Minbin Yu

Dichoptic training enables the adult amblyopic brain to learn

Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye. But it is now clear that the adult human visual cortex has a significant degree of plasticity, suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see.

The Role of Suppression in Amblyopia

PURPOSE This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. METHODS Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. RESULTS There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. CONCLUSIONS These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Effects of Pirfenidone on Proliferation, Migration, and Collagen Contraction of Human Tenon’s Fibroblasts In Vitro

PURPOSE To investigate the effect of pirfenidone, a novel antifibrotic agent, on proliferation, migration, and collagen contraction of human Tenons fibroblasts (HTFs). METHODS After treatment of HTFs with pirfenidone, cell proliferation was measured by MTT assay. Cell migration was investigated by scratch assay. Contractility was evaluated in fibroblast-populated collagen gels. Cell viability was determined by trypan blue exclusion assay. The expression of TGF-beta1, -beta2, and -beta3 was estimated with RT-PCR, Western blot, and immunofluorescence analyses. RESULTS Pirfenidone induced significant dose-dependent inhibition of HTF proliferation and migration and collagen contraction. After treatment with different concentrations of pirfenidone (0.15, 0.3, and 1 mg/mL) for 24 and 72 hours, cell viability was not different in the treatment and control groups. After 24 hours of treatment with pirfenidone, HTFs showed dose-dependent decreases in mRNA and protein levels of TGF-beta1, -beta2, and -beta3. CONCLUSIONS These findings indicate that pirfenidone inhibits proliferation, migration, and collagen contraction of HTFs at nontoxic concentrations. A decrease in autocrine TGF-beta signaling may have a role in the effects of pirfenidone.

The effectiveness of progressive addition lenses on the progression of myopia in Chinese children

Purpose:  To evaluate the effectiveness of progressive addition lenses (PALs), with a near addition of +1.50 D, on the progression of myopia in Chinese children.

Quantifying Sensory Eye Dominance in the Normal Visual System: A New Technique and Insights into Variation across Traditional Tests

PURPOSE Although eye dominance assessment is used to assist clinical decision-making, current understanding is limited by inconsistencies across the range of available tests. A new psychophysical test of sensory eye dominance has been developed that objectively measures the relative contribution of each eye to a fused suprathreshold binocular percept. METHODS Six standard tests and the newly developed test were used to measure motor and sensory dominance in a group of 44 binocularly normal individuals (mean age, 29.5 ± 9.10 years). The new test required observers to perform a motion coherence task under dichoptic viewing conditions, wherein a population of moving, luminance-defined signal (coherently moving) and noise (randomly moving) dots were presented separately to each eye. The observers judged the motion direction of the signal dots. Motion coherence thresholds were measured by varying the ratio of signal-to-noise dots, in a staircase procedure. RESULTS The new dichoptic motion coherence threshold test revealed a clear bimodal distribution of sensory eye dominance strength, wherein the majority of the participants (61%) showed weak dominance, but a significant minority (39%) showed strong dominance. Subsequent analysis revealed that the strong-dominance group showed greater consistency across the range of traditional eye dominance tests used. CONCLUSIONS This new quantitative dichoptic motion coherence threshold technique suggests that there are two separate sensory eye dominance strength distributions among observers with normal binocular vision: weak and strong eye dominance. This finding may provide a basis for clinical decision-making by indicating whether eye dominance is likely to be an important consideration in a particular patient.

Evaluation of Pirfenidone as a New Postoperative Antiscarring Agent in Experimental Glaucoma Surgery

PURPOSE To investigate whether topical administration of pirfenidone eye drops could be used to prevent postoperative scarring in a rabbit model of experimental glaucoma filtration surgery. METHODS In a randomized, controlled, masked-observer study, 40 rabbits underwent trabeculectomy in the right eyes and randomly received postoperative administration of 0.1% or 0.5% pirfenidone, perioperative mitomycin C (0.25 mg/mL), or no treatment. Bleb characteristics and functions were evaluated over a period of 4 weeks. The animals were killed on days 7, 14, and 28. Histopathology and immunohistochemistry were performed to determine the amount of scarring and fibrosis. Ocular toxicity was assessed by the Draize test, histopathology, and electron microscope. RESULTS The four treatment groups were similar with respect to intraocular pressure and anterior chamber depth. Pirfenidone 0.5% significantly prolonged bleb survival, and the blebs were larger and higher than those in the control group (P < 0.05); the 0.1% pirfenidone concentration was less effective. Furthermore, the histology and immunohistology results showed that the 0.5% pirfenidone and mitomycin C groups had less scarring at days 7 to 28 than did the controls. Toxicity assessments showed that pirfenidone did not damage the rabbit eyes. CONCLUSIONS Postoperative use of 0.5% pirfenidone eye drops was associated with improved trabeculectomy bleb survival in a rabbit model. Pirfenidone eye drops may be a safe and effective antiscarring agent in glaucoma filtration surgery.

The Prevalence of Glaucoma in Adult Rural Chinese Populations of the Bai Nationality in Dali: The Yunnan Minority Eye Study

PURPOSE We evaluated the prevalence of glaucoma in adults of the Bai Nationality populations in rural China. METHODS A population-based survey of Chinese Bai Nationality aged ≥50 years from randomly selected block groups in southwestern China was conducted. Eligible persons were invited to local examination sites for a complete ophthalmic examination. Glaucoma was diagnosed using the International Society of Geographical and Epidemiological Ophthalmology Classification scheme. RESULTS In the study, 2133 subjects (77.8% participation rate) were examined, with a crude prevalence of all glaucoma of 2.2% (95% confidence interval [CI] 1.6%-2.9%). Primary open angle glaucoma (POAG) was found in 1.0% of cases (95% CI 0.6%-1.6%) and primary angle-closure glaucoma (PACG) in 0.9% (95% CI 0.6%-1.4%). The prevalence of all glaucoma was significantly higher in older people and women. Mean intraocular pressure (IOP) was 16.17 ± 3.74 mm Hg (97.5th and 99.5th percentiles, 24 mm Hg and 30 mm Hg, respectively). The mean vertical cup-to-disc ratio (VCDR) was 0.43 ± 0.17 (97.5th and 99.5th percentiles 0.7 and 0.8, respectively). Unilateral blindness was found in 80% of PACG, compared to only 36.3% of POAG cases. CONCLUSIONS Prevalence of POAG is similar to PACG in the ethnic Bai population living in rural southwestern China. PACG has a worse visual impairment and prognosis compared to POAG.

Quantitative Measurement of Interocular Suppression in Anisometropic Amblyopia : A Case-Control Study

OBJECTIVE The aims of this study were to assess (1) the relationship between interocular suppression and visual function in patients with anisometropic amblyopia, (2) whether suppression can be simulated in matched controls using monocular defocus or neutral density filters, (3) the effects of spectacle or rigid gas-permeable contact lens correction on suppression in patients with anisometropic amblyopia, and (4) the relationship between interocular suppression and outcomes of occlusion therapy. DESIGN Case-control study (aims 1-3) and cohort study (aim 4). PARTICIPANTS Forty-five participants with anisometropic amblyopia and 45 matched controls (mean age, 8.8 years for both groups). METHODS Interocular suppression was assessed using Bagolini striated lenses, neutral density filters, and an objective psychophysical technique that measures the amount of contrast imbalance between the 2 eyes that is required to overcome suppression (dichoptic motion coherence thresholds). Visual acuity was assessed using a logarithm minimum angle of resolution tumbling E chart and stereopsis using the Randot preschool test. MAIN OUTCOME MEASURES Interocular suppression assessed using dichoptic motion coherence thresholds. RESULTS Patients exhibited significantly stronger suppression than controls, and stronger suppression was correlated significantly with poorer visual acuity in amblyopic eyes. Reducing monocular acuity in controls to match that of cases using neutral density filters (luminance reduction) resulted in levels of interocular suppression comparable with that in patients. This was not the case for monocular defocus (optical blur). Rigid gas-permeable contact lens correction resulted in less suppression than spectacle correction, and stronger suppression was associated with poorer outcomes after occlusion therapy. CONCLUSIONS Interocular suppression plays a key role in the visual deficits associated with anisometropic amblyopia and can be simulated in controls by inducing a luminance difference between the eyes. Accurate quantification of suppression using the dichoptic motion coherence threshold technique may provide useful information for the management and treatment of anisometropic amblyopia. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Inhibition of Pirfenidone on TGF-beta2 Induced Proliferation, Migration and Epithlial-Mesenchymal Transition of Human Lens Epithelial Cells Line SRA01/04

Background Posterior capsular opacification (PCO) is a common complication of cataract surgery. Transforming growth factor-β2 (TGF-β2) plays important roles in the development of PCO. The existing pharmacological treatments are not satisfactory and can have toxic side effects. Methodologies/Principal Findings We evaluated the effect of pirfenidone on proliferation, migration and epithlial-mesenchymal transition of human lens epithelial cell line SRA01/04 (HLECs) in vitro. After treatment with 0, 0.25, and 0.5 mg/ml pirfenidone, cell proliferation was measured by MTT assay. Cell viability was determined by trypan blue exclusion assay and measurement of lactate dehydrogenase (LDH) activity released from the damaged cells. And cell migration was measured by scratch assay in the absence or presence of transforming growth factor-β2 (TGF-β2). The expressions of TGF-β2 and SMADs were evaluated with real-time RT-PCR, western blot, and immunofluorescence analyses. The mesenchymal phenotypic marker fibronectin (FN) was demonstrated by Immunocytofluorescence analyses. The cells had high viability, which did not vary across different concentrations of pirfenidone (0 [control] 0.3, 0.5 or 1.0 mg/ml) after 24 hours. Pirfenidone (0∼0.5 mg/ml) had no significant cytotoxicity effect on SRA01/04 by LDH assay. Pirfenidone significantly inhibited the proliferation and TGF-β2-induced cell migration and the effects were dose-dependent, and inhibited TGF-β2-induced fibroblastic phenotypes and TGF-β2-induced expression of FN in SRA01/04 cells. The cells showed dose-dependent decreases in mRNA and protein levels of TGF-β2 and SMADs. Pirfenidone also depressed the TGF-β2-induced expression of SMADs and blocked the nuclear translocation of SMADs in cells. Conclusion Pirfenidone inhibits TGF-β2-induced proliferation, migration and epithlial-mesenchymal transition of human lens epithelial cells line SRA01/04 at nontoxic concentrations. This effect may be achieved by down regulation of TGF-β/SAMD signaling in SRA01/04 cells.

The prevalence and causes of visual impairment in an elderly Chinese Bai ethnic rural population: the Yunnan minority eye study.

PURPOSE To assess the prevalence and causes of visual impairment in the elderly Bai ethnic group in rural China. METHODS Random cluster sampling was used to identify the Bai ethnic group 50 years and older living in the Dali county of Yunnan, China. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) were measured using the Early Treatment Diabetic Retinopathy Study visual chart. Blindness and low vision were defined according to World Health Organization criteria. The major cause of visual impairment was identified for all participants who were visually impaired. RESULTS Of the 2742 eligible individuals, 2133 (77.8%) participated in the study, and 2115 (77.1%) had visual acuity data available. With the PVA, the prevalence of blindness and low vision was 3.59% and 15.22%, respectively. When the BCVA was used, these rates were reduced to 2.88% and 7.75%. Blindness and low vision were associated with older age and lack of education, but no sex difference was seen. Based on the BCVA, the predominant causes of blindness were cataract (70.5%), corneal opacity (8.2%), and glaucoma (6.6%). The majority of PVA-defined low vision cases were attributable to cataract (53.0%) and uncorrected refractive error (22.0%). CONCLUSIONS A higher rate of visual impairment was seen in this Bai nationality sample than has been reported from the Han nationality population in rural China. Since potentially treatable eye disease, cataract, and uncorrected refractive error were the most important causes of visual impairment in this population, affordable provision of surgery and low-vision rehabilitation programs would help to address this problem.