Inhibition of Connective Tissue Growth Factor Expression in Adult Retinal Pigment Epithelial-19 Cells by Blocking Yes-Associated Protein/Transcriptional Coactivator with PDZ-Binding Motif Activity.

Purpose: To investigate the effect of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) on connective tissue growth factor (CTGF) expression in adult retinal pigment epithelial (ARPE)-19 cells. We also studied the inhibitory effect of K-975, a new pan-transcriptional enhanced associate domain (TEAD) inhibitor, and luteolin, a plant-derived flavonoid on CTGF expression. Methods: ARPE-19 cells were transfected with either YAP or TAZ overexpression plasmid or treated with transforming growth factor (TGF)-ß2. The cells were cultured either with or without K-975 or luteolin. The expression of YAP, TAZ, and CTGF was examined using real-time PCR. Results: ARPE-19 cells overexpressing YAP or TAZ exhibited significantly increased CTGF expression. This increase was attenuated by K-975 or luteolin alone. TGF-ß2 treatment significantly raised the expression of not just YAP and TAZ, but also CTGF in ARPE-19 cells. TGF-ß2 treatment-enhanced CTGF expression was considerably lowered by the addition of K-975 or luteolin. Conclusions: Overexpression of YAP or TAZ and treatment with TGF-ß2 led to an increase in the expression of CTGF in ARPE-19 cells. These increases were attenuated by treatment with K-975 and luteolin. These findings suggest that YAP and TAZ may be related to the expression of CTGF in ARPE-19 cells and that K-975 and luteolin can be explored as potential therapeutic agents for preventing CTGF production in vitreoretinal fibrosis.

Ten-year outcomes of congenital cataract surgery performed within the first 6 months of life.

PURPOSE: In the spectrum of pediatric cataract, genuine congenital cataract poses challenges and has a poorer prognosis than developmental cataract. We investigated the long-term outcomes of congenital cataract surgery performed within the first 6 months of life. SETTING: Eleven ophthalmic surgical sites in Japan. METHODS: Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia. RESULTS: Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this timeframe. The incidence of secondary glaucoma was similar between groups, while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes. CONCLUSIONS: In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of intraocular lens with sophisticated surgical techniques shows promise even in congenital cataract surgery.

Long-term surgical outcomes of pediatric cataract-multivariate analysis of prognostic factors.

We assessed the 10-year postoperative outcomes of pediatric cataract patients who underwent surgery at the age of 6 years or younger. A retrospective review of medical charts was conducted for 457 eyes of 277 patients, with the age at surgery averaging 1.3 ± 1.5 years (mean ± SD) and the follow-up duration averaging 12.8 ± 2.4 years (ranging from 10 to 17 years). The cohort included 250 eyes of 125 cases with bilateral aphakia (age at surgery 0.5 ± 0.8 years), 110 eyes of 55 cases with bilateral pseudophakia (1.9 ± 1.6 years), 42 cases with unilateral aphakia (1.1 ± 1.3 years), and 55 cases with unilateral pseudophakia (2.6 ± 1.7). A forward stepwise multiple regression analysis revealed that the best-corrected visual acuity at the final visit was significantly associated with laterality of cataract (with bilateral cases showing better results compared to unilateral cases), presence of systemic comorbidities, presence of ocular comorbidities, development of glaucoma, and phakic status (with better results in the pseudophakia group than the aphakia group). The age at surgery did not significantly affect visual acuity outcomes. A multiple logistic regression analysis demonstrated that the incidence of secondary glaucoma was significantly linked to younger age at surgery, phakic status (higher in aphakic than pseudophakic eyes), and presence of systemic comorbidities. In conclusion, after pediatric cataract surgery, final visual acuity was better in patients with bilateral cataracts, those treated with an intraocular lens, and cases without systemic or ocular comorbidities and secondary glaucoma. The development of secondary glaucoma was linked to younger age at surgery, aphakic status, and presence of systemic comorbidities.

Time Course of Lens Epithelial Cell Behavior in Rabbit Eyes following Lens Extraction and Implantation of Intraocular Lens.

BACKGROUND: After cataract surgery, some lens epithelial cells (LECs) transdifferentiate into myofibroblast-like cells, which causes fibric posterior capsule opacification (PCO). Residual LECs differentiate into lens fiber cells, forming Elschnig pearls with PCO. This study was carried out to identify the time course of both types of LEC behavior in rabbit eyes following lens extraction and implantation of an intraocular lens (IOL). METHODS: Phacoemulsification and implantation of posterior chamber IOLs were performed in rabbit eyes. Following enucleation, immunohistochemical methods were used to detect α-smooth muscle actin (α-SMA), a marker for myofibroblast-like cells, in the pseudophakic rabbit eyes. A mouse monoclonal antibody against α-SMA was used. RESULTS: Soon after the operation, the LECs migrated and covered the lens capsule. Thereafter, the LECs around the anterior capsular margin were always positive for α-SMA. However, the distributions of these cells were not consistent. In some specimens, α-SMA-positive LECs were present around the IOL optic early after surgery, but most of them had disappeared several weeks after the surgery. The residual cells induced fibrotic PCO. In the other specimens, most LECs around the IOL optic except the anterior capsular margin were negative for α-SMA. In the peripheral region covered by the peripheral anterior and posterior capsules, LECs on the posterior capsule always differentiated into lens fiber cells and formed a Soemmering ring. Thereafter, migration of lens fiber cells from the Soemmering ring and differentiation of LECs in situ on the central posterior capsule consisted of Elschnig pearls type of PCO. CONCLUSIONS: Although postoperative LEC behavior is not consistent, residual α-SMA-positive LECs induced fibrotic PCO. The lens fiber cells that migrated from the peripheral capsular bag or that were differentiated in situ covered the central posterior capsule, forming Elschnig pearls with PCO.

Blue light-filtering and violet light-filtering hydrophobic acrylic foldable intraocular lenses: Intraindividual comparison.

PURPOSE: To compare the clinical outcomes after cataract surgery and implantation of a blue light-filtering IOL (AcrySof IQ SN60WF) or a violet light-filtering intraocular lens (IOL) (OptiBlue ZCB00V). SETTING: Four surgical sites in Japan. DESIGN: Prospective case series. METHODS: One eye of patients with bilateral cataract was randomly allocated to the blue light-filtering IOL and the fellow eye to the violet light-filtering IOL. Visual acuity and contrast sensitivity were assessed over 3 months. The incidence of cyanopsia was evaluated using the neutralization method. RESULTS: The study enrolled 110 eyes of 55 patients. There was no significant difference in visual acuity between the two IOLs. Based on the neutralization results 1 week postoperatively, 15 cases (27.8%) with the light-filtering IOL and 8 cases (14.8%) with the violent light-filtering IOL had cyanopsia; the difference reached statistical significance (P = .049). After 2 weeks, the difference in the incidence of cyanopsia was not significant. Postoperative contrast sensitivity under photopic condition at 1 week and 3 months and contrast sensitivity under mesopic conditions at 3 months were significantly better with the violet light-filtering IOL than with the blue light-filtering IOL (P < .05). CONCLUSIONS: The violet light-filtering IOL yielded highly satisfactory clinical outcomes, including reduction of cyanopsia and a potential improvement in contrast sensitivity. The different chromophores of the IOL and its different material and design might have contributed.

Topical administration of a ROCK inhibitor prevents anterior subcapsular cataract induced by UV-B irradiation.

The deposition of extracellular matrix (ECM)-which is mainly composed of type I collagen-in anterior subcapsular cataracts (ASCs) during epithelial-to-mesenchymal transition (EMT) of lens epithelial cells (LECs) decreases visual function. Transforming growth factor (TGF)-ß is a key factor in the induction of EMT in LECs. Although Rho kinase (ROCK) plays an important role in EMT induced by TGF-ß, it is unknown whether ROCK inhibition affects type I collagen expression in TGF-ß-stimulated LECs and ASC formation. This was investigated in the present study both in vitro using human lens epithelium (HLE)-B3 cells and in vivo using mice with ultraviolet radiation (UVR)-B-induced cataracts. We found that TGF-ß2 increased type I collagen mRNA expression in HLE-B3 cells; this was inhibited in a dose-dependent manner by treatment with the ROCK inhibitor Y-27632. UVR-B exposure caused ASC formation in mice. A histopathological examination revealed that LECs in the anterior subcapsular area were flattened and multi-layered, and had a spindle shape in cross section. Immunohistochemical analysis revealed the presence of α-smooth muscle actin and type I collagen around these flattened LECs; these opacities were reduced by topical instillation of Y-27632. These findings suggest that suppression of TGF-ß signaling in LECs by topical application of a ROCK inhibitor can prevent the formation of ASCs.

Live imaging of primary ocular vasculature formation in zebrafish.

Ocular vasculature consists of the central retinal and ciliary vascular systems, which are essential to maintaining visual function. Many researchers have attempted to determine their origins and development; however, the detailed, stepwise process of ocular vasculature formation has not been established. In zebrafish, two angioblast clusters, the rostral and midbrain organizing centers, form almost all of the cranial vasculature, including the ocular vasculature, and these are from where the cerebral arterial and venous angioblast clusters, respectively, differentiate. In this study, we first determined the anatomical architecture of the primary ocular vasculature and then followed its path from the two cerebral angioblast clusters using a time-lapse analysis of living Tg(flk1:EGFP)k7 zebrafish embryos, in which the endothelial cells specifically expressed enhanced green fluorescent protein. We succeeded in capturing images of the primary ocular vasculature formation and were able to determine the origin of each ocular vessel. In zebrafish, the hyaloid and ciliary arterial systems first organized independently, and then anastomosed via the inner optic circle on the surface of the lens by the lateral transfer of the optic vein. Finally, the choroidal vascular plexus formed around the eyeball to complete the primary ocular vasculature formation. To our knowledge, this study is the first to report successful capture of circular integration of the optic artery and vein, lateral transfer of the optic vein to integrate the hyaloidal and superficial ocular vasculatures, and formation of the choroidal vascular plexus. Furthermore, this new morphological information enables us to assess the entire process of the primary ocular vasculature formation, which will be useful for its precise understanding.

Comparisons of focal macular electroretinograms after indocyanine green-, brilliant blue G-, or triamcinolone acetonide-assisted macular hole surgery.

PURPOSE: To compare the effects of indocyanine green (ICG)-, brilliant blue G (BBG)-, or triamcinolone acetonide (TA)-assisted internal limiting membrane (ILM) peeling during macular hole (MH) surgery on the different components of the focal macular electroretinograms (fmERGs). METHODS: Forty-eight eyes of 48 patients with a macular hole were randomly divided into those undergoing ICG-, BBG-, or TA-assisted vitrectomy (n = 16 for each group). All patients had combined cataract and macular hole surgery with ILM peeling. The fmERGs were recorded before, and 1, 3, 6, 9, and 12 months postoperatively. The amplitudes and implicit times of the a- and b-waves, the amplitudes of the sum of the oscillatory potentials (ΣOPs), and the photopic negative responses (PhNRs) were analyzed. RESULTS: The amplitudes of all of the components of the fmERGs gradually increased with time after surgery (P < 0.005). The implicit times of the a- and b-waves were significantly prolonged at 1 month (P < 0.01) and then gradually returned to the baseline times. No significant differences were found in these changes among the groups. In pooled data from the 48 patients, the PhNR amplitude increased more than the a- and b-waves and the ΣOPs amplitudes at every time point after 3 months (P < 0.005). CONCLUSIONS: The lack of significant differences on the different components of the fmERGs indicates that none of the three agents was toxic to the macula. After closure of a MH, the function of the retinal ganglion cells may recover more than that of the other neural elements in the macular area.

Effect of Geranylgeranylacetone on Ultraviolet Radiation Type B-Induced Cataract in Heat-Shock Transcription Factor 1 Heterozygous Mouse.

PURPOSE: We investigated whether heat-shock transcription factor 1 (HSF1) was involved in ultraviolet radiation type B (UVR-B)-induced lens opacity (cataract) using HSF1 heterozygous mice. We also examined the effects of geranylgeranylacetone (GGA), an inducer of heat-shock proteins via activation of HSF, on the UVR-B-induced cataract. MATERIAL AND METHODS: Male HSF1+/- and WT mice were unilaterally exposed to UVR-B (total: 1200mJ) at 16 weeks of age. At 48 h after the last UVR-B irradiation, the lens was isolated and the induction of the cataract was quantified as the cataract area ratio (opacity area/anterior capsule). GGA was orally administered at a dosage of 500 mg/kg once a day for two days before the first UVR-B exposure until the end of the experiment (21days in total). RESULTS: The HSF1 expression was more greatly decreased in the lens from HSF1+/- mice than in that from WT mice (p < 0.01). UVR-B exposure could mainly induce cataracts in the anterior capsule in both HSF1+/- and WT mice, while the opacity of the lens was markedly enhanced in HSF1+/- mice compared to that in WT mice(p (0.01). GGA treatment could prevent the induction of lens opacity by UVR-B exposure in both WT and HSF1+/- mice as compared with the non-administration group (p < 0.01). No obvious alteration by the UVR-B radiation was seen in lens protein levels of αA-crystallin, αB-crystallin, or γ-crystallin with or without GGA administration among all groups of mice. In contrast to the crystallins, the lens protein level of HSP25 was decreased by UVR-B exposure in both HSF1+/- and WT mice, and was significantly recovered in WT mice by the GGA treatment (p < 0.01). The induction of HSP25 was suppressed in HSF1+/- mice compared with that in WT mice. CONCLUSIONS: These data suggest that HSF1 plays an important role in the occurrence of UVR-B-induced cataracts, possibly via regulation of HSPs such as HSP25.

Different effect of serotonin on intracellular calcium ion dynamics in the smooth muscle cells between rat posterior ciliary artery and vorticose vein.

5-hydroxytriptamine (5-HT: serotonin) is an important transmitter that causes vessel constriction, although few studies have examined the effect of 5-HT on venous smooth muscles. The intracellular Ca(2+) concentration ([Ca(2+)]i) plays an essential role in stimulus-response coupling in numerous tissue/cells including vascular smooth muscle cells. The present study was performed to examine whether differences between arteries and veins in the response to 5-HT can be detected under confocal microscope with respect to [Ca(2+)]i dynamics. In posterior ciliary arteries of rats, 5-HT induced a [Ca(2+)]i increase. The 5-HT-induced responses were caused by both Ca(2+) influx and mobilization. Agonist and antagonist experiments revealed that arterial smooth muscles possess 5-HT1a, 1b, 2 (Gprotein-coupled type) and 5-HT3 (ion channel type) receptors, and that 5-HT2 in particular plays a major role in these responses. For vorticose veins, the 5-HT-induced responses were also caused by both Ca(2+) influx and mobilization. However, the cAMP dependent pathway (5-HT4-7) was found to be significant in vasocontraction with respect to 5-HT in these vessels. Thus, Ca(2+) mobilization was induced by 5-HT2 and 5-HT4-7 in a vessel-dependent manner, whereas Ca(2+) influx universally was induced by 5-HT3. These results indicate that the posterior ciliary arteries and vorticose veins in the same tissue might differ greatly in their responses to stimulus.

Surgical outcomes of congenital and developmental cataracts in Japan.

PURPOSE: To retrospectively analyze the surgical outcomes of congenital/developmental cataracts in Japan. METHODS: A mail questionnaire was sent to facilities engaged in surgical treatment of congenital cataracts. RESULTS: Twenty-nine facilities reported on 809 eyes of 508 patients with congenital/developmental cataracts. Three hundred fifty-nine eyes underwent intraocular lens implantation (pseudophakia group), while 450 eyes were left aphakic (aphakia group). The average age at surgery was significantly higher in the pseudophakia group (70 ± 53 months) than in the aphakia group (14 ± 24 months) (P < 0.0001). A significantly larger proportion of patients with unilateral cataract (52.0 %) received IOL implantation than did those with bilateral cataracts (42.6 %) (P = 0.0224). The prevalence of associated ocular disorders, such as nystagmus, microcornea, nanophthalmos, and persistent fetal vasculature, was significantly higher in the aphakia group than in the pseudophakia group. Postoperatively, glaucoma developed more frequently in the aphakia group (5.8 %) than in the pseudophakia group (0.7 %) (P = 0.0003). Posterior capsule opacification developed more frequently in the pseudophakic eyes even when both posterior capsulotomy and anterior vitrectomy were performed, especially in patients aged 1 year or younger. Postoperative visual acuity was significantly better in the pseudophakia group than in the aphakia group, both in the unilateral and in the bilateral cases. CONCLUSIONS: Surgeons tended to select IOL implantation, rather than to leave the eye aphakic, in patients who were older at the time of surgery, had fewer coexisting ocular disorders, and suffered from unilateral cataract. Under such circumstances, pseudophakic eyes obtained significantly better postoperative visual acuity than did aphakic eyes.

RETINAL PIGMENT EPITHELIUM UNDULATIONS IN ACUTE STAGE OF VOGT-KOYANAGI-HARADA DISEASE: Biomarker for Functional Outcomes After High-Dose Steroid Therapy.

PURPOSE: To determine the clinical significance of retinal pigment epithelium (RPE) undulations in the acute stage of Vogt-Koyanagi-Harada disease. METHODS: Retinal pigment epithelium undulations were detected and classified into 3 grades: Grade 1, slight; Grade 2, moderate; and Grade 3, severe undulations, in the enhanced depth imaging optical coherence tomographic images. The relationship between the clinical characteristics and the presence of RPE undulations was investigated. RESULTS: Among the 61 eyes of 31 patients with Vogt-Koyanagi-Harada disease, 40 eyes had some degree of RPE undulations (Grade 1 = 12, Grade 2 = 15, and Grade 3 = 13). The patients with RPE undulations in both eyes were significantly older at the onset (P = 0.0002). The eyes with RPE undulations were more likely to develop posterior recurrences (P = 0.032) and have worse vision at 12 months (P = 0.043). Multiple regression analysis revealed that RPE undulations were an independent predictor of posterior recurrences (P = 0.009) and poor visual outcomes (P = 0.035). CONCLUSION: Retinal pigment epithelium undulations detected by enhanced depth imaging optical coherence tomographic are relatively frequent occurrences at the acute stage of Vogt-Koyanagi-Harada, and their presence is a predictor of posterior recurrences and poor visual outcomes after high-dose steroid therapy.

α1-Adrenoceptors relate Ca(2+) modulation and protein secretions in rat lacrimal gland.

Noradrenaline (NA) is a catecholamine with multiple roles including as a hormone and a neurotransmitter. Cellular secretory activities are enhanced by adrenergic stimuli as well as by cholinergic stimuli. The present study aimed to determine which adrenoceptors play a role in controlling intracellular calcium ion ([Ca(2+)]i) level in acinar cells of rat lacrimal glands. Expression of mRNA for adrenoceptor subtypes in the acinar cells was assessed using RT-PCR. All types except α2c, ß1, and ß3 were detected. NA induced a [Ca(2+)]i increase with a biphasic pattern in the acinar cells. Removal of extracellular Ca(2+) and use of Ca(2+)-channel blockers did not inhibit the NA-induced [Ca(2+)]i increases. In contrast, U73122 and suramin almost blocked these increases. The α1-adrenoceptor agonist phenylephrine induced a strong increase in [Ca(2+)]i. However, clonidine and isoproterenol failed to induce a [Ca(2+)]i increase. The peroxidase activity was quantified as a measure of mucin secretion. Ca(2+)-dependent exocytotic secretion of peroxidase was detected in rat lacrimal glands. The RT-PCR results showed that MUC1, MUC4, MUC5AC, MUC5B, and MUC16 were expressed in acinar cells. These findings indicated that NA activates α1-adrenoceptors, which were found to be the main receptors in Ca(2+)-related cell homeostasis and protein (including mucin) secretion in lacrimal glands.

A survey of the surgical treatment of congenital and developmental cataracts in Japan.

PURPOSE: To understand the current practice pattern for the surgical treatment of congenital/developmental cataracts in Japan. METHODS: A mail questionnaire was sent to facilities engaged in the surgical treatment of congenital cataracts in Japan. RESULTS: Thirty-four facilities reported their preferred methods for the surgical treatment of congenital cataracts, including data from 809 eyes of 508 patients who had undergone surgery. More than 85% of the respondents answered that they would consider surgery even if the visual prognosis was not promising because of possible form-deprivation amblyopia. The most commonly performed surgical maneuvers were scleral tunnel incision (88.4%), 3.0-mm or smaller incision (78.8%), manual anterior continuous curvilinear capsulorhexis (90.2% success rate), posterior capsulotomy (92.5% for patients aged ≤6 years), anterior vitrectomy by the limbal approach (85.9% for patients aged ≤6 years), and wound closure with sutures (93.2%). Posterior capsulotomy and vitrectomy were not usually performed in patients aged >6 years. Implantation of an intraocular lens (IOL) was mostly indicated in patients aged 2 years or older. Implantation of an acrylic foldable IOL (76.6%) into the capsular bag (89.7%) was the most common practice among the surgeons. CONCLUSIONS: Small incision surgery with implantation of an acrylic foldable IOL into the capsular bag combined with posterior capsulotomy was the preferred surgical treatment of choice for congenital/developmental cataracts.

Clinical characteristics of congenital and developmental cataract undergoing surgical treatment.

PURPOSE: To analyze the clinical characteristics of congenital/developmental cataract undergoing surgery. METHODS: A mail questionnaire was sent to 49 facilities engaged in surgical treatment of congenital cataracts, and data on preoperative clinical features were collected. RESULTS: Twenty nine facilities reported on 864 eyes of 521 patients with congenital/infantile cataract, ranging in age at initial visit from 0 to 18.8 years (2.6 ± 3.3 years, mean ± standard deviation). Among the patients, 65.8 % had bilateral cataracts and 34.2 % were unilaterally affected. Family history was found for 22.4 % of cases, of which 98.1 % were bilateral. Family history was positive for 33.1 % of bilateral and 1.3 % of unilateral cases. The most common main complaint was white pupil for 35.7 % of bilateral cases and 32.7 % for unilateral cases. Concomitant systemic abnormalities were more frequently associated with bilateral cases (31.6 %) than with unilateral cases (16.7 %). Associated ocular diseases, such as strabismus, persistent fetal vasculature, and posterior lenticonus, were more frequently seen among unilateral cases whereas nystagmus was more common among bilateral cases. CONCLUSIONS: Among congenital/developmental cataracts, the ratio of bilateral and unilateral cases was approximately 2:1. Almost all patients with a family history of congenital cataract were bilateral. Initial visits to a physician were rather late, 2.6 years from birth; this should be improved.

Effect of astaxanthin on cataract formation induced by glucocorticoids in the chick embryo.

PURPOSE: To examine whether astaxanthin (AST) prevent the cataract formation induced by glucocorticoid in chick embryo. MATERIALS AND METHODS: Hydrocortisone hemisuccinate sodium (HC) (0.5 µmol/egg) was administered directly into the air chamber in the egg shell of chick embryo day 15. The eggs were then kept in an incubator at same conditions and administered 100 µL of 50 (HC + AST50 group), 80 (HC + AST80 group), 100 (HC + AST100 group) mg/mL of AST solutions dissolved in dimethyl sulfoxide (DMSO) 3 h after administration of HC. In addition, non-HC treated group (treated with physiological saline without HC and 100 µL of DMSO), HC-alone group (treated with 0.5 µmol of HC and 100 µL of DMSO), and AST100 group (treated with physiological saline without HC and 100 µL of DMSO) were also incorporated. After 48 h of treatment, lenses were removed from embryo and classified into five stages according to developed opacity. The amounts of reduced glutathione in the lenses and the blood glucose levels were measured. RESULTS: The average scores of lens opacitiy were 2.63 ± 1.02 nmol/lens (HC-alone), 2.78 ± 0.97 nmol/lens (HC + AST50), 2.22 ± 1.20 nmol/lens (HC + AST80) and 1.84 ± 0.83 nmol/lens (HC + AST100; p < 0.05), respectively. Administration of AST decreased the lens opacity dose-dependently. The amounts of reduced glutathione in lenses were 11.6 ± 2.8 nmol/lens (HC-alone), 11.3 ± 2.7 nmol/lens (HC + AST50), 13.4 ± 2.4 nmol/lens (HC + AST80) and 13.7 ± 3.1 nmol/lens (HC + AST100; p < 0.05), respectively. Higher levels of AST prevented loss of reduced glutathione from the lens. CONCLUSION: These findings support that AST protects glucocorticoid-induced cataract in chick embryo.

Regional variations in correlation between photopic negative response of focal electoretinograms and ganglion cell complex in glaucoma.

PURPOSE: To determine regional variations in a structure-function relationship, we correlated the the photopic negative response (PhNR) of the focal electoretinogram (ERG) with the ganglion cell complex (GCC) thickness in different retinal regions in patients with open angle glaucoma (OAG). METHODS: Fifty-one eyes of 51 OAG patients (OAG group) and 17 eyes of 17 normal volunteers (control group) were studied. The OAG patients had different degrees of glaucoma ranging from early to advanced stages. The focal ERGs were elicited by a white, 15° hemispherical stimulus placed superior or inferior to the fovea. Focal ERGs were also elicited by a half annulus placed superior or inferior to the macular region. The diameter of the inner border of the annulus was 15° and that of the outer border was 30°. The average GCC thickness in areas corresponding to the location of the stimuli was measured in SD-OCT images. RESULTS: The PhNR amplitude and PhNR/b-wave amplitude ratio were significantly correlated with the GCC thickness in the superior and inferior hemispherical areas (p < 0.0001). These ERG parameters were weakly correlated with the GCC thickness in the superior and inferior semi-annular areas (p < 0.05). There were significant differences in the slopes of the regression lines plotting the GCC thickness and the PhNR amplitude or the PhNR/b-wave amplitude ratio between the spherical and semi-annular areas (superior: p < 0.01, inferior: p < 0.0005). CONCLUSIONS: The thinning of the GCC affects the RGC function measured by the PhNR more strongly in the central retinal area than in the surrounding retinal areas.

Alterations of photopic negative response of multifocal electroretinogram in patients with glaucoma.

PURPOSE: To determine the effect of glaucoma on the multifocal electroretinograms (ERGs) (mfERGs) elicited by low-frequency stimuli. METHODS: Forty-four patients with open-angle glaucoma and 15 normal subjects were studied. The stimulus frequency was 6.25 Hz, and the stimulus was a circle with a 6.8° radius that was centered on the fovea (center). MfERGs were also elicited by a quarter of an annulus placed around the macula (superior/temporal; inferior/temporal; superior/nasal; and inferior/nasal quadrants). The radius of the inner border of the annulus was 6.8° and that of the outer border was 20°. The actual sensitivity was determined by standard automated perimetry. The thickness of the ganglion cell complex (GCC) was measured by optical coherence tomography. RESULTS: The mfERGs consisted of a negative wave (N1) followed by a positive wave (P1), and followed by a slow negative wave (N2). There were no significant differences in the response densities of N1 and P1 between the normal control and glaucomatous eyes in any areas. The N2 response density was significantly reduced with the severity of glaucoma in the center. There was a significant reduction even at an early stage of glaucoma compared to control values. In the center, the N2 response density was significantly correlated with the GCC thickness and mean sensitivity. However, in other stimulus areas, there was no significant reduction of any components of the mfERGs. CONCLUSIONS: These results suggest that the N2 component of the slow-sequence mfERGs is affected by glaucoma in the central retinal area. Regional variations in the contribution of the retinal ganglion cell activity to the N2 should be considered when examining the mfERGs in glaucoma patients.

Structures affecting recovery of macular function in patients with age-related macular degeneration after intravitreal ranibizumab.

PURPOSE: To determine the retinal structures affecting the recovery of macular function in patients with exudative age-related macular degeneration (AMD) treated with intravitreal ranibizumab (IVR). METHOD: Thirty eyes of 30 patients with exudative AMD who were treated with IVR at monthly intervals for 3 months were studied. Focal macular electroretinograms (fmERGs) and spectral-domain optical coherence tomography (SD-OCT) were performed before and 3 months after beginning the IVR injections. The fmERGs were elicited by a 15° white stimulus spot centered on the fovea. The thickness of different retinal layers, presence of a serous retinal detachment (SRD), and presence of a pigment epithelial detachment (PED) at the fovea was determined in the SD-OCT images. Measurements were made of the inner, middle, and outer layers of the retina and also of the SRD and PED in the horizontal and vertical meridians at 1.2 mm from the fovea (parafoveal regions). The significance of the correlations between these structural parameters and the a-wave amplitude of the fmERG was determined. RESULTS: There was no significant correlation between the structural parameters of the fovea and the a-wave amplitude. In the parafoveal regions, the thickness of the outer retinal layer was significantly correlated with an increase of the a-wave amplitude (R = 0.56, P = 0.001). In addition, the SRD thickness was negatively and significantly correlated with the a-wave amplitude (R = -0.54, P = 0.002). The change in the parafoveal SRD thickness after IVRs was the only independent determinant of recovery of the a-wave amplitude after the treatments (P < 0.05). CONCLUSIONS: The macular function measured by the fmERGs was determined by the parafoveal outer layer and SRD thickness in patients with exudative AMD. Of these, changes in the SRD thickness by IVRs most strongly affected the recovery of macular function.

Comparisons of retinal nerve fiber layer thickness after indocyanine green, brilliant blue g, or triamcinolone acetonide-assisted macular hole surgery.

Purpose. To compare the postoperative changes of the retinal nerve fiber layer (RNFL) thickness in patients with macular holes (MHs) treated with vitrectomy with indocyanine green- (ICG-), brilliant blue G- (BBG-), or triamcinolone acetonide- (TA-)assisted internal limiting membrane (ILM) peeling. Methods. Sixty-one eyes of 61 consecutive patients with MHs were studied. Each eye was randomly selected to undergo either ICG- (n = 18), BBG- (n = 21), or TA-assisted (n = 22) ILM peeling. The circumferential retinal nerve fiber layer (RNFL) thickness was determined by spectral-domain optical coherence tomography (SD-OCT) before and 1, 3, 6, 9, and 12 months postoperatively. The mean overall and the sectoral thicknesses of the RNFL were obtained for each group. Results. A transient increase of the RNFL thickness was seen in the mean overall and sectoral thicknesses except for the nasal/inferior sector at 1 month after surgery for the three groups. Then, the thickness gradually decreased and returned to the baseline level in all sectors except for the nasal/inferior sector. The differences in the RNFL thickness among the groups were not significant for at least 12 months postoperatively. Conclusions. The degree of change of the RNFL thickness was not significantly related to the type of vital stain used during MH surgery.