Kunihiko Shiraki

Frequency of choroidal abnormalities in neurofibromatosis type 1

BACKGROUND Choroidal neurofibromatosis is thought to be a rare form of neurofibromatosis that involves the eyes. The development of infrared light examination with a scanning laser ophthalmoscope (SLO) and indocyanine-green fundus angiography has allowed examination of the choroid. We studied choroidal abnormalities in patients with neurofibromatosis 1 and compared their frequency with that of other ocular abnormalities. METHODS We examined 33 eyes of 17 consecutive patients diagnosed with neurofibromatosis 1 by conventional ophthalmoscopy and by non-invasive infrared monochromatic light with confocal SLO. 76 eyes of 39 age-matched controls were examined similarly by confocal SLO. 21 digital fluorescein and indocyanine-green angiographies were obtained from 11 adult patients, and 77 angiograms were obtained from age-matched controls. FINDINGS Infrared monochromatic light examination by confocal SLO showed bright multiple patchy regions at and around the entire posterior pole of all 33 eyes examined. All bright patchy regions seen in adult patients corresponded to hypofluorescent areas on their indocyanine-green angiograms. However, no abnormalities were noted in any patient at corresponding areas under conventional ophthalmoscopic examination or fluorescein angiography. In SLO and indocyanine-green studies, controls and control angiograms showed no choroidal abnormalities. Iris nodules were noted in 25 eyes (76%) of 14 patients (82%) and eyelid neurofibroma in five patients (29%). INTERPRETATION The bright patchy regions noted under infrared fundus examination and the corresponding hypofluorescent areas seen on indocyanine-green angiograms are probably of choroidal origin. The high frequency (100%) of these abnormalities suggests that the choroid is one of the structures most commonly affected by neurofibromatosis 1.

Surgical Procedure for Correcting Globe Dislocation in Highly Myopic Strabismus

PURPOSE To design a surgical procedure for correcting globe dislocation in strabismus in high myopia (highly myopic strabismus). DESIGN Prospective, interventional case series. METHODS We examined 36 eyes of 21 patients with highly myopic strabismus and 27 eyes of 27 healthy volunteers as controls at Osaka City General Hospital between 2000 and 2006. Anatomic relationships between the muscle cone and globe were analyzed using magnetic resonance imaging. Ranges of globe movement and angles of ocular deviation were measured quantitatively as angles of maximum abduction and sursumduction and angles of ocular deviation, respectively, using the Goldmann perimeter and alternate prism cover tests. A surgical procedure involving muscle union of the superior rectus and lateral rectus muscles was performed in 23 eyes of 14 patients to restore the dislocated globe back to the muscle cone. RESULTS After surgery, the angle of dislocation of the globe, defined as the angle formed by a line connecting the area centroid of the superior rectus muscle and the globe and a line connecting area centroid of the lateral rectus muscle and globe against the supertemporal wall of the orbit, was significantly decreased (P < .001), and angles of maximum abduction and sursumduction and the angle of ocular deviation improved significantly (P < .001). CONCLUSIONS This surgical procedure to restore the dislocated globe back into the muscle cone by uniting muscle bellies of the superior rectus and lateral rectus muscles is effective for highly myopic strabismus.

Relation between office intraocular pressure and 24-hour intraocular pressure in patients with primary open-angle glaucoma treated with a combination of topical antiglaucoma eye drops.

PurposeTo determine the relation between office intraocular pressure (IOP) and 24-hour IOP in patients with primary open-angle glaucoma (POAG) treated with 3 kinds of antiglaucoma eye drops. Patients and MethodsSubjects were 42 patients with POAG (71 eyes). All were being treated with 3 different topical antiglaucoma eye drops (latanoprost, β-blocker, and carbonic anhydrase inhibitor). Twenty-four-hour IOP values were obtained in the sitting position with a Goldmann applanation tonometer at 3-hour intervals. ResultsMaximum 24-hour IOP (mean±SD) was 19.76±5.65 mm Hg, minimum 24-hour IOP was 13.06±4.75 mm Hg, mean 24-hour IOP was 16.30±4.90 mm Hg, and 24-hour IOP fluctuation was 6.70±2.81 mm Hg. Office IOP was 16.23±4.58 mm Hg, and office IOP fluctuation was 2.75±1.68 mm Hg. There was no significant difference between office IOP and mean 24-hour IOP (P=0.93). There was no correlation between office IOP and 24-hour IOP fluctuation (r=0.15; P=0.25) or between office IOP fluctuation and 24-hour IOP fluctuation (r=0.19; P=0.17). Maximum 24-hour IOP occurred during office hours in 22 eyes (33.8%). The frequency of maximum 24-hour IOP occurring during office hours was significantly less than that of minimum 24-hour IOP (P<0.001). ConclusionsIn POAG patients treated with 3 kinds of antiglaucoma eye drops, office IOP was similar to mean 24-hour IOP. However, it was difficult to estimate 24-hour IOP fluctuation and maximum 24-hour IOP on the basis of office IOP.

Hepatocyte growth factor stimulates proliferation and migration during wound healing of retinal pigment epithelial cells in vitro

PURPOSE A defect in retinal pigment epithelial (RPE) cells may cause dysfunction of the neural retina, so rapid recovery of differentiated RPE cells is required after RPE injury. We investigated the effect of hepatocyte growth factor (HGF) on wound healing in RPE cells. METHODS Confluent monolayers of bovine RPE cells were denuded, and the cells were allowed to recover in the presence or absence of HGF. The effect of HGF on RPE cell proliferation was evaluated by a 3-(4;5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay. In a migration assay, mitomycin C was used to inhibit proliferation, and the number of migrated cells was counted. The signaling pathways involved were examined using inhibitors of mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 (PI3) kinase and protein kinase C pathways. RESULTS At 80 ng/mL, HGF stimulated the wound closure of RPE monolayers and rendered the restituted cells more epithelioid in shape. HGF at 10 ng/mL stimulated RPE cell migration the most, whereas 80 ng/mL of HGF inhibited migration, but stimulated proliferation the most. In particular, PI3 kinase and MAPK inhibitor inhibited PRE cell migration and proliferation, respectively. CONCLUSIONS HGF stimulated wound closure in cultured RPE cells, and rendered restituted cells epithelioid in shape. HGF may become a therapeutic candidate for RPE wound healing.

Retinal sensitivity measurement over drusen using scanning laser ophthalmoscope microperimetry.

Abstract · Background: Retinal sensitivity over drusen was examined using a scanning laser ophthalmoscope to confirm a previous report of no change in sensitivity over drusen. · Methods: Microperimetry was performed using a scanning laser ophthalmoscope in 23 eyes of 19 subjects. Subject age ranged from 42 to 86 years (mean 68.5 years). Fifty-four drusen bigger than the diameter of a major retinal vein at the optic disc rim were examined, and drusen were classified as soft drusen and other large drusen. · Results: Nine eyes of eight subjects showed a decrease in retinal sensitivity over drusen. The decrease in retinal sensitivity was more than 5 dB less than the sensitivity at a peripheral non-drusen area peripheral to the measurement point. The sensitivity decrease was noted over 15 of 29 large drusen and the decrease was statistically significant (P<0.02). However, no relationship between the size of the drusen and the amount by which sensitivity decreased was found. Nevertheless, a decrease in retinal sensitivity was not seen over any of 25 soft drusen. · Conclusion: Large drusen may influence retinal sensitivity and function.

Long-term follow-up of severe central serous chorioretinopathy using indocyanine green angiography

Background: The severe types of central serous chorioretinopathy (CSC) have a chronic nature, suggesting that a pathological process persists subclinically. Indocyanine green(ICG) angiography recently revealed intrachoroidal dye leakage and its static nature in CSC. As the intrachoroidal dye leakage was suspected to be relevant to the disease process, the long-term persistence of intrachoroidal ICG leakage was examined in four patients of the severe types of CSC. Methods: ICG angiography was performed periodically over more than three years in three patients and two years in one patient. One patient had CSC with bullous retinal detachment, and the other three had chronic CSC or diffuse retinal pigment epitheliopathy. Results: Intrachoroidal ICG leakage persisted in all the patients. However, a change in location of persistent intrachoroidal leakage or disappearance of intrachoroidal leakage regardless of no progression of retinal pigment epithelial alteration was noted in one eye of two patients. Conclusions:Pathology causing intrachoroidal ICG leakage persisted subclinically for a long period. However, location and extent of the intrachoroidal leakage could change during along-term follow-up period.

The rate of symptomatic improvement of congenital nasolacrimal duct obstruction in Japanese infants treated with conservative management during the 1st year of age

This study aimed to examine the rate of symptomatic improvement of congenital nasolacrimal duct obstruction (CNLDO) in Japanese infants treated with conservative management within the 1st year of age. Thirty-five lacrimal ducts in 27 patients diagnosed with CNLDO were included in the study. During the observational period, lacrimal ducts were massaged. As well, antibiotic eye drops, to be administered 4 times a day, were sometimes prescribed for obvious conjunctivitis. Two lacrimal ducts in 2 patients were probed before the 1st year of age because of dacryocystitis or severe blepharitis; these patients were included in the unimproved group. Twenty-nine lacrimal ducts in 21 patients resolved during the period (82.9%); with 16 lacrimal ducts resolving before six months of age. Therefore, a comparatively high percentage of resolution for CNLDO (82.9%) following conservative management was shown before the 1st year of age in Japanese infants.

Assessment of the predictive value of intraoperative eyelid height measurements in sitting and supine positions during blepharoptosis repair.

Purpose: To examine relationships between intraoperative and postoperative eyelid heights in relation to patient postures in blepharoptosis surgery. Methods: Thirty eyelids in 15 patients with bilateral aponeurotic ptosis were selected. The margin reflex distance-1 (MRD-1) was measured with the patients in the sitting position preoperatively, intraoperatively, and in the postoperative 6 weeks. MRD-1 also was measured intraoperatively with patients in the supine position. The intraoperative sitting and supine values and the postoperative values were statistically compared using a paired t test, and lateralities in those groups were statistically analyzed using Students t test. Results: From the intraoperative measurements, mean MRD-1 values in the sitting position (right: 3.80 mm, left: 3.73 mm) were significantly lower than those in the supine position (right: 4.37 mm, p < 0.001; left: 4.33 mm, p < 0.001). In the postoperative 6 weeks, mean MRD-1 values (right: 3.80 mm, left: 3.63 mm) were not significantly different from intraoperative values in the sitting position (right: p = 1.000, left: p = 0.189), but were significantly lower than intraoperative values in the supine position (right: p < 0.001, left: p < 0.001). There was no significant laterality among the three groups (supine intraoperative: p = 0.890, sitting intraoperative: p = 0.785, postoperative: p = 0.546). Conclusion: Intraoperative measurements in the sitting position more accurately predicted postoperative eyelid height than did measurements with the patient in a supine position.

Fundus autofluorescence in patients with pseudoxanthoma elasticum.

Purpose: To characterize changes in fundus autofluorescence in patientswith pseudoxanthoma elasticum (PXE). Fundus autofluorescence intrinsicallyderives from lipofuscin, and the degree of autofluorescence is thought to indicatethe degree of retinal pigment epithelium (RPE) metabolic activity. Methods:Twelve eyes of 6 patients (2 men, 4 women) with PXE were studied with aconfocal scanning laser ophthalmoscope. Patient age ranged from 42 to 62years. The autofluorescence of abnormal retinal areas was compared digitallywith that of neighboring, presumed healthy control areas. When the averagegray level of a fundus region was 2 SDs above or below the average graylevel of a control area, autofluorescence of the fundus region was consideredabnormal. Results: In all 12 eyes, some segments of the angioid streaksshowed decreased fundus autofluorescence, and other segments of the streaksshowed normal autofluorescence. Areas of peripapillary chorioretinal atrophyseen in 2 eyes and of disciform scarring seen in 3 eyes showed decreasedautofluorescence. Solitary or multiple drusen-like spots showed increasedautofluorescence in all 12 eyes. Conclusion: Atrophic and degenerativeRPE regions showed decreased fundus autofluorescence in areas of chorioretinalatrophy and in some segments of the angioid streaks. Some drusen-like spotsshowed increased autofluorescence. The characteristic changes in autofluorescencethat we observed in PXE patients suggest that the content of the drusen-like substancediffers from that of senile drusen and that the drusen-like lesions are similar to thesub-RPE deposits seen in macular dystrophy.

Effect of Retinoic Acid on Proliferation and Polyamine Metabolism in Cultured Bovine Retinal Pigment Epithelial Cells

Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 µM RA significantly increased both cell number and [3H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N1-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N1-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.