Novel mutations in the RS1 gene in Japanese patients with X-linked congenital retinoschisis.

X-linked congenital retinoschisis (XLRS) is an inherited retinal disorder characterized by reduced central vision and schisis of the macula and peripheral retina. XLRS is caused by mutations in the RS1 gene. We have identified 37 different mutations in the RS1 gene, including 12 novel mutations, in 67 Japanese patients from 56 XLRS families. We present clinical features of these patients in relation to the associated mutations.

Effect of oral tranexamic acid on macular edema associated with retinal vein occlusion or diabetes.

PURPOSE: Tranexamic acid (TXA) is a widely used antifibrinolytic agent that can also cause a decrease in vascular permeability. We hypothesized that TXA could improve macular edema (ME) that is caused by an increase in retinal vascular permeability. The aim of this study is to evaluate the efficacy of oral TXA for ME associated with retinal vein occlusion (RVO) or diabetic ME (DME). PATIENTS AND METHODS: Oral TXA (1,500 mg daily for 2 weeks) was administered to patients with persistent ME secondary to RVO (7 eyes) and DME (7 eyes). After 2 weeks (ie, the final day of administration) and 6 weeks (ie, 4 weeks after the final administration), best-corrected visual acuity and central macular thickness (CMT) were measured and compared with baseline. Analyses were performed for RVO and DME cases. No other treatment was performed during the study period. RESULTS: In RVO cases, significant improvement in CMT was found between baseline (467.7±121.4 µm) and 2-week measurements after treatment (428.7±110.5 µm, p=0.024). No significant change was found in CMT between measurements taken at baseline and 6 weeks after treatment. In DME cases, no significant change was found in CMT between measurements taken at baseline and 2 or 6 weeks after treatment. In all analyses of best-corrected visual acuity, no significant change was observed. CONCLUSION: The results support the hypothesis that plasmin plays a role in the development of ME associated with RVO, and oral TXA administration may be useful as an adjuvant treatment when combined with other agents such as anti-vascular endothelial growth factor.

Ocular parameters before and after steep Trendelenburg positioning for robotic-assisted laparoscopic radical prostatectomy.

PURPOSE: Intraocular pressure (IOP) increases in patients in a steep Trendelenburg position during robotic-assisted laparoscopic radical prostatectomy (RALP). We hypothesized that a steep Trendelenburg position during RALP, an unusual systemic condition involving a transiently increased IOP, may induce ocular pathology that can be detected by detailed evaluations long after the surgery. This study aims to explore ocular structural and functional parameters in patients before and in the long term after the surgery. PATIENTS AND METHODS: A comparative observational study was performed. A total of 44 eyes of 22 male patients scheduled for RALP at Aichi Medical University from August 2012 to July 2013 were included. Clinical parameters before and after RALP were compared. Perioperative IOP was measured immediately post-induction of anesthesia in the flat supine position (T1), immediately post-steep Trendelenburg position (T2), and prior to returning to a flat supine position while in a steep Trendelenburg position (T3). The thicknesses of the peripapillary retinal nerve fiber layer, ganglion cell complex (GCC), and central fovea were measured with spectral domain optical coherence tomography. Humphrey perimetry was performed before and at 3 and 6 months after surgery. RESULTS: The average IOPs (mmHg) at each stage were T1=10.4, T2=21.7, and T3=29.6, and differed significantly. The mean visual acuity (logarithm of the minimal angle of resolution), IOP, mean deviation, and pattern standard deviation measured by the Humphrey field analyzer showed no statistically significant difference before and after surgery. The ganglion cell complex and retinal nerve fiber layer thicknesses measured at each location and the central fovea thicknesses measured before and after surgery did not differ significantly. CONCLUSION: No significant disorders in ocular structural and functional parameters were found until long after RALP.

Decreased VEGF-A and sustained PEDF expression in a human retinal pigment epithelium cell line cultured under hypothermia.

BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD) after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A) and in vitro angiogenesis in retinal pigment epithelium (RPE). RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31 °C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF). We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.

Late-onset toxic anterior segment syndrome.

UNLABELLED: We describe 6 cases that developed intraocular inflammation between 42 days and 137 days after implantation of an acrylic foldable intraocular lens (IOL) (ISert model 251) and failed to respond to antibiotic treatment. One eye required a vitrectomy and IOL removal, 2 eyes required irrigation of the capsule, and 5 eyes required systemic administration of steroids. The healing process took 30 to 108 days after onset. Simultaneous with our cases was an epidemic outbreak of sterile anterior segment inflammation with the same characteristics associated with the same IOL. The clinical features indicated late-onset toxic anterior segment syndrome. Analysis of the outbreak strongly suggested that toxicity of the aluminum used in the IOL production process was the cause. This contamination risk exists even with modern manufacturing technology. FINANCIAL DISCLOSURE: Mr. Shibuya is an employee of Hoya Corporation Medical Division. No other author has a financial or proprietary interest in any material or method mentioned.

Decreased VEGF-A and sustained PEDF expression in a human retinal pigment epithelium cell line cultured under hypothermia

BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD) after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A) and in vitro angiogen-esis in retinal pigment epithelium (RPE). RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31°C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF). We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.

Long-term progressive deterioration of visual function after papilledema improved by embolization of a dural arteriovenous fistula in the sigmoid sinus: a case report.

INTRODUCTION: It is generally believed that people affected by papilledema will not have progressive damage to their eyesight if they receive adequate medical care to treat the underlying cause of the papilledema. We present a case that appears to contradict this widely accepted belief. CASE PRESENTATION: A 53-year-old Japanese man with tinnitus visited our hospital. His initial best-corrected visual acuity in either eye was not impaired, although they both exhibited papilledema. Magnetic resonance imaging did not reveal a mass or hemorrhagic lesion in our patient's brain. Nevertheless, his best-corrected visual acuity gradually deteriorated over the following three months. Angiography demonstrated a dural arteriovenous fistula in his sigmoid sinus. After embolization therapy, the papilledema improved in both eyes. However, over the subsequent four years, his best-corrected visual acuity progressively deteriorated due to an unknown cause, despite the successful embolization of the dural arteriovenous fistula. CONCLUSION: There may be delayed onset of an unknown pathophysiology in the visual system after treatment for the underlying cause of papilledema, implying an uncertain visual prognosis for patients with this condition.

Effects of topical diquafosol pretreatment on intraoperative corneal wetting.

PURPOSE: To examine the effects of pretreatment with diquafosol 3.0% ophthalmic solution on corneal surface wetting during cataract surgery with intraocular lens (IOL) implantation in cases of senile cataract. SETTING: Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, Japan. DESIGN: Prospective randomized single-masked comparative study. METHODS: Phacoemulsification and IOL implantation were performed in eyes with senile cataract. After a 2-week washout period, patients were randomly assigned to receive 1 drop of diquafosol 3.0% ophthalmic solution or artificial tears 6 times daily for 4 weeks before surgery. The main outcome measure, termed the corneal wetting property, was the time between when a clear image of the operating microscope light source appeared just after the corneal surface was irrigated with a balanced salt solution and the time at which that image began to blur. RESULTS: The study enrolled 51 patients (76 eyes). The mean time to corneal wetting was 50.1 seconds ± 10.8 (SD) in the diquafosol group and 45.3 ± 9.2 seconds in the artificial tears group. The difference between the 2 groups was statistically significant (P<.029). CONCLUSION: Four-week pretreatment with diquafosol 3.0% ophthalmic solution in patients with senile cataract scheduled for cataract surgery with IOL implantation was effective in enhancing the intraoperative corneal surface wetting property, which suggests improved optical clarity during surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Recurrent vitreous hemorrhage associated with regressed retinopathy of prematurity in a 47-year-old patient: a case report.

INTRODUCTION: Vitreous hemorrhage associated with retinopathy of prematurity is often seen in childhood, but adult onset without retinal break is rare. We describe a case of recurrent vitreous hemorrhage associated with regressed retinopathy of prematurity in a 47-year-old patient. CASE PRESENTATION: A 47-year-old Japanese woman with a history of retinopathy of prematurity presented with a visual disturbance in her left eye due to vitreous hemorrhage. Because the vitreous hemorrhage was recurrent and refractory, we performed pars plana vitrectomy combined with lens extraction by phacoemulsification and intraocular lens implantation. No retinal break or retinal detachment was found. No vitreous hemorrhage or other complication occurred in the first six months after surgery. CONCLUSIONS: Vitrectomy, potentially in combination with lens extraction, should be considered in adult-onset recurrent vitreous hemorrhage associated with retinopathy of prematurity.

Macroaneurysm on the optic disc in a patient with aortic dissection.

PURPOSE: We report a case of macroaneurysm on the optic disc, a rare location, accompanied by vitreous hemorrhage in a patient with aortic dissection. METHODS: A 60-year-old female with a history of aortic dissection at the age of 51 presented with visual disturbance owing to vitreous hemorrhage in her right eye. During vitrectomy, we found a large macroaneurysm on the optic disc that was beating and oozing blood. However, the macroaneurysm was not treated. RESULTS: The macroaneurysm gradually shrunk, and the beating and oozing of blood disappeared accordingly. CONCLUSION: Up to now, there have been no reports of macroaneurysm on the optic disc in aortic dissection patients. The association between macroaneurysm on the optic disc and aortic dissection is unclear; therefore, additional case reports may be necessary. To the best of our knowledge, our case is the first one reported in the literature.

Infliximab counteracts tumor necrosis factor-α-enhanced induction of matrix metalloproteinases that degrade claudin and occludin in non-pigmented ciliary epithelium.

Infliximab, a monoclonal antibody directed against human tumor necrosis factor-alpha (TNF-α), effectively treats anterior uveitis, which can accompany Behçet's disease. Here, we investigated the underlying mechanism of this action. We examined human, non-pigmented ciliary epithelial cells (HNPCECs), which make up the blood-aqueous barrier (BAB) in the uvea. We measured the expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the presence or absence of TNF-α using quantitative, real-time polymerase chain reaction and enzyme-linked immunosorbent assays. The expression of MMP-1, MMP-3, and MMP-9 increased in the presence of TNF-α, and the addition of infliximab reversed the increase. The TNF-α effects were more attenuated when infliximab was added before than when it was added after TNF-α exposure. Gelatin zymography demonstrated that the protease activity of these MMPs was also increased in the presence of TNF-α and attenuated with infliximab. Immunostaining showed that MMP-1, MMP-3, and MMP-9 degraded claudin-1 and occludin in HNPCECs and in non-pigmented ciliary epithelial cells of the swine ciliary body. In a monolayer of HNPCECs, we found that permeability was significantly increased with MMP treatment. Thus, TNF-α increased levels of MMPs in cells that form the BAB, and MMPs degraded components of the tight junctions in the BAB, which increased permeability through the cellular barrier. Furthermore, infliximab effectively attenuated the TNF-α-induced increases in MMP expression in cells that make up the BAB. These findings might suggest a basis for the clinical prevention of anterior uveitis.

The narrowest part of the bony nasolacrimal canal: an anatomical study.

PURPOSE: To determine the narrowest diameter of the bony nasolacrimal canal. METHODS: Fifty-eight bony nasolacrimal canals from 29 Japanese cadavers (12 men and 17 women; average age at death, 83.4 years; range, 70-99 years) had been fixed in 10% buffered formalin before use. After exposing the medial (44 canals) or posterior half (14 canals) of the bony nasolacrimal canal, the part with the shortest anteroposterior or transverse diameter was determined on inspection. These positions from the canal entrance were measured, and the distance ratio, indicating where the shortest diameter was located in relation to the total length of the canal, was calculated. RESULTS: The shortest anteroposterior and transverse diameters were at the entrance to the canal in 32 of 44 canals (72.7%) and in 9 of 14 canals (64.3%), respectively. In the other canals, the shortest anteroposterior and transverse diameters were located at an average of 3.6 and 5.6 mm from the entrance, and the distance ratios were 29.0% and 46.7%, respectively. The mean shortest anteroposterior and transverse diameters were 5.6 and 5.6 mm, respectively. CONCLUSIONS: The shortest anteroposterior and transverse diameters were at the entrance of the canal in most of the bony nasolacrimal canals. These results are comparable with the rate of obstruction at the canal entrance in primary acquired nasolacrimal duct obstruction.

Dacryoendoscopic findings of intracanalicular punctal plug migration with or without canaliculitis.

An 83-year-old woman with Sjögren syndrome underwent insertion of large punctal plugs in the right upper and lower puncti. Nine months later, she presented with upper canaliculitis, although the plugs were not found in the puncti. Dacryoendoscopic examination revealed punctal plug migration, granulation, and a large amount of debris in the upper canaliculus. The plug was situated parallel to the canaliculus, occluding the intracanalicular space. The lower canaliculus also showed plug migration, but little granulation and debris were present. The plug was situated perpendicular to the intracanalicular space, securing a space around the plug. The migrated plugs were pushed directly toward the nasal cavity by the dacryoendoscope. Curettage was performed in the upper canaliculi. Bicanalicular silicone intubation was performed, and removal was performed 3 months later. The patient remained symptom-free for 6 months postoperatively.

Horizontal orientation of the bony lacrimal passage: an anatomical study.

PURPOSE: To examine the horizontal orientation of the bony lacrimal passage. METHODS: The orbits and bony nasolacrimal canals (BNLCs) from 28 Japanese cadavers (11 men and 17 women; average age at death, 83.6 years; range, 70-99 years) were fixed and exenterated before use. After exposing the posterior halves of the lacrimal fossa (LF) and the BNLC, the authors measured the angles of the longitudinal axes of the LF and the BNLC relative to the sagittal line. Based on these values, the relative horizontal orientation of the LF and the BNLC was determined (ΔBNLC-LF). Positive angles of LF and BNLC were defined when the LF and BNLC were directed laterally against the sagittal line. A positive ΔBNLC-LF was defined as having a greater angle for the LF than for the BNLC. RESULTS: The mean LF and BNLC angles, and the ΔBNLC-LF were 11.9°, 0.1°, and 11.8°, respectively. The LF inclined laterally against the sagittal plane for all sides and the BNLC ran almost parallel to sagittal plane on average. The BNLC inclined inward against the sagittal line (0° or negative BNLC angle) for 28 sides (50.0%) and inclined outward (positive BNLC angle) for 28 sides (50.0%). The angle of the LF in women was statistically greater than that in men, though no gender BNLC angle or ΔBNLC-LF differences were determined. CONCLUSIONS: The horizontal angle of the bony lacrimal passage differs among individuals, with an equal split between medial and lateral inclinations of the BNLC with reference to the sagittal line.

No histological evidence of orbicularis oculi muscle hypertrophy in congenital epiblepharon.

BACKGROUND: To analyse the microscopic anatomy of the orbicularis oculi muscle in patients with congenital epiblepharon and to determine whether hypertrophy of the orbicularis oculi muscle, which is considered as a possible cause of this eyelid malposition, exists. METHODS: Sixty-seven eyelids with congenital epiblepharon of 41 Japanese patients, as well as 30 control eyelids of 24 Japanese patients with other eyelid pathologies (upper eyelid: fourteen blepharoptosis, one trichiasis and two retractions; lower eyelid: five involutional entropions, one trichiasis and seven retractions) were analysed. These controls contained no orbicularis pathology such as cicatrization or orbitopathy. The muscle specimens were obtained from the central part of the pretarsal orbicularis oculi muscle during surgery. The specimens were stained with haematoxylin & eosin. Only specimens with cross-sectional areas that included large muscle fibres were selected. In each section, 10 muscle fibres were measured across their smallest diameter, thereby avoiding inaccurate measurements of muscle kinking occurring during the processing or by any obliquity of the plane of section. Measurements of the muscle fibre diameter were made with a digital measure. RESULTS: There were no significant differences in the average diameter of the muscle fibres between the patients with congenital epiblepharon and the control group. CONCLUSIONS: There was no evidence of orbicularis oculi muscle hypertrophy in congenital epiblepharon.

Inferior oblique muscle origin: horizontal location in relation to ala nasi and its gender difference.

We studied the horizontal location of the inferior oblique muscle (IOM) origin in relation to the ipsilateral ala nasi and compared the results between genders in 76 orbits of 38 Japanese cadavers. Consequently, the IOM origin was located 1.2 mm laterally to the vertical line through the lateral margin of the ipsilateral ala nasi. No significant difference was noted between genders (males, 1.3 mm; females, 0.9 mm; P = 0.257, Student t test) or between sides (right, 1.1 mm; left, 1.3 mm; P = 0.570, Student t test). In contrast, the mean interalae-nasi distance was 39.8 mm and was significantly greater in males than that in females (males, 40.8 mm; females, 38.6 mm; P = 0.049, Student t test). The ala nasi can be used as a reference point irrespective of gender or side for identifying the IOM origin during oculoplastic surgery.

Comparative analysis of hyaluronan's affinity for antivascular endothelial growth factor agents.

BACKGROUND: Differences in the efficacy of bevacizumab, an antivascular endothelial growth factor (VEGF) agent, against retinopathy with neovascularization when injected into the vitreous cavity of vitrectomized and nonvitrectomized eyes suggests the involvement of hyaluronan, a major component of the vitreous body. This study aimed to compare the affinities of hyaluronan for anti-VEGF agents in vitro. METHODS: We examined the affinities of hyaluronan for 3 anti-VEGF agents (bevacizumab, pegaptanib and ranibizumab). Tritium [(3)H]-labeled hyaluronan was incubated separately with each anti-VEGF agent. The ratio of bound and unbound hyaluronan measured using solid and liquid phase methods was calculated. RESULTS: Hyaluronan demonstrated a significantly greater affinity for bevacizumab than for pegaptanib or ranibizumab. CONCLUSIONS: The absence or presence of hyaluronan may be associated with the clinical efficacy of bevacizumab injected into the vitreous cavity due to the affinity of hyaluronan for bevacizumab.

The orientation of the lacrimal fossa to the bony nasolacrimal canal: an anatomical study.

PURPOSE: To examine the relative positions of the lacrimal fossa (LF) and the bony nasolacrimal canal (BNLC) in relation to each other and a reference plane. METHODS: Forty-two orbits and BNLCs from 21 Asian cadavers (9 men and 12 women; average age at death, 84.4 years; range, 70-99 years) had been fixed in 10% buffered formalin before use. After exposing the LF and the medial half of the BNLC, the authors measured the angles of the longitudinal axis of the LF and the BNLC relative to the aesthetic horizontal plane respectively. Based on these values, the relative orientation of the LF and the BNLC was determined and defined in terms of Δ BNLC-LF. A positive Δ BNLC-LF represents a nasolacrimal canal that descends posteriorly relative to the LF. RESULTS: The mean LF, BNLC, and Δ BNLC-LF were 9.5°, 19.8°, and 10.3°, respectively. In 39 passages (92.9%), the Δ BNLC-LF was positive, representing a nasolacrimal canal that is more posteriorly oriented than the LF. In 3 passages (7.1%), the Δ BNLC-LF was equal to or less than 0°; 2 of them (4.8%) had a straight course and 1 passage (2.4%) had a negative value. CONCLUSIONS: In most patients, the BNLC is directed more posteriorly than the LF. This finding may help in preventing an inadvertent false passage during probing and intubation in patients with epiphora.

The causative factors or characteristics of the Asian double eyelid: an anatomic study.

PURPOSE: To clarify the causative factor of Asian double eyelid. DESIGN: Experimental anatomic study. PARTICIPANTS: Twenty-six upper eyelids (13 right and 13 left) from 17 Japanese cadavers (9 males and 8 females, mean age at death: 73.1 years). METHODS: The specimens, obtained from the central part of the upper eyelids, were dehydrated, embedded in paraffin, cut into 7-µm thick slices and stained with Masson trichrome. Statistical analysis was based on the Mann-Whitney U test. Statistical significance was defined as p < 0.05. MAIN OUTCOME MEASURES: Orbicularis oculi muscle thickness and shape, with or without the levator extension, orbicularis oculi muscle bundle spacing, thickness of upper eyelid skin and subcutaneous tissue, fusional site between the levator aponeurosis and the orbital septum, with or without inferior drooping of fat tissue. RESULTS: The orbicularis muscle was thinner at the skin crease of a double eyelid than at 10 mm from the eyelid margin in the single eyelid group (p = 0.029). In 3 specimens the skin crease of double eyelid was at the tip of the bending orbicularis muscle, which was thick. Although the skin crease in the region of a double eyelid was thinner than in other parts of the skin, excluding the simple crease regions, other outcome measures were not shown as definite causative factors in creating the Asian double eyelid. CONCLUSIONS: The thickness of orbicularis oculi muscle or its bending shape, and the thickness of the skin at the skin crease, are major causative factors in Asian double eyelid formation.

Preaponeurotic fat advancement for prevention of unexpected higher eyelid crease in upper eyelid-lengthening surgery.

PURPOSE: To present a modified technique based on preaponeurotic fat advancement for preventing higher eyelid crease in upper eyelid-lengthening surgery. METHODS: Outcomes of Japanese patients with Graves' orbitopathy-related upper eyelid retraction who underwent transcutaneous upper eyelid-lengthening surgery were reviewed. The minimum follow-up period was 6 months. A total of 17 upper eyelids in 11 patients (average age, 38.4 years) were included. After confirming appropriate upper eyelid lowering with good contour, preaponeurotic fat was fully exposed and fixed on the upper tarsal plate 1 mm superior to the planned eyelid crease with 5 sutures. Skin-tarsus-skin sutures were placed to create an eyelid crease and close the skin. Simple suture tarsorrhaphy was performed with 2 sutures. RESULTS: No upper eyelids demonstrated higher eyelid crease postsurgically. Upper eyelid fullness caused by the advanced preaponeurotic fat was not conspicuous. CONCLUSIONS: Our technique is a countermeasure against higher eyelid crease in upper eyelid-lengthening surgery.