Shinki Chin

Reduction of Intraocular Pressure Using a Modified 360-degree Suture Trabeculotomy Technique in Primary and Secondary Open-Angle Glaucoma: A Pilot Study

PurposeTo investigate the effects of a modified 360-degree suture trabeculotomy technique for primary and secondary open-angle glaucoma (POAG and SOAG). MethodsWe modified the procedure for 360-degree trabeculotomy by using a 5-0 nylon suture, making a scleral flap to allow clear identification of Schlemm canal, and creating a corneal side port incision opposite to the scleral flap to retrieve the suture used to cannulate and cleave the canal. The modified 360-degree suture trabeculotomy (not combined with cataract surgery) was performed on 25 eyes with POAG and 18 eyes with SOAG, and the results were compared retrospectively with those of standard trabeculotomy with metal trabeculotomes (16 eyes with POAG and 19 eyes with SOAG). When the intraocular pressure (IOP) was reduced by 30% from the preoperative IOP and was also below 18 mm Hg at 3, 6, 9, 12, and 18 months after surgery and the patient was taking a similar number or fewer medications, the surgery was considered a “success.” ResultsUsing this modified technique, Schlemm canal was appropriately incised without resistance. At 12 months after the modified 360-degree suture trabeculotomy and trabeculotomy with metal trabeculotomes, the mean postoperative IOP values were 13.1 and 15.2 mm Hg, respectively, and the mean numbers of antiglaucoma medications were 0.5 and 1.4, respectively. The success rates of POAG at 12 months for the modified 360-degree suture trabeculotomy and trabeculotomy with metal trabeculotomes were 84% and 31%, respectively, and those of SOAG were 89% and 50%, respectively. The complications included a transient elevation of the IOP above 30 mm Hg in 22 eyes (47%) treated with the 360-degree suture trabeculotomy and 17 eyes (49%) treated with trabeculotomy with metal trabeculotomes. There was no significant difference between preoperative visual acuity and postoperative visual acuity in either procedure. ConclusionsThis modified 360-degree suture trabeculotomy is a feasible surgical option for POAG and SOAG.

Simple-spike activity of floccular Purkinje cells responding to sinusoidal vertical rotation and optokinetic stimuli in alert cats.

To understand how the cerebellar flocculus is involved in the processing of semicircular canal signals in the vertical vestibulo-ocular reflex (VOR), we analyzed the simple-spike activity of floccular Purkinje (P) cells that was modulated by sinusoidal pitch rotation, and then analyzed their activity during presentation of sinusoidal vertical optokinetic stimuli in alert, head-fixed cats. The great majority of P cells also responded to optokinetic stimuli with peak discharge near peak stimulus velocity. Eighty percent of P cells that responded to both pitch and optokinetic stimuli showed increased activity when the directions of the resultant eye movements were the same. During rapid modification of the VOR induced by visual pattern movement, modulation amplitudes of the cells tested increased together with the eye velocity increase. Maximal activation directions of these cells studied during vertical rotation in many planes were near the vertical canal planes, similar to those in our previous studies. The remaining 20% of P cells showed increased discharge for the same direction of stimulus movement. These results suggest that the activity of the majority of pitch-responding P cells contains, at least partly, a vertical eye velocity component during presentation of vestibular or optokinetic stimuli in addition to canal inputs during pitch rotation.

Chapter 32 Further evidence for the specific involvement of the flocculus in the vertical vestibulo-ocular reflex (VOR)

We examined the simple-spike activity of floccular Purkinje (P) cells during sinusoidal pitch rotation and vertical optokinetic stimuli in alert, head-fixed cats. The great majority of pitch-responding P cells also responded to optokinetic stimuli with increased activity when the directions of the resultant eye movements were the same. During rapid modification of the VOR induced by visual pattern movement, modulation amplitudes of the cells tested increased together with the eye velocity increase. Maximal activation directions of these cells studied during vertical rotation in many planes were near the vertical canal planes. These results suggest that the activity of the majority of pitch-responding P cells contains a vertical eye velocity component during vestibular or optokinetic stimuli in addition to canal inputs during pitch rotation.

Ocular tilt reaction with vertical eye movement palsy caused by localized unilateral midbrain lesion.

A 60-year-old man developed diplopia and experienced difficulty moving his eyes. Vertical movement of each eye, including vestibulo-ocular reflex and smooth pursuit, was extremely limited. Horizontal eye movements were normal. His head position was tilted toward his left. There was 10 prism diopters of exotropia and 10 prism diopters of right hypertropia. Fundus photographs revealed a clockwise torsion of both eyes. These signs indicate leftward ocular tilt reaction. Magnetic resonance imaging showed a small area of an increased signal intensity localized in the midbrain dorsomedial to the red nucleus on the right side. Based on recent experimental evidence, it may be assumed that the unilateral lesion involving the right interstitial nucleus of Cajal most probably caused leftward ocular tilt reaction in our patient.

Association study of genetic variants on chromosome 7q31 with susceptibility to normal tension glaucoma in a Japanese population

The caveolin 1 to caveolin 2 (CAV1–CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1–CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms; that is, rs1052990, rs4236601, and rs7795356, in the CAV1–CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1–CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1–CAV2 region to the development of glaucoma.

Mydriasis with Light-Near Dissociation in Fisher's Syndrome

BackgroundApproximately 50% of patients with Fishers syndrome show involvement of the pupillomotor fibers and present with mydriasis and light-near dissociation. However, it is uncertain whether this phenomenon is induced by an aberrant reinnervation mechanism as in tonic pupil, or is based on other mechanisms such as those associated with tectal pupils.CasesWe evaluated the clinical course and the pupillary responses in four of 27 patients with Fishers syndrome who presented with bilateral mydriasis.ObservationsThe pupils of both eyes of the four patients were involved at the early stage of Fishers syndrome. The pupils in patients 1 and 2 showed mydriasis with apparent light-near dissociation lasting for a significant period and had denervation supersensitivity to cholinergic agents. On the other hand, the pupils of patients 3 and 4 were dilated and fixed to both light and near stimuli.ConclusionsOur observations indicate that the denervated iris sphincter muscles, which are supersensitive to the cholinergic transmitter, may play an important role in the expression of light-near dissociation in Fishers syndrome. Jpn J Ophthalmol 2007;51:224–227

A Case of Neuroretinitis Associated with Long-Standing Polyarteritis nodosa

We reported a 45-year-old man suffering from neuroretinitis with long-standing polyarteritis nodosa and anterior uveitis. Fluorescein angiography, made at the stage when optic disk swelling developed, demonstrated a hypofluorescent area at the temporal part of the optic disc presenting exudates in its prelaminar region. When the swelling of the optic disc had resolved as verified ophthalmoscopically, and the hypofluorescence was angiographically undetectable, a macular star was observed, showing a configuration corresponding to Henles layer.

Ocular motor disorders in mitochondrial encephalopathy with lactic acid and stroke-like episodes with the 3271 (T-C) point mutation in mitochondrial DNA.

Background: Ocular motor function can provide insights into areas of dysfunction within the nervous system. There are no published eye movement recordings in patients with mitochondrial encephalopathy with lactic acid and stroke-like episodes (MELAS). Our purpose in this study was to analyze the ocular motor features of a family with MELAS with a (T-C) mutation at nucleotide position 3271 in the mitochondrial tRNA-Leu gene. Methods: The search coil method was used to record visually-guided saccades, antisaccades, and triangular pursuit tasks in the horizontal and vertical planes in three patients in a Japanese family with MELAS. Results: The patients showed saccadic dysmetria and prolonged saccadic reaction times, deficits in the ability to suppress reflex eye movements, and increased reaction time during antisaccades, downbeat nystagmus, square wave jerks, and impairment in pursuit. Conclusions: On the basis of eye movement recordings, patients with MELAS have frontal cortex as well as cerebellar dysfunction.

Ocular torsion produced by unilateral chemical inactivation of the cerebellar flocculus in alert cats.

Purpose. Vertical eye movements are executed by the vertical recti and oblique muscle pairs. Since each of these pairs rotates the eye in both vertical and torsional directions, torsional components must be controlled to execute appropriate, purely vertical eye movements. To test whether the cerebellar flocculus is involved in the control of torsional eye position, we examined the effects of unilateral chemical inactivation of the flocculus on ocular torsion in alert cats. Methods. Pitch-responding floccular regions were first identified, then the GABA agonist muscimol was injected unilaterally into the identified regions. Ocular torsion was examined photographically. Results. Unilateral muscimol infusion into pitch-responding areas in the rostral and middle parts of the flocculus resulted in significant intorsion of the eye ipsilateral to the infusion. Gaze-holding was also impaired following downward saccades induced by visual stimuli. Although the contralateral eye showed a tendency towards extorsion, the effects were not significant. Muscimol infusion into the caudal flocculus did not induce consistent effects on ocular torsion. Conclusion. The cerebellar flocculus plays a key role in the maintenance of torsional eye position.

Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma

Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies, and lowering intraocular pressure is associated with an attenuation of progressive optic nerve damage. Nevertheless, intraocular pressure (IOP) reduction alone was not enough to inhibit the progression of disease, which suggests the contribution of other factors to the glaucoma pathogenesis. In this study, we investigated the cytoprotective effect of geranylgeranylacetone (GGA) on RGCs degeneration using a normal tension glaucoma (NTG) mouse model, which lacks glutamate/aspartate transporter (GLAST) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure (IOP). Three-week-old GLAST+/− mice were given oral administration of GGA at 100, 300, or 600 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. At 5 weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. In addition, retrograde labeling technique was also used to quantify the number of RGC. Expression and localization of heat shock protein 70 (HSP70) in retinas were evaluated by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Activities of caspase-9 and -3 in retinas were also assessed. The number of RGCs of GLAST+/− mice significantly decreased, as compared to that of control mice. RGC loss was significantly suppressed by administration of GGA at 600 mg/kg/day, compared with vehicle alone. Following GGA administration, HSP70 was significantly upregulated together with reduction in the activities of caspase-9 and -3. Our studies highlight HSP70 induction in the retina is available to suppress RGC degeneration, and thus GGA may be applicable for NTG as a promising therapy.