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Tsunehiko Ikeda,1 Masahiro Minami,1 Kimitoshi Nakamura,2 Teruyo Kida,1 Masanori Fukumoto,1 Takaki Sato,1 Eisuke Ishizaki11Department of Ophthalmology, Osaka Medical College, Osaka, Japan; 2Nakamura Eye Clinic, Nagano, JapanBackground: Nuclear sclerosis (NS) based on the Emery–Little classification and refractive values after lens-sparing vitrectomy was compared between proliferative diabetic retinopathy (DR) patients and nondiabetic patients.Methods: Progression of NS based on the Emery–Little classification and changes in refractive values were compared between 13 proliferative DR patients (14 eyes, DR group) and 14 nondiabetic patients (14 eyes, non-DR group) who underwent lens-sparing vitrectomy. All patients revealed grade I NS based on the Emery–Little classification. Mean patient age and refractive value just after surgery were 56.07 years and −0.33 diopters (D) in the DR group, and 57.06 years and −0.96 D in the non-DR group.Results: The Emery–Little classification in the DR group at 6 and 24 months postoperative were grade I (13 eyes)/grade II (one eye) and grade I (eleven eyes)/grade II (three eyes), respectively. Mean refractive values in the DR group at 6, 12, and 24 months postoperative were +0.28 D, +0.27 D, and +0.37 D, respectively. The Emery–Little classification in the non-DR group at 6 and 24 months (or preoperative for patients undergoing cataract surgery) were grade I (five eyes)/grade II (eight eyes) and grade I (zero eyes)/grade II (eight eyes)/grade III (five eyes), respectively. The mean refractive value in the non-DR group at 6 months postoperative was −3.20 D. All eyes exhibited myopic changes and progression of NS.Conclusion: The findings of this study show that the progression of NS postvitrectomy is mild, even for DR patients 50 years of age or older, thus suggesting the need to reconsider the indications for simultaneous cataract surgery with vitrectomy.Keywords: Emery–Little classification

Masanori Fukumoto, Tsunehiko Ikeda, Tetsuya Sugiyama, Mari Ueki, Takaki Sato, Eisuke Ishizaki Department of Ophthalmology, Osaka Medical College, Takatsuki City, Japan Abstract: This case report describes a case of Alagille syndrome with developing intraocular lens subluxation and rhegmatogenous retinal detachment 4 years after cataract surgery. A 15-year-old female patient with Alagille syndrome-associated cataracts in both eyes underwent phacoemulsification aspiration and intraocular lens implantation. Four years postoperative, intraocular lens subluxation developed in her left eye. For treatment, extraction of the dislocated intraocular lens, anterior vitrectomy, and intraocular lens fixation was performed. Three weeks later, the patient developed rhegmatogenous retinal detachment, which was well-treated by pars plana vitrectomy. Cataract surgery needs to be performed carefully in patients with Alagille syndrome due to the weakness of the zonule of Zinn. Careful postoperative observation is necessary for patients with Alagille syndrome who have undergone intraocular surgery in order to facilitate early detection of a possible rhegmatogenous retinal detachment. Keywords: Alagille syndrome, cataract, retina, surgery

The cases of all of the 359 inpatients seen at our hospital in one year were reviewed for cause of admission and risk factors that may have contributed to the visit. One hundred twenty-one patients were admitted due to current occlusive cerebrovascular disease (CVD). Among these 121 patients, the prevalence of hypertension in lacuna, embolism, and atherothrombosis cases were significantly higher than that of the control. There were 34 cerebral embolism cases (representing 20% of the occlusive CVD) of which the mean age (77.5 years-old) was significantly higher than those of the other subgroups of CVD. The cause of embolism was determined as cardiogenic (arrhythmia in 33 cases and post-valve replacement in one case). Arrhythmia could be broken down as follows: 19 cases were classified as continuous atrial fibrillation; 8 cases expressed paroxysmal atrial fibrillation; and 9 cases displayed sick sinus syndrome (3 cases overlap). Twenty-four of the 34 patients had had a history of treatment or realization for arrhythmia or valve replacement, however, 16 of these 24 patients had never been treated with warfarin, which resulted in current CVD. Eight patients had been treated with warfarin, however, only 2 of these 8 patients were thought to be well managed with warfarin treatment. It is now more than a decade since the effectiveness of warfarin has been proven to prevent occurrence of cerebral embolism. Every physician seems to be aware of this fact; even so, practical neglect still exists. We would like to propose and emphasize that atrial fibrillation patients should be properly managed with warfarin administration, especially elderly patients. [ABSTRACT FROM AUTHOR]

P2X 7 receptor/channels in the retinal microvasculature not only regulate vasomotor activity, but can also trigger cells in the capillaries to die. While it is known that this purinergic vasotoxicity is dependent on the transmembrane pores that form during P2X 7 activation, events linking pore formation with cell death remain uncertain. To better understand this pathophysiological process, we used YO-PRO-1 uptake, dichlorofluorescein fluorescence, perforated-patch recordings, fura-2 imaging and trypan blue dye exclusion to assess the effects of the P2X 7 agonist, benzoylbenzoyl-ATP (BzATP), on pore formation, oxidant production, ion channel activation, [Ca 2+ ] i and cell viability. Experiments demonstrated that exposure of retinal microvessels to BzATP increases capillary cell oxidants via a mechanism dependent on pore formation and the enzyme, NADPH oxidase. Indicative that oxidation plays a key role in purinergic vasotoxicity, an inhibitor of this enzyme completely prevented BzATP-induced death. We further discovered that vasotoxicity was boosted 4-fold by a pathway involving the oxidation-driven activation of hyperpolarizing K ATP channels and the resulting increase in calcium influx. Our findings revealed that the previously unappreciated pore/oxidant/K ATP channel/Ca 2+ pathway accounts for 75% of the capillary cell death triggered by sustained activation of P2X 7 receptor/channels. Elucidation of this pathway is of potential therapeutic importance since purinergic vasotoxicity may play a role in sight-threatening disorders such as diabetic retinopathy., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Purpose: Although decentralized control of blood flow is particularly important in the retina, knowledge of the functional organization of the retinal microvasculature is limited. Here, the authors characterized the distribution and regulation of L-type voltage-dependent calcium channels (VDCCs) within the most decentralized operational complex of the retinal vasculature--the feeder vessel/capillary unit--which consists of a capillary network plus the vessel linking it with a myocyte-encircled arteriole., Methods: Perforated-patch recordings, calcium-imaging, and time-lapse photography were used to assess VDCC-dependent changes in ionic currents, intracellular calcium, abluminal cell contractility, and lumen diameter, in microvascular complexes freshly isolated from the rat retina., Results: Topographical heterogeneity was found in the distribution of functional VDCCs; VDCC activity was markedly greater in feeder vessels than in capillaries. Experiments showed that this topographical distribution occurs, in large part, because of the inhibition of capillary VDCCs by a mechanism dependent on the endogenous polyamine spermine. An operational consequence of functional VDCCs predominantly located in the feeder vessels is that voltage-driven vasomotor responses are generated chiefly in this portion of the feeder vessel/capillary unit. However, early in the course of diabetes, this ability to generate voltage-driven vasomotor responses becomes profoundly impaired because of the inhibition of feeder vessel VDCCs by a spermine-dependent mechanism., Conclusions: The regulation of VDCCs by endogenous spermine not only plays a critical role in establishing the physiological organization of the feeder vessel/capillary unit, but also may contribute to dysfunction of this decentralized operational unit in the diabetic retina.

The essential task of the circulatory system is to match blood flow to local metabolic demand. However, much remains to be learned about this process. To better understand how local perfusion is regulated, we focused on the functional organization of the retinal microvasculature, which is particularly well adapted for the local control of perfusion. Here, we assessed the distribution and regulation of functional K(ATP) channels whose activation mediates the hyperpolarization induced by adenosine. Using microvascular complexes freshly isolated from the rat retina, we found a topographical heterogeneity in the distribution of functional K(ATP) channels; capillaries generate most of the K(ATP) current. The initiation of K(ATP)-induced responses in the capillaries supports the concept that the regulation of retinal perfusion is highly decentralized. Additional study revealed that microvascular K(ATP) channels are redox sensitive, with oxidants increasing their activity. Furthermore, the oxidant-mediated activation of these channels is driven by the polyamine spermine, whose catabolism produces oxidants. In addition, our observation that spermine-dependent oxidation occurs predominately in the capillaries accounts for why they generate most of the K(ATP) current detected in retinal microvascular complexes. Here, we also analysed retinal microvessels of streptozotocin-injected rats. We found that soon after the onset of diabetes, an increase in spermine-dependent oxidation at proximal microvascular sites boosts their K(ATP) current and thereby virtually eliminates the topographical heterogeneity of functional K(ATP) channels. We conclude that spermine-dependent oxidation is a previously unrecognized mechanism by which this polyamine modulates ion channels; in addition to a physiological role, spermine-dependent oxidation may also contribute to microvascular dysfunction in the diabetic retina.

Purpose: To clarify the involvement of angiotensin II-dependent vascular endothelial growth factor (VEGF) via NADPH oxidase in the retina in spontaneously diabetic Torii (SDT) rats, a type 2 diabetic rat model. In SDT rats, the plasma glucose level and angiotensin-converting enzyme (ACE) levels were measured, and effects of angiotensin II receptor blocker (ARB) and angiotensin II were also studied., Materials and Methods: We evaluated the age-dependent changes in the peripheral and ocular angiotensin II-forming systems in SDT rats at 15 (n = 8), 20 (n = 8), 30 (n = 7), and 50 weeks of age (n = 8). We also evaluated the effect of an ARB (2.5 mg/kg/day candesartan) or angiotensin II (500 ng/kg/min) on retinal gene expressions of VEGF and p22phox, a subunit of NADPH oxidase., Results: The plasma glucose level was significantly increased from 20 weeks of age. No significant changes in ACE activities in the plasma, aorta, and eye were observed until 30 weeks of age. At 50 weeks, ACE activity in the eyes was significantly increased, whereas ACE activities in the plasma and aorta were not. At 50 weeks, significant increases in VEGF and p22phox, an NADPH oxidase subunit, were significantly reduced by candesartan. Angiotensin II infusion resulted in significant increases in VEGF and p22phox levels., Conclusions: Angiotensin II is involved in the gene expression of VEGF via NADPH oxidase in the retina of SDT rats.

Magnetic resonance images (MRI) of 103 patients were examined to reveal whether positive antinuclear antibody is a risk factor for cerebral ischemia. The most common MRI formation was the presence of small high-intensity spots. The prevalence of hypertension and diabetes mellitus was significantly low. Although seven cases had no medical risk factors; they showed an abnormal MRI reading. Eleven cases exhibited signs of cerebral stroke. Positive antinuclear antibody cases are suggested to be part of the antiphospholipid antibody syndrome. Various types of cerebral arterial occlusion may occur, showing lacuna, atheroma generation, and a recurrent major vessel occlusion.

Purpose: To determine whether inflammatory reactions are involved in the pathogenesis of diabetic macular edema, we examined the relationship between diabetic macular edema and the ratio of T helper 1 (Th1) to T helper 2 (Th2) cells., Methods: Thirty-nine diabetic patients with diabetic retinopathy were evaluated at our hospital between February 2004 and February 2005. Blood samples were collected from each patient, and the ratio of CD4+ Th1 to Th2 cells (Th1/Th2) was determined by flow cytometry after fluorescent antibody staining for intracellular cytokines. Logistic regression analysis was used to determine the association of macular edema with age, gender, HbA(1c) level, interval after retinal photocoagulation and Th1/Th2 ratios. Differences in these parameters were also compared between patients with and without macular edema., Results: Logistic regression analysis showed that the Th1/Th2 ratios were significantly associated with macular edema (odds ratio = 0.838; p = 0.02), while other variables were not. The Th1/Th2 ratio was significantly lower in the patients with diabetic macular edema than in those without (p = 0.02; t test). Higher Th1/Th2 ratios tended to be associated with better visual acuity., Conclusions: Shifts in the balance of Th1/Th2 towards a predominance of Th2 may represent an exacerbating factor for diabetic macular edema, although a causal relationship has still not been definitively determined., ((c) 2008 S. Karger AG, Basel.)

Background: Senior-Loken syndrome is a rare disorder that combines juvenile nephronophthisis with retinitis pigmentosa., Methods: Case report., Results: A 9-year-old Japanese girl diagnosed with Senior-Loken syndrome subsequently developed severe Coats disease-like exudative retinopathy. Although retinal coagulation, pars plana lensectomy, and vitrectomy were performed, she lost light perception in both eyes., Conclusion: Faulty vascular morphogenesis and its dysfunction might contribute to the development of Coats disease-like exudative retinopathy in Senior-Loken syndrome.

Purpose: To investigate the involvement of angiotensin-converting enzyme (ACE) with angiogenic factors, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 in the vitreous of eyes with proliferative diabetic retinopathy (PDR)., Design: Observational case series., Methods: Angiotensin-converting enzyme activity in the vitreous was measured by using a synthetic substrate for ACE. VEGF and MMP-9 concentrations were determined by enzyme-linked immunosorbent assay., Results: Vitreous ACE activity was significantly higher in eyes with PDR (1.4 +/- 1.3 mU/ml) than in eyes with macular holes (0.22 +/- 0.11 mU/ml). Vitreous VEGF concentration in the eyes with PDR (1067 +/- 1076 pg/ml) was significantly higher than in eyes with macular holes (34 +/- 5.5 pg/ml). Vitreous MMP-9 concentration was also significantly higher in eyes with PDR (7.5 +/- 3.8 ng/ml) than in eyes with macular holes (4.2 +/- 1.4 ng/ml). Significant correlations between ACE and VEGF (P < .01) and between ACE and MMP-9 (P < .01) were observed in the vitreous of eyes with PDR., Conclusions: Angiotensin-converting enzyme was significantly correlated with angiogenic factors, VEGF and MMP-9, in the vitreous of eyes with PDR.

Background: We have analyzed the records of our own hospitalized cases of bilateral chronic subdural hematoma (cSDH) to reveal the prognosis., Methods: Ninety-eight cases of cSDH were operated at our hospital over a 6-year period, in which 14 cases were classified as being bilateral. Among these 14 cases, 6 cases showed a rapid and aggressive clinical course. Therefore, complicated risk factors, the initial data on coagulofibrinolytic examination, magnetic resonance imaging appearance, and prognosis were analyzed., Results: Of the 6 cases, 5 showed a rapid aggravation as they awaited surgery. The period of the aggravation since the initial diagnosis harboring cSDH was 19 to 54 hours. One case was at first neurologically free from any disturbance but 17 hours later experienced a generalized seizure. All 6 cases experienced consciousness disturbance. In addition, 3 of them manifested oculomotor palsy. Two cases showed an abnormality of coagulofibrinolytic activity. No significant risk factors were revealed. In 4 cases, T(2)-weighted images (T2WIs) revealed the hematoma of a mixed high and low intensity, indicating that the hematoma consisted of both liquid and solid parts of a freshly formed blood clot. In 2 cases, the hematoma showed a low intensity in T(1)-weighted image (T1WI), indicating a recent bleeding of a significant amount., Conclusion: The bilateral cases of cSDH should be treated as early as possible with simultaneous decompression of bilateral hematoma pressure, even if the patient shows minimal neurologic deficits. Mixed high and low intensity in T2WI or low intensity in T1WI is the most predictable factor to show rapid aggravation.

A 59-year-old woman visited our institute with the chief complaint of dizziness which persisted whenever she tried to focus on objects. She had not experienced apparent double vision and had no history of intracranial bleeding. Neurological examination revealed no abnormality except for exotropia at the mid-position and at upper gaze. Cerebral angiography revealed that the intracranial portion of the left internal carotid artery ran more horizontally and also identified an unruptured left internal carotid-anterior choroidal artery (IC-AChA) aneurysm of 3.0 mm diameter. The aneurysm at the origin of the AChA was confirmed during surgery. The proximal lateral wall of the aneurysm was in contact with the oculomotor nerve. This contact was released after complete obliteration of the aneurysm. The exotropia resolved 3 months later. Oculomotor nerve palsy usually indicates the presence of internal carotid-posterior communicating artery (IC-PcomA) aneurysm. Since sacrifice of the AChA will result in severe neurological deficits, accurate neuroimaging information is needed prior to the operation. Conventional angiography and/or three-dimensional computed tomography angiography should be performed to ascertain whether the aneurysm is an IC-PcomA or IC-AChA aneurysm, even if some neurosurgeons insist that conventional angiography is not always needed before surgery for an unruptured aneurysm.

Two cases of transient global amnesia (TGA) following coronary angiography are reported. Nonionic contrast media was used and injected at room temperature. Both cases showed sudden amnesia about 15 minutes after the left ventriculography. A clinical feature was typical to TGA, showing repeated questions with retrograde and antegrade memory disturbance without any other neurological abnormality. Diffusion-weighted images (DWI) of magnetic resonance imaging revealed no fresh lesion in both cases. The patients recovered from TGA attack within 24 hours. Some cases have been reported which display a manifested TGA following cerebral or coronary angiography. In these situations, embolism, the effect by the contrast media was suspected as the cause of TGA. Since most TGA cases in a classical meaning (primary TGA) showed no abnormality in both DWI and T2-weighted image (T2WI), the cerebral ischemia was not really considered to be the cause of the condition. Therefore, the pathogenesis of the TGA is suggested to be much more functional rather than anatomically abnormal. The pathogenesis of the primary TGA was thought to be some kind of hypersensitivity to the external stress or the stress reaction of the hippocampal cell. This stress may lead to cellular depolarization and the following repolarization (spreading depression), which showed transient abnormality in DWI and not a permanent abnormality in T2WI.

A case of solitary and unilateral trochlear nerve palsy following a minor, blunt head impact is reported. A 72-year-old man fell down backwards from the top of a staircase having 13 steps and hit his right parietal head and shoulder. Routine neurological examination revealed no remarkable findings, however, the subject complained of double vision when he focused downwards. The computed tomography four hours after the initial impact showed a localized small high-density lesion on the left quadrigminal cistern. The magnetic resonance imaging also indicated subarachnoid bleeding expressed by the low-intensity area in T2 weighted images in the same place. There was no evidence of any contusion within the midbrain. Hess chart test clearly showed solitary left superior oblique muscle palsy. The manner of the injury was thought to be quite typical, since he had hit his right parietal area up-side-down when falling, that is, the accelerated force acted as an impact against the firm floor. This impact caused the midbrain concussion against the cerebellar tentorial notch resulting in a localized subarachnoid hemorrhage which caused the unilateral trochlear nerve palsy.

In order to avoid confusion in categorizing malignant lesions for surgical treatment, a definition and criteria of carcinomas significantly involving the esophagogastric junction (ECJ-Ca) and those of gastric cardia less significantly involving the esophagogastric junction (eC-Ca) are proposed, devised as this study was from a practical viewpoint. A comparative analysis of carcinomas of these groups was carried out, the control group being those carcinomas situated mainly in the upper third segment of the stomach but not involving the esophagogastric junction (C-Ca). Carcinomas of these regions can be determined by the EGJ-Index (EGJ-I) calculated through the following formula: EGJ-Index = [( Length of the esophageal portion of the lesions)/(length of the of the esophageal portion + gastric portion of the lesion])x1,000. Thus lesions of these regions are easily and practically classified as follows: [I]: EGJ-Ca 250 less than or equal to EGJ-I less than or equal to 750, 59 cases; ( II]: eC-Ca 0 less than or equal to EGJ-I less than 250, 88 cases; [III]: C-Ca 0 = EGJ-I, 208 cases. We found these categories quite suitable for practical use.

Two forms of activated C1s, a subcomponent of the first component of complement, were present in preparations of C1 specifically purified from rabbit serum by affinity chromatography on IgG-Sepharose 6B and were separated by DEAE-cellulose chromatography in the presence of EDTA. These two activated C1s, designated C1s(I) and C1s(II), were indistinguishable with regard to hemolytic activity as well as C1s esterase activity, though they had different molecular weights. C1s(I) had a molecular weight of 106,000, consisting of H and L chains connected by disulfide bonds; the molecular weights of the chains were 70,000 and 36,000, respectively. On the other hand, C1s(II), with a molecular weight of 72,000, consisted of two chains each with a molecular weight of about 37,000, which were also connected by disulfide bonds. These results suggest that, in the case of rabbit C1s, the primary product of activation with C1r, C1s(I), may be susceptible to further cleavage of its H chain without any loss of C1s activity, resulting in the formation of C1s(II), though the active principle responsible for this conversion remains to be elucidated.

C1 inactivator (C1 INA) was highly purified from rabbit serum. C1 INA thus purified was a single polypeptide chain with a molecular weight of 105,000 or 140,000, as estimated by SDS-polyacrylamide gel electrophoresis or gel filtration on Sephadex G-200, respectively. It inhibited rabbit and also human C1, when the C1 activities were measured in terms of hydrolyses of acetylglycyl-L-lysine methylester, N-alpha-acetyl-L-arginine methylester and N-alpha-acetyl-L-tyrosine ethylester. These properties showed that rabbit C1 INA bears a marked structural similarity to human C1 INA. Furthermore, rabbit C1 INA was capable of inhibiting similarly both rabbit C1s and its active fragment lacking a half of the H chain of C1s, indicating that deletion of a half of the H chain did not affect the susceptibility of C1s to the inhibitory activity of C1 INA.