Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

ASYMMETRIC CONE DISTRIBUTION AND ITS CLINICAL APPEARANCE IN RETINITIS PIGMENTOSA.

PURPOSE: To report the characteristic changes of fundus autofluorescence in the nasal retina of patients with retinitis pigmentosa. METHODS: We investigated 113 eyes of 113 patients with retinitis pigmentosa. We obtained wide-field fundus autofluorescence images and evaluated the status of the retina nasal to the optic disk. The patients were divided into the following three groups: those without nasal sparing (advanced), those with nasal sparing, and those with larger intact areas in addition to the nasal retina (early). Visual acuity, visual field area, age, and the duration of the symptom were compared among the groups. RESULTS: Twenty eyes (17.7%), 51 (45.1%), and 42 (37.1%) were classified as early, nasal sparing, and advanced, respectively. The nasal retina was essentially preserved in the early group. The clinical characteristics' analysis suggested that the disease progression appears from that represented by early groups, then nasal sparing groups, and finally advanced groups. The authors found that the nasal sparing pattern bears a close resemblance to the previously reported cone photoreceptor distribution. CONCLUSION: Wide-field fundus autofluorescence imaging detected nasal sparing in retinitis pigmentosa. The characteristic fundus autofluorescence pattern should reflect cone photoreceptor distribution in the human retina. This finding may be an example of the clinical appearance of asymmetric photoreceptor distribution.

Transconjunctival sutureless intrascleral intraocular lens fixation using intrascleral tunnels guided with catheter and 30-gauge needles.

We invented a new method for fixing an intraocular lens (IOL) in the scleral tunnel without using a wide conjunctival incision. Modified bent catheter needles were used to penetrate the IOL haptics through the sclerotomy sites. The IOL haptics were inserted into 30-guage (G) scleral tunnels guided by double 30-G needles piercing the sclera. All procedures were performed through the conjunctiva without wide incision. The procedure does not require special forceps, trocars or fibrin glue, only catheter and 30-G needles. The aid of an assistant was not required to support the IOL haptic. The procedures were easily learnt based on our previous method. As with other transconjunctival sutureless surgeries, patients feel less discomfort and the conjunctiva can be conserved for future glaucoma surgery. Complications included two cases of vitreous haemorrhage (16.7%), and one case each of postoperative hypotony, and iris capture (8.3%). Astigmatism induced by intraocular aberration was the same as we reported previously. Our method for fixing the IOL into the scleral tunnel is innovative, less expensive, less invasive and quick. This modified method is a good alternative for fixing IOL haptics into the sclera.

Intrascleral fixation technique using catheter needles and 30-gauge ultrathin needles: lock-and-lead technique.

UNLABELLED: We report a new intrascleral fixation technique for a standard 3-piece posterior intraocular lens (IOL) using catheter needles and 30-gauge ultrathin needles instead of a special forceps and minimal intraocular manipulation in eyes without capsule support. Modified catheter needles are used to deliver the IOL haptic. The IOL haptic is secured extraocularly between the cannula and needle of a catheter needle and then advanced through the sclerotomy site. Scleral tunnels are created using 30-gauge ultrathin needles, which also serve as a guide to introduce the haptics. This technique can be performed even in cases in which miosis and corneal edema prevent anterior chamber observation. The guide needle facilitates haptic insertion into the long and narrow scleral tunnels. The procedure is a good alternative to current techniques. FINANCIAL DISCLOSURE: Dr. Akimoto is a consultant to Kowa Co., Ltd. No other author has a financial or proprietary interest in any material or method mentioned.

Association of retinal vessel attenuation with visual function in eyes with retinitis pigmentosa.

PURPOSE: To investigate the association between visual changes and retinal vessel attenuation in patients with retinitis pigmentosa (RP). DESIGN: A retrospective, longitudinal, observational cohort study. METHODS: We analyzed 45 eyes from 45 subjects who were followed-up for ≥3 years at our clinic. Using the computer-based Interactive Vessel Analysis program, central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were determined. Age- and sex-matched controls from normal subjects were selected from our archived fundus photograph library. Visual acuity, visual field area (Goldmann perimetry, V4e white test light), mean deviation (Humphrey perimetry, central 10-2 program), and central macular thickness (optical coherence tomography) were analyzed for correlations with CRAE and CRVE. RESULTS: Both CRAE and CRVE were significantly decreased in RP eyes (94.9±13.5 µm and 155.6±20.0 µm, respectively) compared with control eyes (138.1±14.7 µm and 215.0±20.4 µm, respectively, both P<0.001). After 3 years of follow-up, visual field area was associated with both CRAE (r=0.584, P<0.01) and CRVE (r=0.500, P=0.008). A significant association was also observed between mean deviation and CRAE (r=0.298, P=0.047). In eyes with RP, a narrower vessel caliber at baseline was associated with a larger decline in visual acuity over the 3-year follow-up interval (CRAE: r=-0.344, P=0.021; CRVE: r=-0.314, P=0.035). CONCLUSION: Retinal vessel caliber is associated with some visual functions in patients with RP.

Prevalence and spatial distribution of cystoid spaces in retinitis pigmentosa: investigation with spectral domain optical coherence tomography.

PURPOSE: To investigate the prevalence and spatial distribution of cystoid spaces (CS) in retinitis pigmentosa patients with spectral domain optical coherence tomography. METHODS: A total of 529 eyes of 275 patients with retinitis pigmentosa were examined with spectral domain optical coherence tomography. The presence or absence of CS was judged for each eye. Retinal layer and outer retinal status where the CS existed were also investigated. Statistical analysis was performed using 1 eye per 1 patient. RESULTS: Cystoid spaces were present in 119 of 529 eyes (22.5%) of 74 of 275 patients (26.9%). There were no significant differences between the cases with and without CS except for central foveal thickness (P < 0.001). Cystoid spaces were noted in the inner nuclear layer in almost all eyes (98.6%), and outer nuclear layer/outer plexiform layer was also involved in many eyes (27.8%). Cystoid spaces were sometimes seen in ganglion cell layer (6.9%). Cystoid spaces were predominantly (78.9%) distributed in the relatively preserved retina where external limiting membrane was retained. The presence of epiretinal membrane or posterior vitreous adhesion was associated with the presence of CS (P < 0.001) but showed no relationship with the spatial location of CS (P = 1.000). CONCLUSION: The prevalence of CS in patients with retinitis pigmentosa was 26.9% and contrary to previous reports, most CS were present in inner nuclear layer. In addition, most CS were observed in relatively retained retina, which is compatible to the prevailing notion. Epiretinal membrane or posterior vitreous adhesion was also associated with the development of CS. The distribution of CS in inner and preserved retina may provide insight for the pathogenesis of CS in retinitis pigmentosa.

Measurement of retinal nerve fiber layer thickness in eyes with optic disc swelling by using scanning laser polarimetry and optical coherence tomography.

BACKGROUND: The retinal nerve fiber layer thickness (RNFLT) in patients with optic disc swelling of different etiologies was compared using scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (OCT). METHODS: Forty-seven patients with optic disc swelling participated in the cross-sectional study. Both GDx SLP (enhanced corneal compensation) and Spectralis spectral-domain OCT measurements of RNFLT were made in 19 eyes with papilledema (PE), ten eyes with optic neuritis (ON), and 18 eyes with nonarteritic anterior ischemic optic neuropathy (NAION) at the neuro-ophthalmology clinic at Kyoto University Hospital. Differences in SLP (SLP-RNFLT) and OCT (OCT-RNFLT) measurements among different etiologies were investigated. RESULTS: No statistical differences in average OCT-RNFLT among PE, ON, and NAION patients were noted. Average SLP-RNFLT in NAION patients was smaller than in PE (P<0.01) or ON (P=0.02) patients. When RNFLT in each retinal quadrant was compared, no difference among etiologies was noted on OCT, but on SLP, the superior quadrant was thinner in NAION than in PE (P<0.001) or ON (P=0.001) patients. Compared with age-adjusted normative data of SLP-RNFLT, average SLP-RNFLT in PE (P<0.01) and ON (P<0.01) patients was greater. Superior SLP-RNFLT in NAION patients was smaller (P=0.026). The ratio of average SLP-RNFLT to average OCT-RNFLT was smaller in NAION than in PE (P=0.001) patients. CONCLUSION: In the setting of RNFL thickening, despite increased light retardance in PE and ON eyes, SLP revealed that NAION eyes have less retardance, possibly associated with ischemic axonal loss.

Macular cone abnormalities in retinitis pigmentosa with preserved central vision using adaptive optics scanning laser ophthalmoscopy.

PURPOSE: To assess macular photoreceptor abnormalities in eyes with retinitis pigmentosa (RP) with preserved central vision using adaptive optics scanning laser ophthalmoscopy (AO-SLO). METHODS: Fourteen eyes of 14 patients with RP (best-corrected visual acuity 20/20 or better) and 12 eyes of 12 volunteers underwent a full ophthalmologic examination, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), and imaging with a prototype AO-SLO system. Cone density and spatial organization of the cone mosaic were assessed using AO-SLO images. RESULTS: In 3 eyes with RP and preserved central vision, cones formed a mostly regular mosaic pattern with small patchy dark areas, and in 10 eyes, the cone mosaic patterns were less regular, and large dark regions with missing cones were apparent. Only one eye with RP demonstrated a normal, regular cone mosaic pattern. In eyes with RP, cone density was significantly lower at 0.5 mm and 1.0 mm from the center of the fovea compared to normal eyes (P<0.001 and 0.021, respectively). At 0.5 mm and 1.0 mm from the center of the fovea, a decreased number of cones had 6 neighbors in eyes with RP (P = 0.002 for both). Greater decrease in cone density was related to disruption of the photoreceptor inner segment (IS) ellipsoid band on SD-OCT images (P = 0.044); however, dark regions were seen on AO-SLO even in areas of continuous IS ellipsoid on SD-OCT. Decreased cone density correlated thinner outer nuclear layer (P = 0.029) and thinner inner segment and outer segment thickness (P = 0.011) on SD-OCT. CONCLUSIONS: Cone density is decreased and the regularity of the cone mosaic spatial arrangement is disrupted in eyes with RP, even when visual acuity and foveal sensitivity are good. AO-SLO imaging is a sensitive quantitative tool for detecting photoreceptor abnormalities in eyes with RP.

Clinical and immunological characterization of paraneoplastic retinopathy.

PURPOSE: To report the clinical and immunological characterization of paraneoplastic retinopathy (PR) and to investigate the association between spectral-domain optical coherence tomography (SDOCT) findings and the targets of autoantibodies in PR. METHODS: We retrospectively enrolled eight patients (age range, 57-85 years; four men and four women) suspected of having PR. All patients underwent comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp examinations, kinetic visual field testing with Goldmann perimetry, electroretinography (ERG), fundus photography, fluorescein angiography, fundus autofluorescence (FAF), SDOCT, and serum sample tests (Western blot analysis and immunohistochemistry [IHC]). RESULTS: Three patients had a history of malignant tumors, and four patients were newly diagnosed as having neoplastic tumors (small cell lung carcinoma [SCLC], thymoma, pancreatic neuroendocrine neoplasm, and colon cancer). Another de novo malignancy (SCLC) was detected in a patient with a history of malignancy (bladder cancer and liposarcoma). The BCVA in these patients ranged from hand motion to 1.5. Goldmann perimetry revealed island, ring-shaped, concentric, or central scotoma. All patients showed nonrecordable or reduced amplitude results on ERG. Fluorescein leakage was detected in five patients. Hyperautofluorescence and/or hypoautofluorescence on FAF was detected in six patients. The serum sample tests identified anti-retinal antibodies in all patients. Patients whose serum contained anti-photoreceptor or anti-retinal pigment epithelium antibody on IHC showed damage of the outer retina on SDOCT. CONCLUSIONS: In this case series, PR was associated with a variety of neoplasms and autoantibodies. Spectral-domain OCT can be used to characterize morphologic changes, and the changes were associated with the targets of autoantibodies.

Wide-field fundus autofluorescence imaging of retinitis pigmentosa.

PURPOSE: To evaluate the clinical usefulness of wide-field fundus autofluorescence (FAF) imaging in patients with retinitis pigmentosa (RP). DESIGN: Cross-sectional case series. PARTICIPANTS: Seventy-five eyes of 75 patients with RP. METHODS: We examined the eyes of the RP patients using the Optos 200Tx imaging system (Optos PLC, Dunfermline, United Kingdom) and identified abnormal FAF patterns such as ring hyperautofluorescence and patchy hypoautofluorescent areas. Patients with hyperautofluorescent rings or foveal hyperautofluorescence were compared with those without such findings. We determined the percentage area occupied by the FAF abnormalities within a defined region of the eye and examined the relationship between the percentage area of these abnormalities and the visual field area. Moreover, we categorized the patients into 3 different groups based on the presence of a patchy hypoautofluorescent lesion larger than 1 disc diameter: Group A consisted of those with patchy lesions smaller than 1 disc diameter, group B consisted of those with patchy lesions larger than 1 disc diameter but present in only 1 quadrant, and group C consisted of those with patchy lesions larger than 1 disc diameter and present in more than 1 quadrant. In addition, various clinical characteristics were compared among these 3 groups. MAIN OUTCOME MEASURES: Predicting the visual field size and duration of the disease in RP patients based on FAF patterns. RESULTS: Patients without hyperautofluorescent rings or foveal hyperautofluorescence had better visual acuity or mean deviation measured with a Humphrey perimeter. The total area of the abnormal FAF image correlated with the visual field area measured with a Goldmann perimeter (R = -0.64, P<0.001). The individuals with the large patchy hypofluorescent areas (i.e., larger than 1 disc diameter) were older than those with small patchy hypofluorescent areas (group A vs. groups B and C, P = 0.002 and P<0.001, respectively) and had experienced the symptoms for longer durations (group A vs. groups B and C, P<0.05 and P<0.001, respectively). CONCLUSIONS: We can estimate the visual field in patients with RP using the objective measurements from wide-field FAF. The presence of patchy hypofluorescent lesions can be used an indicator of the duration of RP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

[Genotype screening of retinal dystrophies in the Japanese population using a microarray].

PURPOSE: To investigate the pathogenic variants of retinal dystrophies in the Japanese population using microarray analysis. SUBJECTS AND METHODS: DNA extracted from the blood samples of 84 families (87 patients) with retinal dystrophies (retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy and Bietti's crystalline retinopathy) was screened by Asper Biotech services. All the variants detected by microarray analysis were verified by direct sequencing. RESULTS: Mutations were detected in 2 of 36 families with autosomal dominant retinitis pigmentosa, 2 of 4 with Leber congenital amaurosis, 11 of 24 with cone-rod dystrophy, 3 of 7 with macular dystrophy and 6 of 7 with Bietti's crystalline retinopathy. CONCLUSION: Genotype screening using microarray analysis can be effectively used to determine the variants of retinal dystrophies, except retinitis pigmentosa, in the Japanese population.

The time course changes of choroidal neovascularization in angioid streaks.

PURPOSE: To assess the clinical course of choroidal neovascularization (CNV) in patients with angioid streaks using optical coherence tomography and fluorescein angiography/indocyanine green angiography. METHODS: We examined a consecutive series of 88 eyes of 44 patients with angioid streaks using color fundus photography, optical coherence tomography, and fluorescein angiography/indocyanine green angiography. RESULTS: At the initial visit, 33 eyes exhibited no CNV, 2 exhibited polypoidal choroidal vasculopathy, 8 exhibited Type 1 CNV, 32 exhibited active Type 2 CNV, and 13 exhibited a fibrotic scar. In addition to the 2 eyes that exhibited macular polypoidal choroidal vasculopathy at the initial visit, 3 exhibited peripapillary polypoidal lesions, and 2 exhibited polypoidal lesions at the edge of the preexisting Type 2 CNV/fibrosis. During the follow-up, Type 2 CNV developed in 4 eyes on the basis of Type 1 CNV. Visual acuity was worse in eyes with Type 2 CNV and fibrosis than in those with Type 1 CNV, while polypoidal choroidal vasculopathy did not affect the visual acuity. CONCLUSION: Eyes with angioid streaks can develop any form of CNV including polypoidal choroidal vasculopathy. Considering the worse visual acuity in eyes with Type 2 CNV and fibrosis, patients should be carefully observed so as to treat them promptly when Type 2 CNV occurred beneath the fovea.

Horizontal deviation as diagnostic and prognostic values in isolated fourth nerve palsy.

BACKGROUND/AIMS: To investigate the causes of isolated fourth nerve palsy (IFNP) and the association among aetiology, prognosis and ocular deviation. METHODS: A total of 126 consecutive cases of IFNP was retrospectively reviewed. According to aetiologies, all patients were classified into five groups: microvascular, congenital, decompensation of congenital, traumatic and others. We investigated the recovery rate of IFNP patients who could be followed for more than 6 months or until they recovered completely. Patients also had the magnitude of vertical and horizontal ocular deviations (prism diopter) measured in the primary eye position on the first visit. RESULTS: Major causes of IFNP were microvascular (47%) and decompensated (33%). The rate of recovery was significantly different between microvascular IFNP and decompensated IFNP (92% vs 55%, p<0.001). There were no differences in both age of onset or mean vertical deviation between the two aetiologies (68.6±9.8 vs 65.4±13.3, 5.7±3.3 vs 7.8±7.9). However, for mean horizontal deviation, there was a significant difference between microvascular and decompensated IFNP (0.4±3.0 vs 4.9±5.6, p<0.001). Although the fourth nerve abducts the eyeball, 69 of 126 cases (55%) showed exotropia. The microvascular IFNP group included more cases of exodeviation, while the decompensated IFNP group included more cases of esodeviation (p<0.001). CONCLUSIONS: Contrary to previous thinking, the horizontal deviation of IFNP mainly showed exodeviation, and the degree of horizontal deviation is useful for making a determination between vasculopathic and decompensated IFNP. This differentiation could be critical for predicting the outcome.

Knockout of ccr2 alleviates photoreceptor cell death in a model of retinitis pigmentosa.

Neuroinflammation involving CC chemokines such as monocyte chemoattractant protein-1 (MCP-1) has been demonstrated in the pathological process of retinitis pigmentosa (RP), an inherited degenerative retinal disease. However, the mechanism of MCP-1 and its receptor CCR2 involvement in the disease remains unclear. To investigate the role of MCP1/CCR2 in RP pathogenesis, ccr2 mutant RP mice (ccr2(-/-) rd10) were created and analyzed. The expression of MCP-1, RANTES, stromal cell-derived factor (SDF-1), and tumor necrosis factor-α (TNF-α) in the retinas of wild-type, rd10, and ccr2(-/-) rd10 mice was analyzed using quantitative RT-PCR. Photoreceptor apoptosis (TUNEL staining) and the number of microglia (positive for the F4/80 antibody) in the retina were examined. Retinal function was assessed using electroretinograms, and the structure of the whole retina was analyzed from images obtained using optical coherence tomography (OCT) and by histological examination. The expression levels of MCP-1, RANTES, and SDF-1 increased with time in the rd10 mice but not in the wild-type mice. Rearing the mice in the dark prevented degeneration and resulted in thicker photoreceptor layers at each time point. In those mice, the peaks of chemokine expression shifted to a later time with degeneration, suggesting that the expression of these chemokines was induced during the progression of degeneration. Although the difference was not so obvious, the retina in the ccr2(-/-) rd10 mice was consistently and significantly thicker than that in the rd10 (ccr2(+/+) rd10) mice at all time points. Rhodopsin gene expression was also higher in the ccr2(-/-) rd10 mice than in rd10 (ccr2(+/+) rd10) mice, suggesting photoreceptor survival in the former. Retinal function was also better preserved in the ccr2(-/-) rd10 mice than in the rd10 mice. The number of microglia in the retinas of the ccr2(-/-) rd10 mice was significantly lower than that in the retinas of the rd10 mice. Interestingly, the MCP-1 induction that was observed in the retinas of the rd10 mice was diminished in the retinas of the ccr2(-/-) rd10 mice. Our results suggest that the MCP-1/CCR2 system plays a role in retinal degeneration in rd mouse retinas. Retinal MCP-1 expression in the rd mouse retina may be partially controlled by ccr2-positive circulating cells.

Outer retinal circular structures in patients with Bietti crystalline retinopathy.

BACKGROUND: Bietti crystalline retinopathy (BCR) is a distinct retinal degenerative disease characterised by retinal degeneration with many yellow-white crystals located mainly at the posterior pole area. Using spectral domain-optical coherence tomography (SD-OCT), the structural change in retina was investigated. METHODS: Patients diagnosed with BCR (n=12), retinitis pigmentosa (RP, n=292) and cone dystrophy (n=16) were included in this study. The authors mainly examined fundus photographs and SD-OCT, infrared and fundus autofluorescence images of these patients. RESULTS: Crystalline deposits were detected in portions of the retinal pigment epithelium that lacked patchy degenerated lesions. SD-OCT revealed that most of the observed crystalline deposits were located adjacent to the inner side of retinal pigment epithelium layer. The change most frequently observed was circular hyper-refractive structures in the outer nuclear layer. Although the structures were considered to be previously reported "tubular formation" or "tubular degeneration", we determined that many of these circular structures were slices of spherical structures and were typically noted in areas suspected of ongoing active degeneration. CONCLUSION: BCR has characteristic structures in the outer nuclear layer. Although the incidence of the structure varies, it may be characteristic of retinal degeneration and can be found in many retinal degenerative diseases.

Granulocyte colony-stimulating factor attenuates oxidative stress-induced apoptosis in vascular endothelial cells and exhibits functional and morphologic protective effect in oxygen-induced retinopathy.

Granulocyte colony-stimulating factor (G-CSF) is a known hematopoietic glycoprotein, and recent studies have revealed that G-CSF possesses other interesting properties. Oxidative stress is involved in many diseases, such as atherosclerosis, heart failure, myocardial infarction, Alzheimer disease, and diabetic retinopathy. This study was designed to examine whether G-CSF has a protective effect on endothelial cells against oxidative stress and to investigate whether G-CSF has a therapeutic role in ischemic vascular diseases. Expression of G-CSF (P < .01) and G-CSF receptor (P < .05) mRNA in human retinal endothelial cells (HRECs) was significantly up-regulated by oxidative stress. Treatment with 100 ng/mL G-CSF significantly reduced H(2)O(2)-induced apoptosis in HRECs from 61.7% to 41.4% (P < .05). Akt was phosphorylated in HRECs by G-CSF addition, and LY294002, a PI3K inhibitor, significantly attenuated the antiapoptotic effect of G-CSF (by 44.1%, P < .05). The rescue effect was also observed in human umbilical vein endothelial cells. In mouse oxygen-induced retinopathy model, G-CSF significantly reduced vascular obliteration (P < .01) and neovascular tuft formation (P < .01). G-CSF treatment also clearly rescued the functional and morphologic deterioration of the neural retina. A possibility of a novel therapeutic strategy for ischemic diseases through attenuating vascular regression using G-CSF was proposed.

Punctate hyperfluorescent spots associated with central serous chorioretinopathy as seen on indocyanine green angiography.

PURPOSE: The purpose of this study was to examine indocyanine green angiography of eyes with central serous chorioretinopathy (CSC). METHODS: We retrospectively studied the medical records of 39 patients (41 eyes) with active CSC who were <50 years of age. All patients had undergone fluorescein angiography and indocyanine green angiography using a confocal laser scanning system. RESULTS: On indocyanine green angiography, most patients showed choroidal abnormalities, such as filling delay, venous dilation, subretinal leakage, or focal areas of hyperfluorescence, that were attributed to choroidal vascular hyperpermeability. In addition, punctate hyperfluorescent spots were seen in 38 of 41 eyes (93%) with active CSC and in 29 of 37 fellow eyes (78%); these spots were seen in the macular area and outside the vascular arcade or in peripapillary locations, and they often appeared as clusters of distinct spots. A cluster of punctate hyperfluorescent spots was seen on midphase indocyanine green angiography, and focal areas of hyperfluorescence often appeared to expand with time from these punctate hyperfluorescent spots. CONCLUSION: Focal areas of hyperpermeability in CSC may be derived from the leakage of tiny punctate spots in the inner choroid. Hyperpermeability of these lesions may be involved in the development of serous retinal detachment associated with CSC.

Three-dimensional CT and histopathological findings of airway malacia in Hunter syndrome.

A 19-year-old man with known Hunter syndrome presented with dyspnea, and was admitted to our hospital. Bronchoscopy revealed tracheal narrowing with excessive granulation tissue formation in the trachea. Three-dimensional CT clearly demonstrated severe stenosis in the trachea and both main bronchi. Autopsy showed granulomatous tissue proliferation and deposition of mucopolysaccharide in the tracheal wall. We demonstrated the clinico-radiological-pathological correlation of bronchial lesions in Hunter syndrome, and emphasized that three-dimensional CT is helpful in deciding upon therapeutic strategy to treat stenosis in the large airway.

Local and systemic expression of inducible nitric oxide synthase in comparison with that of cyclooxygenase-2 in rat carrageenin-induced pleurisy.

Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) is up-regulated in response to inflammatory stimuli. To evaluate the extent to which local pleural inflammation involves additional site in the pleural cavity and elsewhere, we investigated the time course of the levels of iNOS and its product in the inflammatory and other sites, and compared those with a level of COX-2 in rat carrageenin-induced pleurisy. The exudate and plasma NOx levels rose, reaching peaks at 9 and 14 h, respectively. Both COX-2 and iNOS became detectable in exudate leukocytes, their levels reaching peaks at 3 and 9 h after irritation, respectively. COX-2 was detectable mainly in neutrophils, but iNOS was detectable in both neutrophils and mononuclear leukocytes. Furthermore, iNOS became detectable in neutrophils and mononuclear leukocytes in enlarged parathymic lymph nodes from 3h in addition to those in peripheral blood and Kupffer cells from 3 to 14 h, respectively. The gene product is also detectable in thymic large dendritic cells of pleurisy-induced rats as well as normal control rats. COX-2 became detectable in stellar dendritic cells of the enlarged draining lymph nodes from 14 h. Thus, these gene products were induced in the immediate proximity of regional lymph nodes, and even at a considerable distance of liver by the local inflammatory stimulus. Although their expression pattern was quite different from each other, these gene products were detectable in phagocytic cells.