Effect of corneal incision features on anterior and posterior corneal astigmatism and higher-order aberrations after cataract surgery.

PURPOSE: To evaluate the influence of 2.2 mm clear corneal incision (CCI) features in surgically induced astigmatism (SIA) and higher-order aberrations (HOAs) after cataract surgery. METHODS: Right eyes of 92 subjects receiving 2.2 mm incision cataract surgery were involved. A total of 38 eyes were categorized as the intact incision group, and 54 eyes were the defective incision group. Pre- and postoperative (1 month and 6 months) corneal astigmatism and HOAs on anterior and posterior corneal surfaces, corneal volume, and corneal thickness (CT) were measured using Pentacam. The CCI features including incision length (IL), incision angles, distance from incision to central cornea (Dis-En/Ex), and CT at incision site were quantified using AS-OCT. RESULTS: The defective incision group showed shorter IL and larger incision angles [false discovery rate (FDR) - p < 0.05]. Changes in CT at incision site were more pronounced for the defective incision group (FDR - p < 0.05). Some SIA parameters were related to the certain specific CCI features, especially IL (FDR - p < 0.05). Both groups exhibited significant increased 6 mm posterior corneal tHOAs at 1 month (Bonferroni corrected - p < 0.01) and the defective incision group showed increased 6 mm posterior tHOAs at 6 months (Bonferroni corrected - p = 0.023). There were characteristic correlations between Zernike terms and CCI features including IL, CT, Dis-En/Ex, and incision angles at 1 month, especially over 6 mm zone. CONCLUSION: The CCI deformities can affect corneal recovery and induce more HOAs at 1 month postoperatively. Such effects became minor, but could persist until 6 months. The IL combined with Angle-En/Ex was important factor influencing CCI integrity and corneal optical quality.

SARI prevents ocular angiogenesis and inflammation in mice.

SARI (Suppressor of AP-1, regulated by IFN-ß) is known to play an important role in some systemic disease processes such an inflammatory conditions and cancer. We hypothesize that SARI may also play a role in ocular diseases involving inflammation and neovascularization. To explore our hypothesis, further, we investigated an endotoxin-induced uveitis (EIU) and experimental argon laser-induced choroidal neovascularization (CNV) model in SARI wild-type (SARIWT ) and SARI-deficient (SARI-/- ) mice. Through imaging, morphological and immunohistochemical (IHC) studies, we found that SARI deficiency exacerbated the growth of CNV. More VEGF-positive cells were presented in the retina of SARI-/- mice with CNV. Compared to SARIWT  mice, more inflammatory cells infiltrated the ocular anterior segment and posterior segments in SARI-/- mice with EIU. Collectively, the results point to a potential dual functional role of SARI in inflammatory ocular diseases, suggesting that SARI could be a potential therapy target for ocular inflammation and neovascularization.

Effects of Lead Phytochemicals of Radix Scutellariae on Acanthamoeba.

Purpose: Acanthamoeba keratitis (AK), which is associated with noncompliant use of contact lenses, remains difficult to treat due to delayed diagnosis and paucity of therapeutic agents. Although improvements in activity against Acanthamoeba infection have been achieved in disinfecting solutions for soft contact lenses, such modifications have not been extended to those for special rigid gas permeable (RGP) contact lenses, which are increasingly used for myopia control in children. Phytochemicals present in herbs used for traditional Chinese medicine may be effective as therapeutic or preventive agents. The purpose of this study was to investigate amoebicidal properties of lead phytochemicals of Radix scutellariae alone and in combination with multipurpose (disinfecting) solutions (MPS) for RGP lenses. Methods: Viability of Acanthamoeba castellani and A. polyphaga trophozoites was determined following exposure to four phytochemicals: baicalin, baicalein, wogonoside, and oroxylin A and both alone and in combination with four RGP MPS, using a modified stand-alone technique. Results: As individual agents, wogonoside and oroxylin A showed highest activity against A. castellani and A. polyphaga trophozoites, respectively. For both organisms, the combination of baicalein and oroxylin A was superior. Effectiveness of MPS alone did not exceed 0.27 log reduction, but addition of combined baicalein and oroxylin A resulted in 0.92 and 0.64 log reductions of A. castellani and A. polyphaga, respectively. Conclusions: The combination of baicalein and oroxylin A enhanced the activity of MPS for RGP contact lenses against trophozoites of two pathogens, A. castellani, and A. polyphaga, and offers a potential therapeutic and/or preventative agent for AK.

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia.

Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.

Genetic susceptibility to refractive error: association of vasoactive intestinal peptide receptor 2 (VIPR2) with high myopia in Chinese.

Myopia is the most common ocular disease worldwide. We investigated the association of high myopia with the common single nucleotide polymorphisms (SNPs) of five candidate genes - early growth response 1 (EGR1), v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS), jun oncogene (JUN), vasoactive intestinal peptide (VIP), and vasoactive intestinal peptide receptor 2 (VIPR2). We recruited 1200 unrelated Chinese subjects with 600 cases (spherical equivalent ≤-8.00 diopters) and 600 controls (spherical equivalent within ±1.00 diopter). A discovery sample set was formed from 300 cases and 300 controls, and a replication sample set from the remaining samples. Tag SNPs were genotyped for the discovery sample set, and the most significant haplotypes and their constituent SNPs were followed up with the replication sample set. The allele and haplotype frequencies in cases and controls were compared by logistic regression adjusted for sex and age to give P a values, and multiple comparisons were corrected by permutation test to give P aemp values. Odd ratios (OR) were calculated accordingly. In the discovery phase, EGR1, JUN and VIP did not show any significant association while FOS and VIPR2 demonstrated significant haplotype association with high myopia. In the replication phase, the haplotype association for VIPR2 was successfully replicated, but not FOS. In analysis combining both sample sets, the most significant association signals of VIPR2 were the single marker rs2071625 (P a = 0.0008, P aemp = 0.0046 and OR = 0.75) and the 4-SNP haplotype window rs2071623-rs2071625-rs2730220-rs885863 (omnibus test, P a = 9.10e-10 and P aemp = 0.0001) with one protective haplotype (GGGG: P aemp = 0.0002 and OR = 0.52) and one high-risk haplotype (GAGA: P aemp = 0.0027 and OR = 4.68). This 4-SNP haplotype window was the most significant in all sample sets examined. This is the first study to suggest a role of VIPR2 in the genetic susceptibility to high myopia. EGR1, JUN, FOS and VIP are unlikely to be important in predisposing humans to high myopia.

Screening for diabetic retinopathy with or without a copayment in a randomized controlled trial: influence of the inverse care law.

OBJECTIVE: To examine whether the inverse care law operates in a screening program for diabetic retinopathy (DR) based on fee for service in Hong Kong. DESIGN: Randomized controlled trial. PARTICIPANTS: All those with type 1 or 2 diabetes from 2 clinics were recruited. INTERVENTION: Diabetic retinopathy screening with a small copayment versus free access in a publicly funded family medicine service. MAIN OUTCOME MEASURES: Uptake of screening and severity of DR detected. Association between these outcome variables and independent variables were determined using multivariate logistic regression models and reported as odds ratios (ORs). RESULTS: After randomization, 1387 subjects in the free group and 1379 subjects in the pay group were eligible for screening, and 94.9% (1316/1387) and 92.6% (1277/1379), respectively, agreed to participate in the study. The offer of screening was accepted by 94.8% (1247/1316) in the free group and 91.2% (1164/1277) in the pay group, and the final uptake ratios were 88.5% (1165/1316) and 82.4% (1052/1277), respectively (Pearson chi = 19.74, P<0.001). Being in the pay group was associated with a lower uptake of screening than being in the free group (OR, 0.59; confidence interval [CI], 0.47-0.74) and a lower detection rate of DR (OR, 0.73; CI, 0.60-0.90) after adjustment for potential confounding factors. Subjects with higher socioeconomic status were more likely to attend screening and had a lower prevalence of DR detected. CONCLUSIONS: The inverse care law seems to operate in a preventive intervention when a relatively small copayment is applied. There is a case for making effective preventive services free of charge. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of IGF1 gene haplotypes with high myopia in Chinese adults.

OBJECTIVE: To investigate the association of high myopia with common single-nucleotide polymorphisms (SNPs) in the IGF1, IGFBP3, and IGFBP4 genes in a Chinese population. METHODS: For our case-control study, we recruited 600 unrelated participants: 300 case participants with high myopia (-8.00 diopters or less) and 300 emmetropic controls (within ±1.00 diopter). Twenty-one tag SNPs were selected from these candidate genes and were genotyped. Genotype data were analyzed by logistic regression. Multiple comparisons were corrected by running 15 000 permutations of case-control status. RESULTS: Although we did not find any significant association for IGF1 SNPs using single-marker analysis, we identified many windows with haplotype frequencies significantly different between case participants and control participants using a variable-sized sliding-window strategy. In particular, the most significant association was shown by a 3-SNP window consisting of rs12423791, rs7956547, and rs5742632 (omnibus test: asymptotic P(asym) = 3.70 × 10(-9) and empirical P(emp) = 6.67 × 10(-5)). There were 3 high-risk haplotypes: CAC (P(asym) = 2.35 × 10(-6); odds ratio [OR], 5.06), GAT (P(asym) = 3.56 × 10(-4); OR, 3.18), and GGC (P(asym) = 2.25 × 10(-3); OR, 25.10). There was 1 protective haplotype: GAC (P(asym) = 8.43 × 10(-4); OR, 0.63). On the other hand, our single-marker and haplotype analyses did not show any significant association for IGFBP3 and IGFBP4. CONCLUSIONS: IGF1 haplotypes are associated with genetic susceptibility to high myopia in Chinese adults, whereas IGFBP3 and IGFBP4 are unlikely to be important in the genetic predisposition to high myopia. CLINICAL RELEVANCE: IGF1 is associated with high myopia, and identifying the causal variants is important for understanding the underlying mechanisms.

Incidence of diabetic retinopathy in a Hong Kong Chinese population.

BACKGROUND: The aim was to examine the progression and regression of diabetic retinopathy within a four-year period in a Chinese population with type 2 diabetes mellitus in a community optometry clinic in Hong Kong. METHODS: During the period May 2005 to November 2009, 5,160 patients with type 2 diabetes mellitus who had attended at least two diabetic retinopathy screening sessions at a community optometry clinic were included as subjects in this study. All had retinal photographs taken of both eyes, which were of sufficiently good quality for grading. For the purpose of this study, diabetic retinopathy grading was based on the results of the worst eye. The main outcomes were the within four-year incidence of diabetic retinopathy and the incidence of progression and regression of diabetic retinopathy. RESULTS: Of the 5,160 subjects in this study, 3,647 had no diabetic retinopathy, while 1,513 had diabetic retinopathy at the baseline visit. Of those 3,647 subjects with no diabetic retinopathy, the within four-year cumulative incidence of any diabetic retinopathy, mild or moderate non-proliferative diabetic retinopathy and sight-threatening diabetic retinopathy was 15.16 per cent, 14.45 per cent, 0.69 per cent and 0.03 per cent, respectively. Of those 1,513 subjects with diabetic retinopathy at baseline, the within four-year progression incidence of diabetic retinopathy was 6.61 per cent and the regression incidence of diabetic retinopathy was 45.54 per cent. CONCLUSION: The high regression incidence of diabetic retinopathy suggests that it might not be necessary for all patients with diabetes to be screened annually. Other methods to determine the screening frequency for an individual patient should be explored.

Community-based diabetic retinopathy screening in Hong Kong: ocular findings.

BACKGROUND: Diabetic retinopathy is one of the most common causes of blindness. Timely retinal evaluation is known to prevent or minimise visual loss. This study compared the prevalence of ocular disorders in patients who have and have not undergone a retinal examination since diagnosis of their type 2 diabetes mellitus (T2DM). Such data might be useful for planning purposes by health care authorities and agencies in Hong Kong. METHODS: Patients with T2DM aged 30 years or over presented for standardised interviews and screening for diabetic retinopathy. The presence of ocular disorders was recorded and the severity of the retinopathy, if any, was graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) classification. RESULTS: For the 1058 subjects who participated in this study, the mean age at examination was 61.8 ± 10.5 (SD) years (range, 31-93 years). For the 891 subjects with known diabetes for one year or longer, 62.7 per cent had never undergone an evaluation for diabetic retinopathy since diagnosis of their T2DM. Of the 891 subjects, gradable fundus photographs were available for 853 subjects and nearly 2.0 per cent of these had sight-threatening retinopathy based on the ETDRS classification. Those who had not had an eye examination since diagnosis of their T2DM were more likely to have sight-threatening retinopathy than those who had a retinal evaluation (2.6 versus 0.6 per cent; p = 0.04). CONCLUSION: In our sample, over 60 per cent of patients with T2DM for one year or longer had not had a retinal assessment since diagnosis. The risk of developing sight-threatening diabetic retinopathy appears to be higher for those who have not had a retinal assessment.

Correctable visual impairment among people with diabetes in Hong Kong.

BACKGROUND: the prevalence of visual impairment is known to be higher in a diabetic population than in a non-diabetic population. How much of this visual impairment may be attributed to uncorrected refractive error is unclear. This study examined the prevalence of visual impairment in a Hong Kong diabetic population to determine the proportion of the visual impairment that could be corrected with prescription spectacles. METHODS: patients with type 2 diabetes mellitus (T2DM) were recruited as subjects for this study. All subjects underwent a standardised diabetic retinopathy screening that included measurement of presenting distant vision, biomicroscopic examination of the anterior eye and a retinal examination. For those subjects whose visual acuity was worse than 6/9.5, autorefraction was performed. In this study, we classified visual impairment into three categories: no visual impairment (visual acuity in the better eye better than or equal to 6/18), mild visual impairment (visual acuity in the better eye between 6/18 and 6/60) and severe visual impairment (visual acuity in the better eye less than or equal to 6/60). RESULTS: for the 2,301 subjects who participated in this study, the mean age at examination was 61.4 ± 10.5 years (range, 23 to 92 years). Regarding visual acuity, 11.3 per cent (259/2,301) of subjects had visual impairment with 10.6 per cent being mild (244/2,301) and 0.7 per cent severe (15/2,301). After correction with a prescription determined by autorefraction, the prevalence of visual impairment dropped to 4.0 per cent (91/2,301). Nearly 70 per cent (168/259) of visual impairment was correctable by prescription spectacles and 21.6 per cent (56/259) of subjects were likely to benefit from cataract surgery. CONCLUSION: for our sample of diabetic patients, nearly 70 per cent of the visual impairment could be remedied by a spectacle correction. In the care of the diabetic eye, eye-care providers should not focus solely on diabetic retinopathy. The quality of life in people with T2DM can be improved simply by eliminating uncorrected refractive errors.

Comparing the multifocal electroretinogram topography before and after cataract surgery.

PURPOSE: To investigate whether multifocal electroretinogram (mfERG) topography would be affected by nuclear cataract. METHODS: Multifocal electroretinograms were recorded from 10 elderly subjects (10 eyes) with nuclear cataract of grade five (LOCS III) before and after cataract surgery (phacoemulsification). Their visual acuity before the cataract surgery was between 6/12 and 6/18. The postoperative period was from 2 to 3 months. None of the subjects had any significant eye disease apart from cataract. The mfERG responses were grouped into six concentric rings for analysis. Both the amplitudes and the latencies of N1 and P1 of first-order responses were used for analysis. RESULTS: N1 amplitude only from ring 1 increased significantly after cataract surgery. P1 amplitude from ring 1 and ring 2 also increased significantly after cataract surgery. The latencies of neither N1 nor P1 from all rings changed significantly. CONCLUSIONS: Nuclear cataract could affect the topography of mfERG, so clinicians should be aware of the effects of cataract when interpreting mfERG responses in cataract patients.

Effects of ion transport and channel-blocking drugs on aqueous humor formation in isolated bovine eye.

PURPOSE: To investigate the role of active chloride secretion by the ciliary epithelium in the formation of aqueous humor (AH), by using the in vitro perfused eye. METHODS: Bovine eyes collected from an abattoir were cannulated through the ophthalmic artery and perfused with oxygenated Krebs' solution at 37 degrees C. Aqueous humor formation (AHF) was measured by the fluorescein-dilution technique. Drugs were added to the perfusate and/or to the anterior chamber. RESULTS: NaK-adenosine triphosphatase (ATPase) inhibitor, ouabain (1.0 mM), produced a significant reduction in AHF by 46% and 42% when added to the stromal or aqueous side, respectively. When added to both sides (1.0 mM), it produced a reduction of 61%. Bumetanide (0.1 mM), a specific inhibitor of Na-K-2Cl cotransport, and furosemide (0.1 mM), a nonspecific anion transport inhibitor, produced 35% and 45% reductions when applied to the stromal side. DIDS (0.001-0.1 mM), which is believed to inhibit the Cl-HCO(3) exchanger, Na-HCO(3) cotransporter, and chloride channel, produced a dose-dependent reduction when added to the stromal side. The inhibition was 55% by the highest concentration used. 5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB; 0.1 mM), a chloride channel blocker in the nonpigmented cells, produced a 25% reduction when applied to the aqueous side. Acetazolamide (0.1 mM), a carbonic anhydrase inhibitor, applied to the stromal side, produced 31% reduction. CONCLUSIONS: At least 60% of the AH is formed by active secretion in bovine eyes. Transport of anions through the ciliary epithelium (CE), particularly the chloride ion, plays a crucial role in AHF.