLO microperimetry is indispensable for determining the prognosis of and the surgical indication requirements for idiopathic macular breaks.

Clinical characteristics of traumatic macular holes.

The clinical characteristics of 20 eyes of 20 consecutive patients with traumatic macular hole were studied retrospectively. The macular holes were elliptical with irregular edges in 19 eyes (95%) and ranged in size from 0.2 to 0.5 DD (disc diameter). Posterior vitreous detachment (PVD) was found in only 3 eyes (15%); the vitreous was detached from the macula in only one of these 3. Other conditions found in the 20 patients included commotio retinae, vitreous hemorrhage, hyphema, and choroidal rupture. These findings strongly suggest that most traumatic macular holes develop in the absence of PVD and that the pathogenesis is independent of the occurrence of PVD. We believe that the macular rupture (hole) is caused mechanically by the force of the impact on the posterior pole and the ocular deformity which result from blunt trauma.

Vitreous videography using the scanning laser ophthalmoscope.

To establish the method of vitreous videography using the scanning laser ophthalmoscope, we observed the vitreous in patients with age- or disease-related vitreous changes. We compared the results using four laser wavelengths. The detailed structures of the posterior vitreous cortex, a premacular defect, and a prepapillary glial ring were clearly shown under direct laser illumination. A short wavelength laser was found to be superior to a long wavelength laser for observing the posterior vitreous cortex. Vitreous opacities were clearly shown as dark spots under retroillumination using any of the four laser wavelengths. In vivo visualization of the vitreous was achieved using this new technique, which is superior to conventional biomicroscopy because of its monochromatic laser delivery system and confocal light detection capacity.

Abnormal vitreous structure in optic nerve pit.

A 37-year-old man presented with an optic nerve pit and serous macular detachment of the left eye. Scanning laser ophthalmoscopy revealed a cyst-like structure terminating at the pit in the premacular vitreous. During ocular movement, this structure moved vigorously and seemed to exert traction on the pit. We believe that it is part of an anomalous Cloquet's canal, and that traction on the pit may be a significant factor in the development of serous macular detachment in this patient.

[Biomicroscopic findings of premacular posterior vitreous].

The presence of vitreous gel in front of the macular area is still controversial. In order to understand the anatomy of the premacular vitreous, the posterior vitreous was observed biomicroscopically and slit-lamp photographs were taken in 100 eyes without posterior vitreous detachment. We defined the premacular vitreous as the lacuna seen when optically empty space, a demarcated oval shaped dark area without Tyndall phenomenon, was observed in front of the macula. Although the premacular vitreous showed liquefaction, the Tyndall-phenomenon, indicating the presence of formed vitreous gel, was observed in most cases. Premacular lacuna was observed in 3 cases with high myopia, and in one case with vitreoretinal degeneration syndrome. The bursa premacularis or premacular precortical vitreous pocket observed in autopsy eyes could barely be observed in living eyes.

[Observing idiopathic macular break by scanning laser ophthalmoscope vitreous videography].

We used vitreous videography in conjunction with the scanning laser ophthalmoscope (SLO) to evaluate the pathogenesis of idiopathic macular breaks. The fundamental aspect of this method is videographic documentation of the mobile posterior vitreous and an operculum. The high reflectivity from the vitreous gel using the SLO clearly showed the mobility of the operculum and the posterior vitreous in the idiopathic macular breaks. In some cases without posterior vitreous detachment, the operculum initially was suspended superior to the macular break and anterior to the retinal surface. Upon ocular movement, the operculum moved down smoothly in front of the macular break. The findings of these vitreous videographs using the SLO suggest that anteriorly oriented vitreous traction is one cause of idiopathic macular breaks.

[Differential diagnosis of macular breaks by microperimetry with a scanning laser ophthalmoscope].

To improve differential diagnosis of macular breaks, microperimetry with a scanning laser ophthalmoscope (SLO) was performed. Fifty consecutive macular breaks were detected by biomicroscopy and indirect ophthalmoscopy, and SLO microperimetry was performed on each. Of the 50 eyes, 22 eyes were diagnosed with idiopathic macular breaks by biopmicroscopy and indirect ophthalmoscopy because of a cuff. SLO microperimetry also showed dense scotoma within the macular break and relative scotoma on the cuff in the 22 eyes. However, diagnosis was not done only by biomicroscopy and indirect ophthalmoscopy in the other 28 eyes because of the absence of a cuff. SLO microperimetry differentiated the full thickness macular breaks from pseudo-or lamellar breaks in these eyes. SLO microperimetry is useful for differentiating their prognosis, and determining the need for surgical treatment.

[Vitreous videography with a scanning laser ophthalmoscope].

We used a scanning laser ophthalmoscope (SLO) to attempt better visualization of the posterior vitreous than conventional biomicroscopy. We observed the posterior vitreous using the SLO in patients with age- or disease-related vitreous changes. We compared the results using lasers of several wavelengths. The detailed structure of the posterior hyaloid membrane, its collagen mesh structure with premacular defect, and the prepapillary glial ring were clearly visualized by direct laser illumination. Persistent attachment of the vitreous gel to the macula through the oval defect in the posterior hyaloid membrane was seen even with repeated eye rotations. Short wavelength laser was preferable to a long wavelength one for observing the posterior hyaloid membrane. Vitreous opacities were clearly visualized with all lasers as dark spots with fundus monitoring by retro illumination. Thus in vivo visualization of the posterior hyaloid membrane and vitreous gel was achieved using this new technique, which is more advantageous than the conventional biomicroscopy because of its monochromatic laser delivery system with confocal light detection.

[Traumatic macular hole and posterior vitreous].

We studied retrospectively the clinical features of 18 eyes of 18 patients with traumatic macular hole. The macular hole was elliptical with irregular edges in 17 eyes (94%) and its size ranged from 1/5 to 1/2 of the disc diameter. Posterior vitreous detachment was found in 3 eyes (17%); the vitreous was detached from the macula in only one of these 3 eyes. Commotio retinae, vitreous hemorrhage, hyphema, or choroidal rupture was also found in several eyes. These findings suggest that traumatic macular hole develops usually in the absence of posterior vitreous detachment and its pathogenesis is independent of the occurrence of posterior vitreous detachment. We speculate that blunt trauma-induced deformity of the eyeball or impact on the posterior pole provides a mechanical cause for the macular rupture.