Willingness to pay for cataract surgery in baiyin district, northwestern China.

PURPOSE: To investigate willingness to pay for cataract surgery, and its associations, in Northwestern China. METHODS: Four hundred thirty-eight persons aged 50 years and above, diagnosed with cataract indicated for surgery, identified in an outreach screening program were included. Subjects were offered a willingness-to-pay interview for the maximal amount that the subjects would be willing to pay for a cataract surgery. Age, gender, literacy, education level, occupation, and annual household income were recorded. RESULTS: Among 328 (74.9%) subjects who completed the interview, 197 (60.1%) participants were willing to pay something for the cataract surgery (mean, 902.9 ± 856.7 renminbi[RMB], [US$ 145 ± 137]; median, 500RMB, US$ 78). Individuals with presenting visual acuity (PVA) in the worse eye ≤6/60 (OR: 2.1, 95% CI: 1.3-3.2) and a high annual household incomes (OR: 2.0, 95% CI: 0.9-4.6) were likely to be willing to pay for the surgery, as revealed in the regression models. Willingness to pay any amount for cataract surgery was more likely among literate persons (OR: 1.5, 95% CI: 1.0-2.4) and persons with non-agricultural occupation (OR: 1.8, 95% CI: 1.0-3.2). CONCLUSIONS: The amount that subjects were willing to pay is significantly less than the current cost of cataract surgery (5000 RMB, US$320) in the area. Providing low-cost cataract surgery to patients in a financially sustainable manner is important to increase uptake of cataract surgery among rural residents in Northwest China.

Chronic ocular hypertension in rabbits induced by limbal buckling.

AIM: To establish a rabbit model of chronic ocular hypertension (OHT) by limbal buckling. METHODS: Eighteen New Zealand White rabbits were involved and divided into three groups. A latex encircling band of 20, 25 or 35 mm was implanted behind the limbus in the right eye of each animal. The intraocular pressure (IOP) was monitored for 8 weeks, after which optic nerve damage was evaluated by fundus photography, optical coherence tomography (OCT) retrograde labelling and histology. Meanwhile, the anterior chamber angle (ACA) was examined by OCT and gonioscopy. RESULTS: OHT was induced in all animals after surgery. The IOP peaked at 38.0±3.7, 32.0±3.9 and 24.1±6.5 mm Hg in groups 1, 2 and 3, respectively, and remained elevated for 22, 25 and 39 days on average, respectively. The elevated IOPs showed good consistency within 2 weeks, although the durations of high IOP varied moderately. The area ratio between the optic cup and disc (cup to disc area) was increased in 73% of the treated eyes, and the average changes were 0.10±0.13, 0.11±0.08 and 0.09±0.02 in groups 1, 2 and 3, respectively. The depth of the optic cup was also increased in the treated eyes, and the density of the retinal ganglion cells was reduced. Additionally, the ACA showed a dynamic change with IOP after the latter was reduced by paracentesis. CONCLUSION: Limbal buckling provides an effective method of producing chronic OHT and glaucomatous optic neuropathy in rabbits.

Prevalence of visual impairment and outcomes of cataract surgery in Chaonan, South China.

PURPOSE: To estimate the prevalence and causes of blindness and visual impairment (VI), and report the outcomes of cataract surgery in Chaonan Region, Guangdong Province, southern China. DESIGN: Cross-sectional population-based survey. PARTICIPANTS: A total of 3484 participants including 1397 men (40.1%) and 2087 women (59.9%) aged ≥50 years were examined (94.2% response rate). METHOD: A two-stage cluster sampling procedure was used to select 3700 participants aged ≥50 years from 74 clusters of Chaonan Region. Participants were examined according to the Rapid Assessment of Avoidable Blindness (RAAB) method. Blindness and visual impairment (VI) were defined by the World Health Organization criteria. Participants with visual acuity (VA) < 6/18 in either eye were examined by ophthalmologists. The primary causes of blindness and VI were reported with reference to the participant's better eye. MAIN OUTCOME MEASURES: Prevalence and main causes of blindness, severe visual impairment (SVI), VI and the outcomes of cataract surgery. RESULTS: The standardized prevalence rates of blindness, SVI, and VI were 2.4% (95% confidence interval [CI], 1.9-2.9%), 1.0% (95% CI, 0.7-1.4%), and 6.4% (95% CI, 5.6%- 7.1%), respectively. The principal cause of blindness and SVI was cataract, accounting for 67.1% and 67.6% respectively, and the principal cause of VI was refractive error (46.9%). One hundred and fifty five out of 3484 (4.4%) people (211 eyes) had cataract surgery. Of the 211 eyes that had cataract surgery, 96.7% were pseudophakic. 67.2% of the 211 operated eyes had a presenting visual acuity (PVA) of 6/18 or better. CONCLUSIONS: The prevalence of blindness, SVI, and VI was high among rural residents in Chaonan. Cataract remained the leading cause of avoidable blindness. Outcomes of cataract surgery performed in rural private clinics were suboptimal. Quality-control initiatives such as hands-on training program should be introduced to improve cataract surgery outcomes.

Frequency doubling technology perimetry for detection of visual field progression in glaucoma: a pointwise linear regression analysis.

PURPOSE: We compared the detection of visual field progression and its rate of change between standard automated perimetry (SAP) and Matrix frequency doubling technology perimetry (FDTP) in glaucoma. METHODS: We followed prospectively 217 eyes (179 glaucoma and 38 normal eyes) for SAP and FDTP testing at 4-month intervals for ≥36 months. Pointwise linear regression analysis was performed. A test location was considered progressing when the rate of change of visual sensitivity was ≤-1 dB/y for nonedge and ≤-2 dB/y for edge locations. Three criteria were used to define progression in an eye: ≥3 adjacent nonedge test locations (conservative), any three locations (moderate), and any two locations (liberal) progressed. The rate of change of visual sensitivity was calculated with linear mixed models. RESULTS: Of the 217 eyes, 6.1% and 3.9% progressed with the conservative criteria, 14.5% and 5.6% of eyes progressed with the moderate criteria, and 20.1% and 11.7% of eyes progressed with the liberal criteria by FDTP and SAP, respectively. Taking all test locations into consideration (total, 54 × 179 locations), FDTP detected more progressing locations (176) than SAP (103, P < 0.001). The rate of change of visual field mean deviation (MD) was significantly faster for FDTP (all with P < 0.001). No eyes showed progression in the normal group using the conservative and the moderate criteria. CONCLUSIONS: With a faster rate of change of visual sensitivity, FDTP detected more progressing eyes than SAP at a comparable level of specificity. Frequency doubling technology perimetry can provide a useful alternative to monitor glaucoma progression.

Frequency-doubling technology perimetry for detection of the development of visual field defects in glaucoma suspect eyes: a prospective study.

IMPORTANCE: While standard automated perimetry (SAP) remains the reference standard for evaluation of visual field (VF) defects in glaucoma, this study demonstrates that frequency-doubling technology (FDT) perimetry is effective in monitoring visual field progression and may detect the onset of visual field defects earlier than SAP. OBJECTIVES: To compare detection of the development of VF defects, rate of change of VF loss, and risk factors for progression between SAP and matrix FDT perimetry in glaucoma suspect and ocular hypertensive eyes. DESIGN, SETTING, AND PARTICIPANTS: A total of 113 glaucoma suspect and ocular hypertensive eyes from 76 patients with normal SAP and FDT perimetry results at baseline were prospectively followed up for SAP and FDT perimetry testing at approximately 4-month intervals for 30 months or longer. Patients were consecutively enrolled and followed up from January 2, 2008, to February 28, 2012, at the Hong Kong Eye Hospital, Chinese University of Hong Kong. Visual field progression was defined by the development of VF defects confirmed by 3 or more consecutive examinations at a cluster of 3 or more (less conservative) or 4 or more (more conservative) locations. The rates of change of mean deviation and pattern standard deviation were evaluated with linear mixed models and the risk factors for VF progression were computed with Cox proportional hazard models. RESULTS: During a median study period of 3.4 years, 8.0% of eyes developed VF defects detected by FDT perimetry, 6.2% by SAP, and 4.4% by both using the less-conservative criteria. The detection dropped to 6.2%, 4.4%, and 2.7%, respectively, when the more-conservative criteria were applied. The rate of change of pattern standard deviation was significantly faster for FDT perimetry than SAP (P < .001). Baseline average retinal nerve fiber layer thickness and the number of clock hours of abnormal retinal nerve fiber layer measurement were associated with increased risk for VF progression for both SAP and FDT perimetry. CONCLUSIONS AND RELEVANCE: Frequency-doubling technology perimetry would be useful to monitor the onset of VF defects in glaucoma and may detect VF defects not evident in SAP.

Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: interpreting the RNFL maps in healthy myopic eyes.

PURPOSE: To investigate the association between the distribution profile of the retinal nerve fiber layer (RNFL) bundles and myopia and its impact on interpretation of the RNFL map imaged by a spectral-domain optical coherence tomography (SD-OCT). METHODS: the RNFL of 189 myopic eyes from 103 normal healthy myopic participants was imaged by an SD-OCT. The angle between the long axes of the superotemporal and inferotemporal RNFL bundles determined in the RNFL thickness map (the RNFL distribution angle) and the abnormal area in the RNFL thickness deviation map were measured. The associations between the RNFL distribution angle and the axial length/spherical error, and between the area of abnormal RNFL measurement and each of the following: axial length, spherical error, RNFL distribution angle, average RNFL thickness, optic disc area, and signal strength were analyzed with linear mixed models. RESULTS: The RNFL distribution angle decreased with the axial length (P < 0.011). In the univariate analysis, the area of abnormal RNFL measurement was positively associated with the axial length (P = 0.001); and negatively associated with the RNFL distribution angle (P < 0.001), average RNFL thickness (P < 0.001), optic disc area (P ≤ 0.001), and signal strength (P = 0.026). In the multivariate analysis, the area of abnormal RNFL measurement was negatively associated with the RNFL distribution angle independent of other covariates. CONCLUSIONS: The superotemporal and inferotemporal RNFL bundles converged temporally with increasing myopia, which was associated with an increase in area of abnormal RNFL measurement. The interpretation of the RNFL thickness map in myopic eyes requires careful consideration of the distribution pattern of the RNFL bundles.

Tracking retinal microgliosis in models of retinal ganglion cell damage.

PURPOSE: To investigate the longitudinal profiles of microgliosis after optic nerve injury induced by optic nerve crush and acute elevation of intraocular pressure (IOP). METHODS: A confocal scanning laser ophthalmoscope was used to image the retinal microglia of the CX3CR1(GFP/+) transgenic mice in vivo at baseline, 3 days and then weekly for 4 weeks after optic nerve crush (n = 3), and after elevating the IOP to 110 mm Hg for 30 (n = 3) or 60 (n = 3) minutes. RESULTS: After optic nerve crush, the density of microglia increased by 2.43 ± 0.19-fold at week 1 and then gradually declined with 2.04 ± 0.24-, 1.69 ± 0.25-, and 1.29 ± 0.11-fold increases at week 2, 3, and 4, respectively. Microgliosis followed a similar pattern after acute IOP elevation and the increase in microglia was associated with the duration of IOP elevation. There were 1.35 ± 0.17- and 2.03 ± 0.08-fold increases in microglia at week 1, and 1.15 ± 0.11- and 1.11 ± 0.10-fold increases at week 4, after 30 and 60 minutes of acute IOP elevation, respectively. The morphology of microglia changed from ramified to ameboid form in 1 week, and then returned to ramified form in the subsequent weeks. There was a significant negative association between the number of surviving retinal ganglion cells (RGCs) and the extent of microgliosis during the follow-up period (R² = 0.72, P = 0.004). CONCLUSIONS: Longitudinal in vivo imaging of the retinal microglia can provide an effective approach to study microgliosis and its association with RGC degeneration.

Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: patterns of retinal nerve fiber layer progression.

OBJECTIVE: To examine the use of the retinal nerve fiber layer (RNFL) thickness map generated by a spectral-domain optical coherence tomography (OCT) to detect RNFL progression and identify the pattern of progressive changes of RNFL defects in glaucoma. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred eighty-six eyes of 103 glaucoma patients. METHODS: Patients were followed at 4-month intervals for ≥ 36 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) and had visual field testing at the same visits. We defined RNFL progression by Guided Progression Analysis (Carl Zeiss Meditec) of serial RNFL thickness maps. The pattern of RNFL progression was evaluated by comparing the baseline RNFL thickness deviation map and the RNFL thickness change map. Visual field progression was defined by trend analysis of visual field index and event analysis based on the Early Manifest Glaucoma Trial criteria. MAIN OUTCOME MEASURES: The presence and the pattern of RNFL progression. RESULTS: A total of 2135 OCT images were reviewed. Twenty-eight eyes (15.1%) from 24 patients (23.3%) had RNFL progression detected by RNFL thickness map analysis. Three RNFL progression patterns were observed: (1) widening of RNFL defects (24 eyes, 85.7%), (2) deepening of RNFL defects (2 eyes, 7.1%, both had concomitant widening of RNFL defects), and (3) development of new RNFL defects (5 eyes, 17.9%). The inferotemporal meridian (324°-336°) 2.0 mm away from the optic disc center was the most frequent location where RNFL progression was detected. Thirteen eyes (46.4%) had concomitant visual field progression; 61.5% (n = 8) of these had RNFL progression that preceded or occurred concurrently with visual field progression. Forty-two eyes from 37 patients (22.6%) had visual field progression by trend and/or event analyses without progression in the RNFL thickness map. CONCLUSIONS: Analysis of serial RNFL thickness maps generated by the spectral-domain OCT facilitates the detection of RNFL progression in glaucoma.

Optic disc imaging with spectral-domain optical coherence tomography: variability and agreement study with Heidelberg retinal tomograph.

OBJECTIVE: To evaluate the agreement of optic disc measurements obtained with the Cirrus high-density optical coherence tomography (HD-OCT) and the Heidelberg retina tomograph (HRT) and compare the intervisit, test-retest variability between the instruments. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Two hundred seven subjects (109 glaucoma and 98 normal subjects). METHODS: One eye from each individual was selected randomly for optic disc imaging by the Cirrus HD-OCT and the HRT. Areas of the optic disc and the cup, cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio were compared between the instruments. The OCT measurements were corrected for ocular magnification using the Littman's formula. The measurement agreement was evaluated with the Bland-Altman plots. The intervisit test-retest variability was examined in 17 randomly selected glaucoma patients who underwent optic disc imaging weekly for 8 consecutive weeks. The intraclass correlation coefficients (ICC) and the reproducibility coefficients of the optic disc parameters were computed. MAIN OUTCOME MEASURES: Measurement agreement, reproducibility coefficients, and ICCs of optic disc parameters. RESULTS: The OCT measured smaller optic disc and rim areas and greater cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio than the HRT did (all with P<0.001). There were proportional biases in the Bland-Altman plots between OCT and HRT optic disc measurements except for rim area and cup-to-disc area ratio. The 95% limits of agreement of rim area ranged between -0.28 and 0.88 mm(2) before, and between -0.22 and 0.92 mm(2) after correction for ocular magnification. Both OCT and HRT showed high test-retest reproducibility with ICCs ≥ 0.921. Although the reproducibility coefficient of OCT rim area (0.093 mm(2); 95% confidence interval [CI], 0.081-0.105 mm(2)) was significantly smaller than that of the HRT (0.186 mm(2); 95% CI, 0.163-0.210 mm(2); P = .018), there were no differences in the ICCs between the instruments. CONCLUSIONS: Optic disc assessment by spectral-domain OCT and confocal scanning laser ophthalmoscopy demonstrates poor agreement but similarly low test-retest variability. The source of their disagreement and its effects on the detection of progression require further study.

A rabbit model of age-dependant ocular hypertensive response to topical corticosteroids.

OBJECTIVE: To investigate the ocular hypertensive response to topical dexamethasone (DEX), rimexolone (RIM), loteprednol etabonate (LOT) and fluorometholone (FML) in rabbits of different ages. METHODS: Seventy-five rabbits of three age groups (7 weeks, 6 months and 1-year old) received topical administration of 0.1% DEX, 1% RIM, 0.5% LOT, 0.1% FML or balanced salt solution four times daily for 1 month. Intraocular pressure (IOP) was monitored at regular time intervals. After a month, eyes were harvested for histological study with haematoxylin and eosin (H&E), periodic acid Schiff and Masson trichrome staining. Trabecular meshwork changes were graded by masked ocular pathologists. RESULTS: Topical DEX caused the greatest increase in IOP, followed by RIM and FML. LOT caused the least IOP increase. Similar pattern of IOP response to the four corticosteroids was observed in the three studied age groups. Young rabbits (7 week) were the most responsive to corticosteroids among the age groups. Extracellular matrix thickening in the trabecular meshwork region and loss of trabecular meshwork cells were observed after DEX, FML or RIM treatments. CONCLUSION: Young rabbits are more susceptible to steroid induced increase in IOP, even for milder steroids such as fluorometholone and rimexolone.

Computer simulation of progressive retinal nerve fiber layer loss in glaucoma: performance of event and trend analyses.

PURPOSE: Although event analysis (EA) and trend analysis (TA) have been widely adopted to evaluate glaucoma progression in clinical trials, there is poor agreement between the strategies and no consensus on strategy selection in clinical practice. With computer simulation of progressive loss of the retinal nerve fiber layer (RNFL), the authors compared the performance of TA and EA for the detection of glaucoma progression. METHODS: RNFL progression was modeled with reference to the individual's test-retest variability and the pattern and rate of progression. The sensitivity and specificity of each scenario were computed from 5000 simulated datasets. Simulation results were validated with longitudinal RNFL measurements obtained from 107 glaucoma and glaucoma suspect patients who had a median follow-up period of 38 months. RESULTS: TA generally attained a sensitivity ≥80% earlier than EA, although EA with a group reproducibility coefficient had a higher sensitivity than TA for eyes with a large test-retest variability in the early follow-up period, albeit at a lower specificity. The specificity of TA was 95% and ranged between 80% and 100% for EA. Independent of test-retest variability and the pattern and rate of progression, TA had an accuracy ≥80% earlier than EA. In the longitudinal study, the detection rate was 42%, 35%, and 3% for TA, whereas it was 11% to 40%, 12% to 28%, and 3% to 23% for EA at 36 months of follow-up in eyes with small, average, and large test-retest variabilities, respectively. CONCLUSIONS: Although test-retest variability is an important determinant in progression analysis, TA generally outperformed EA for the detection of RNFL progression in glaucoma.

Measurement of photoreceptor layer in glaucoma: a spectral-domain optical coherence tomography study.

Objective. To measure and compare photoreceptor layer thickness between normal and glaucomatous eyes using spectral-domain optical coherence tomography (OCT). Methods. Thirty-eight healthy normal volunteers and 47 glaucoma patients were included in the analysis. One eye from each participant was randomly selected for macula imaging by a spectral-domain OCT (3D OCT-1000, Topcon, Tokyo, Japan). The foveal and parafoveal (1.5 mm from the fovea) outer nuclear layer (ONL) and inner and outer segments (IS+OS) layer thicknesses were measured by a single masked observer. The measurements were repeated 3 times in a random sample of 30 normal eyes to determine the repeatability coefficient and intraclass correlation coefficient. Results. The measurement variabilities of photoreceptor thickness were low. The respective intraclass correlation coefficients of ONL and IS+OS thicknesses were 0.96 (95% confidence interval: 0.94-0.98) and 0.82 (95% confidence interval 0.70-0.90). While there were no differences in parafoveal ONL and IS+OS thicknesses between normal and glaucoma groups (P ≤ .410), the foveal ONL thickness was greater in glaucomatous eyes (P = .011) than in normal eyes. Conclusions. Glaucomatous damage may involve structural change in the photoreceptor layer.

Comparison of standard automated perimetry, frequency-doubling technology perimetry, and short-wavelength automated perimetry for detection of glaucoma.

PURPOSE: To compare the performance of standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and short-wavelength automated perimetry (SWAP) in detecting glaucoma. METHODS: One hundred thirty-two eyes of 95 glaucoma patients and 37 normal subjects had retinal nerve fiber layer (RNFL) imaging and visual field testing by SAP, Matrix FDT perimetry, and Swedish interactive thresholding algorithm (SITA) SWAP at the same visit (all perimeters by Carl Zeiss Meditec, Inc., Dublin, CA). Visual field defects were confirmed with two or more consecutive examinations by the same types of perimetry. Glaucoma was defined with the reference to the RNFL thickness deviation map score (≥ 4, glaucomatous; ≤ 2, normal). The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of MD (mean deviation) and PSD (pattern standard deviation) of the perimetries were compared. RESULTS: Taking all glaucoma patients into consideration, the sensitivity was highest for Matrix FDT perimetry (69%), followed by SAP (68%), and then SITA SWAP (59%). When the analysis included only patients with early glaucoma, the sensitivity decreased to 52%, 46%, and 34%, respectively, with a significant difference detected between Matrix FDT perimetry and SITA SWAP (P = 0.034). The specificity was ≥ 97% for all perimetries. The AUCs of MD and PSD followed a similar order, with Matrix FDT perimetry having the greatest AUC (0.89-0.94), followed by SAP (0.87-0.94), and then SITA SWAP (0.69-0.90). There were significant differences in sensitivities at 90% specificity between Matrix FDT perimetry and SITA SWAP (P ≤ 0.005 for MD; P ≤ 0.039 for PSD). CONCLUSIONS: The performance for glaucoma detection was comparable between FDT perimetry and SAP. FDT perimetry had a higher sensitivity for detecting glaucoma than did SWAP at a comparable level of specificity.

Diagnostic classification of retinal nerve fiber layer measurement in myopic eyes: a comparison between time-domain and spectral-domain optical coherence tomography.

PURPOSE: To evaluate and compare the diagnostic classification of retinal nerve fiber layer (RNFL) measurement between time-domain and spectral-domain optical coherence tomography (OCT) in myopic eyes. DESIGN: Prospective, observational study. METHODS: A total of 97 eyes from 97 healthy myopic subjects were included. The RNFL in each eye was imaged sequentially with the Stratus OCT and the Cirrus HD-OCT (Carl Zeiss Meditec). With reference to the built-in normative database, the number of abnormal diagnostic classifications (borderline or outside normal limits) in each OCT device was analyzed and compared using the likelihood ratio chi-square test. Multiple logistic regression analysis was performed to evaluate factors associated with abnormal diagnostic classification. RESULTS: The Cirrus HD-OCT classified a significantly higher percentage of eyes as outside normal limits/borderline in at least 1 clock hour (Stratus, 14.4%/24.8%; Cirrus, 21.6%/34.1%; all P < .01). RNFL measurement at 1 (23.6%) and 2 o'clock (23.5%) of all eyes was the most frequent location classified as abnormal by the Cirrus HD-OCT and the Stratus OCT, respectively. Eyes with smaller optic disc and longer axial length were more likely to have abnormal diagnostic classification. CONCLUSIONS: In myopic eyes, Cirrus HD-OCT was more likely to have abnormal diagnostic classification than the Stratus OCT.

Tracking dendritic shrinkage of retinal ganglion cells after acute elevation of intraocular pressure.

PURPOSE: To investigate dendritic changes of retinal ganglion cells (RGCs) and the rate of dendritic shrinkage after retinal ischemia induced by acute elevation of intraocular pressure (IOP). METHODS: After elevating the IOP to 110 mm Hg for 30, 60, 90, and 120 minutes, a confocal scanning laser ophthalmoscope (CSLO) was used to serially image the retinas of the Thy-1 YFP transgenic mice in vivo for 1 to 3 months. Dendritic and axonal arborizations of 52 RGCs were visualized and followed longitudinally. Dendritic field, dendritic branching complexity (modified Sholl analysis), axonal diameter, and cell body area were measured. A total of 426 longitudinal measurements of dendritic field and dendritic complexity were analyzed for estimation of rate of change with linear mixed modeling. RESULTS: There were no morphologic changes of RGCs after 30 (n = 12) or 60 (n = 12) minutes of ischemia. After 90 minutes of ischemia (n = 19), 78.9% of RGCs showed progressive loss of dendrites, axon, and cell body, 5.3% had only mild reduction of branching complexity and shrinkage of dendritic field whereas 15.8% showed no morphologic changes. All RGCs lost dendritic and axonal arborizations after 120 minutes of ischemia (n = 9). The rates of reduction of dendritic field were 11.7% per day (95% confidence interval, 5.0%-18.4% per day) after 90 minutes, and 15.1% per day (10.3%-19.9% per day) after 120 minutes of ischemia. CONCLUSIONS: RGCs demonstrated dendritic shrinkage after 90 to 120 minutes, but not after 30 to 60 minutes of ischemia. In vivo imaging of dendritic changes could provide a sensitive approach to measure the rate of dendritic shrinkage after acute IOP elevation.

MicroRNA-145 regulates human corneal epithelial differentiation.

BACKGROUND: Epigenetic factors, such as microRNAs, are important regulators in the self-renewal and differentiation of stem cells and progenies. Here we investigated the microRNAs expressed in human limbal-peripheral corneal (LPC) epithelia containing corneal epithelial progenitor cells (CEPCs) and early transit amplifying cells, and their role in corneal epithelium. METHODOLOGY/PRINCIPAL FINDINGS: Human LPC epithelia was extracted for small RNAs or dissociated for CEPC culture. By Agilent Human microRNA Microarray V2 platform and GeneSpring GX11.0 analysis, we found differential expression of 18 microRNAs against central corneal (CC) epithelia, which were devoid of CEPCs. Among them, miR-184 was up-regulated in CC epithelia, similar to reported finding. Cluster miR-143/145 was expressed strongly in LPC but weakly in CC epithelia (P = 0.0004, Mann-Whitney U-test). This was validated by quantitative polymerase chain reaction (qPCR). Locked nucleic acid-based in situ hybridization on corneal rim cryosections showed miR-143/145 presence localized to the parabasal cells of limbal epithelium but negligible in basal and superficial epithelia. With holoclone forming ability, CEPCs transfected with lentiviral plasmid containing mature miR-145 sequence gave rise to defective epithelium in organotypic culture and had increased cytokeratin-3/12 and connexin-43 expressions and decreased ABCG2 and p63 compared with cells transfected with scrambled sequences. Global gene expression was analyzed using Agilent Whole Human Genome Oligo Microarray and GeneSpring GX11.0. With a 5-fold difference compared to cells with scrambled sequences, miR-145 up-regulated 324 genes (containing genes for immune response) and down-regulated 277 genes (containing genes for epithelial development and stem cell maintenance). As validated by qPCR and luciferase reporter assay, our results showed miR-145 suppressed integrin ß8 (ITGB8) expression in both human corneal epithelial cells and primary CEPCs. CONCLUSION/SIGNIFICANCE: We found expression of miR-143/145 cluster in human corneal epithelium. Our results also showed that miR-145 regulated the corneal epithelium formation and maintenance of epithelial integrity, via ITGB8 targeting.

Genetic variants at 13q12.12 are associated with high myopia in the Han Chinese population.

High myopia, which is extremely prevalent in the Chinese population, is one of the leading causes of blindness in the world. Genetic factors play a critical role in the development of the condition. To identify the genetic variants associated with high myopia in the Han Chinese, we conducted a genome-wide association study (GWAS) of 493,947 SNPs in 1088 individuals (419 cases and 669 controls) from a Han Chinese cohort and followed up on signals that were associated with p < 1.0 × 10(-4) in three independent cohorts (combined, 2803 cases and 5642 controls). We identified a significant association between high myopia and a variant at 13q12.12 (rs9318086, combined p = 1.91 × 10(-16), heterozygous odds ratio = 1.32, and homozygous odds ratio = 1.64). Furthermore, five additional SNPs (rs9510902, rs3794338, rs1886970, rs7325450, and rs7331047) in the same linkage disequilibrium (LD) block with rs9318086 also proved to be significantly associated with high myopia in the Han Chinese population; p values ranged from 5.46 × 10(-11) to 6.16 × 10(-16). This associated locus contains three genes-MIPEP, C1QTNF9B-AS1, and C1QTNF9B. MIPEP and C1QTNF9B were found to be expressed in the retina and retinal pigment epithelium (RPE) and are more likely than C1QTNF9B-AS1 to be associated with high myopia given the evidence of retinal signaling that controls eye growth. Our results suggest that the variants at 13q12.12 are associated with high myopia.

Evaluation of retinal nerve fiber layer progression in glaucoma: a comparison between spectral-domain and time-domain optical coherence tomography.

OBJECTIVE: To compare the performance of a spectral-domain optical coherence tomography (OCT) device and a time-domain OCT device to detect retinal nerve fiber layer (RNFL) progression in glaucoma patients. DESIGN: Prospective study. PARTICIPANTS: One hundred twenty-eight eyes of 81 glaucoma patients. METHODS: Patients were followed up at 4-month intervals for at least 24 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA) and the Stratus OCT (Carl Zeiss Meditec, Inc.) and underwent visual field testing at the same visit. Linear regression analyses between circumpapillary RNFL measurements (average, superior, and inferior RNFL thicknesses), visual field index (VFI), and follow-up time were performed. RNFL progression and RNFL improvement were identified when a significant negative or positive trend was detected, respectively. The agreement between the OCT instruments for progression detection was analyzed with κ statistics. MAIN OUTCOME MEASURES: Number of eyes with RNFL progression and improvement, agreement of progression detection between RNFL measurements and VFI, and rate of change of average RNFL thickness. RESULTS: Twenty-two eyes (19 patients) and 4 eyes (4 patients) had progression, and 0 and 5 eyes (5 patients) had improvement detected by the Cirrus HD-OCT and the Stratus OCT average RNFL measurements, respectively. The agreement for detection of RNFL progression was poor between the 2 OCT instruments (κ = 0.188, 0.027, and 0.267 for average, superior, and inferior RNFL thicknesses, respectively). The respective agreement between VFI and average RNFL thickness progression determined by the Cirrus HD-OCT and the Stratus OCT was 0.125 and 0.047. The rate of average RNFL thickness progression ranged between -1.52 µm/year and -5.03 µm/year for the Cirrus HD-OCT and between -2.22 µm/year and -7.60 µm/year for the Stratus OCT. CONCLUSIONS: The Cirrus HD-OCT outperformed the Stratus OCT in detecting more eyes with RNFL progression and fewer eyes with RNFL improvement. Because of reduced measurement variability, the Cirrus HD-OCT could detect changes in RNFL thickness sooner than the Stratus OCT. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.