Christine Y. Chen

Management of submacular hemorrhage with intravitreal injection of tissue plasminogen activator and expansile gas.

Purpose: To evaluate the clinical outcome of intravitreal tissue plasminogen activator (tPA) and expansile gas injection as a minimally invasive treatment for submacular hemorrhage (SMH). Methods: This study was a retrospective clinical case series examining 104 eyes that received an intravitreal injection of 30–100 mcg of tPA and expansile gas (SF6 or C3F8) for SMH. The main outcomes evaluated were visual acuities (VA), anatomic displacement of submacular blood, and surgical complications. Results: A total of 85, 77, and 81 eyes were available at 1 week, 3 months, and 12 months follow up, respectively. Postoperatively, ≥2 Snellen lines improvement were achieved in 43/85 eyes (51%) at 1 week, 49/77 eyes (63%) at 3 months, and 52/81 eyes (64%) at 12 months. Postoperative VA improvement was significantly associated with preoperative VA, submacular blood displacement, and the underlying cause of SMH. Diagnostic postoperative angiogram and clinical examination were possible at 8.2 ± 7.4 weeks and 9.5 ± 7.4 weeks, respectively. The observed complications included breakthrough vitreous hemorrhage in 8 eyes (8%) and retinal detachment in 3 eyes (3%). Conclusions: In this retrospective series, intravitreal injection of tPA and expansile gas was shown to be a safe and effective technique that can improve VA in most eyes with SMH and assist in the diagnosis of the underlying cause.

Refractive errors in twin studies.

It is estimated that 1.6 billion people worldwide have myopia, a refractive error, and this number is expected to increase to approximately 2.5 billion by the year 2020. It is now well established that both the environment and genetics play a role in the development of myopia. However, the exact contribution of each of these components to myopia development has yet to be completely determined. Twin studies (classical twin model) are commonly used to determine the weighting of genetic and environmental components in disease. Over the last century, twin studies have investigated the heritability of refractive errors in different sample populations and have collectively supported a genetic basis to refractive errors. However, different sample populations and methods of data collection have produced a wide range of heritability estimates ranging from .5 to .9. This article will review those twin studies that have investigated refractive error, particularly myopia, as well as biometric measures linked to refractive error, to compare heritability estimates and methodology designs.

Role of the hepatocyte growth factor gene in refractive error.

OBJECTIVE Refractive errors such as myopia and hypermetropia are among the leading causes of visual impairment worldwide. Several genetic loci have been associated with myopia but none to date have been reported for hypermetropia. We investigated the hepatocyte growth factor (HGF) as a candidate gene influencing these 2 refractive error states. DESIGN Case-control study. PARTICIPANTS A total of 551 individuals (193 males, 358 females; mean age, 55.41+/-12.65 years) including 117 individuals with high myopia <or= -6.00 diopters (D), 140 individuals with low/moderate myopia (-2.00 to -5.99 D), 148 emmetropic individuals (-0.50 to +0.75 D) and 146 hyperopic individuals (>+2.00 D) were included in the analysis from 3 different Australian population cohorts (The Genes in Myopia Study, the Blue Mountains Eye Study, and the Melbourne Visual impairment project). METHODS Genotyping of 9 tag single nucleotide polymorphisms (SNPs) that encompassed the entire HGF gene and its associated sequences as well as 6 additional SNPs identified through DNA resequencing was undertaken. MAIN OUTCOME MEASURES Genetic association with refraction. RESULTS After correction for multiple testing, the SNPs rs12536657 (odds ratio [OR], 5.53; 95% confidence interval [CI], 1.14-26.76) and rs5745718 (OR, 2.24; 95% CI, 1.30-3.85) showed significant association with hypermetropia. Whereas the SNPs rs1743 (OR, 2.02; 95% CI, 1.19-3.43; P = .009), rs4732402 (OR, 2.03; 95% CI, 1.23-3.36; P = 0.005), rs12536657 (OR, 2.38; 95% CI, 1.40-4.05; P = 0.001), rs10272030 (OR, 2.22; 95% CI, 1.31-3.75; P = 0.003), and rs9642131 (OR, 2.44; 95% CI, 1.43-4.14; P = 0.001) showed significant association with low/moderate myopia. CONCLUSIONS These findings present the HGF gene as the first gene significantly associated with hypermetropia as well as providing evidence of significant association with myopia in a second ethnic population. In addition, it provides insights into the important biological mechanisms that regulate human ocular development (emmetropization), which are currently poorly understood.

Vision-related Quality of Life Comparison for Emmetropes, Myopes After Refractive Surgery, and Myopes Wearing Spectacles or Contact Lenses

PURPOSE To compare the vision-related quality of life among emmetropes, myopes who had refractive surgery, and myopes who wore spectacles and/or contact lenses. METHODS This cross-sectional study assessed vision-related quality of life using the Vision Quality of Life Index. Participants were age 18 years or older with a presenting visual acuity of 20/40 or better and no other ocular pathology. Responses were compared among three groups: emmetropes (spherical equivalent [SE] < 0.50 to > -0.50 diopters [D]), myopes (SE < or = -0.50 D) who wore spectacles and/or contact lenses, and myopes who had refractive surgery. RESULTS The study population included 64 emmetropes, 66 myopes who wore spectacles and/or contact lenses, and 65 myopes who had refractive surgery. No significant differences were found between the refractive surgery and emmetropic groups. In contrast, the spectacle and/or contact lens group had significantly increased odds of having concerns about injuring themselves (odds ratio = 11.5, 95% confidence interval [CI] 2.3, 57.1), difficulties coping with demands in life (odds ratio = 23.6, 95% CI 23.8, 198.1), difficulties fulfilling roles (odds ratio = 5.6, 95% CI 1.4, 22.1), and less confidence joining in everyday activities (odds ratio = 30.6, 95% CI 3.2, 292.3) compared to emmetropes. CONCLUSIONS Myopia corrected with spectacles or contact lenses had a negative impact on some areas of vision-related quality of life. However, individuals with myopia who had refractive surgery enjoyed the same vision-related quality of life as those with emmetropia. The potential improvement in vision-related quality of life should be considered when recommending treatment for myopia.

Assessment of TGIF as a candidate gene for myopia.

PURPOSE Transforming growth beta-induced factor (TGIF) has been identified as a candidate gene for high myopia through genetic linkage studies and through its role in ocular growth in animal studies. However, the association of single nucleotide polymorphisms (SNPs), based solely on myopia refraction, has so far been inconclusive. This is the first study conducted to investigate the association of TGIF with refraction and ocular biometric measurements. METHODS Twelve tag SNPs (tSNPs) encompassing the TGIF gene and 2 kb upstream of its promoter region were used to evaluate the association between TGIF variants with both ocular biometric measures and refraction. A total of 257 cases of myopia (spherical equivalent [SE] worse than -0.50 D) and 294 control subjects (no myopia) were genotyped. Genotype frequencies were analyzed by chi(2) test and one-way ANOVA. RESULTS Two tSNPs showed significant association with biometric measures, with the SNP rs8082866 being associated with both axial length (P = 0.013) and corneal curvature (P = 0.007) and the SNP rs2020436 being associated with corneal curvature (P = 0.022). However, these associations became nonsignificant after multiple testing (Bonferroni correction). CONCLUSIONS Findings of this study suggest that the TGIF gene is unlikely to play a major role in either ocular biometric measures or refraction in a Caucasian population. Future studies should focus on other genes in the MYP2 linkage region or other linked regions to identify myopia-causing genes.

Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1–6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4–13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

Methodology and recruitment of probands and their families for the Genes in Myopia (GEM) Study.

Purpose: Myopia is considered to be a complex disease involving both environmental and genetic factors. The Genes in Myopia (GEM) Study aims to recruit probands with myopia and their family members to allow genetic analysis of myopia to be undertaken. The purpose of this paper is to describe the methodology and recruitment of probands and families for the GEM Study. Methods: In a sample-based prospective study, 2,095 probands with myopia of −0.50 DS or worse and a positive family history of myopia were contacted via the Melbourne Excimer Laser Group (MELG) database. Probands and family members recruited into the study undertook a detailed assessment including questionnaire, best-corrected visual acuity, objective and subjective refraction, axial length, anterior chamber depth, keratometry readings, slit-lamp examination, height, weight and head circumference measurements, and blood sample collection for DNA analysis. Results: 280 probands with myopia have been recruited into the GEM Study. Probands had a mean age of 49.33 yrs. (SD +/− 11.64) with the average age of myopia onset being 12.58 years (SD +/− 6.71). The average spherical-component refractive error was: right eye −5.13 DS (SD +/− 3.06) and left eye −5.14 DS (SD +/− 3.16). Probands with extreme myopia (−10 DS or worse) showed the highest study participation rate of 56%, when compared to high (−5 DS < −10 DS) (20%), moderate (−3 DS < − 5 DS) (18%) and low myopia (−0.5 DS < −3 DS) (10%). A total of 279 out of 505 (55%) additional family members recruited were also found to be myopic. Conclusions: The GEM study has used a targeted approach to identify an Australian cohort with a diverse spread of myopia, ranging from low to extreme. Recruitment of probands via the use of an excimer laser practice has proved to be an efficient and economic means of identifying probands with a family history of myopia. In addition, the participation rate in the study appears to vary reflecting a probands perception of disease severity.

Correlation between neovascular lesion type and clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration.

Purpose: To investigate the association between the type of neovascularization (NV) and the clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration. Methods: Eighty-three patients with treatment-naive, unilateral, neovascular age-related macular degeneration were retrospectively analyzed. Neovascular lesions were classified using both fluorescein angiography and optical coherence tomography as Type 1 (subretinal pigment epithelium), 2 (subretinal), 3 (intraretinal), or mixed NV. The associations between NV lesion type and baseline clinical and imaging characteristics of the fellow eye, including central geographic atrophy, noncentral geographic atrophy, pigmentary changes, soft drusen, cuticular drusen, reticular pseudodrusen, and subfoveal choroidal thickness, were examined. Subfoveal choroidal thickness was defined as thin if thickness was <120 &mgr;m. Results: In the fellow eyes of patients with treatment-naive, unilateral, neovascular age-related macular degeneration, Type 3 NV had an increased adjusted odds ratio of reticular pseudodrusen (15.361, P < 0.001) and thin subfoveal choroidal thickness (21.537, P < 0.001) as well as a tendency toward an increased adjusted odds ratio of central geographic atrophy (4.775, P = 0.028). Fellow eyes of patients with Type 1 NV showed a decreased adjusted odds ratio of reticular pseudodrusen (0.233, P = 0.007) and thin subfoveal choroidal thickness (0.080, P = 0.005). Conclusion: In patients with unilateral, neovascular age-related macular degeneration, certain nonneovascular features of the fellow eye correlate with the NV lesion composition based on type, as anatomically classified utilizing both fluorescein angiography and optical coherence tomography. Patients with Type 3 NV were more likely to have reticular pseudodrusen and/or thin subfoveal choroidal thickness in the fellow eye compared with those with Type 1 NV. Patients with Type 3 NV also showed a trend toward increased central geographic atrophy in the fellow eye.

Baseline Predictors for Good Versus Poor Visual Outcomes in the Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Therapy.

PURPOSE To examine the baseline factors associated with good (20/60 or better) versus poor (20/200 or worse) visual outcomes in eyes with treatment-naïve neovascular age-related macular degeneration (AMD) receiving intravitreal antivascular endothelial growth factor (VEGF) on a treat-and-extend regimen (TER). METHODS An observational, retrospective series of patients managed with a TER, identified as having either good or poor visual outcomes, was examined. A multivariate regression analysis of baseline characteristics identified factors associated with good and poor vision at 2, 3, and 4 years. Neovascular subtypes were identified using fluorescein angiography (FA) alone and the anatomic classification system with FA and optical coherence tomography (OCT). RESULTS One hundred thirty-eight patients (154 eyes) fit the inclusion criteria at 2 years, 106 patients (113 eyes) at 3 years, and 72 patients (74 eyes) at 4 years. In the multivariate analysis, type 1 lesions, according to anatomic classification, had better vision at 24 months (95% CI: [3.1, 82.7], P = 0.01), 36 months (95% CI: [1.97, 24.17], P = 0.003), and 48 months (95% CI: [2.01, 65.47], P = 0.006). Clopidogrel use was associated with poor vision at 24 months (95% CI: [0.03, 0.68], P = 0.013). Vision at 3 months was the best predictor of vision at year 4 (β = -4.277, P = 0.002). CONCLUSIONS Eyes with neovascular AMD managed with a TER of anti-VEGF therapy having type 1 neovascularization at baseline were more likely to maintain good vision over 4 years, whereas clopidogrel use predicted poor vision at 2 years. Vision at 3 months was the best predictor for favorable long-term vision.

Myopia and Personality: The Genes in Myopia (GEM) Personality Study

PURPOSE A long-held view among the medical and broader community is that people who are short-sighted (myopic persons) have distinctive personality characteristics such as introversion and conscientiousness. However, existing research on this question is flawed, and its findings are inconsistent. The authors therefore aimed to determine whether myopia and personality are associated. METHODS The authors examined twins recruited through the Australian Twin Registry and a clinical-based family sample through a proband from a Melbourne Excimer Laser Clinic. There was no relation between family members and twins recruited in our study. Each individual underwent a full eye examination, completed a standard medical and general questionnaire, and was administered a five-factor model International Personality Item Pool (IPIP) inventory (Openness, Conscientiousness, Extroversion, Agreeableness, Neuroticism). Myopia was defined as worse than or equal to -0.50 (DS) spherical equivalent in the eye with the least refractive error. RESULTS Data from 633 individual twins aged 18 to 83 years (mean, 53.04 years) and 278 family members aged 11 to 90 years (mean, 49.84 years) were analyzed. Prevalence of myopia was 35.7% for twins and 47.6% for family members. Mean spherical equivalent was +0.13 DS (95% CI, +/-0.16) for twins and -1.13 DS (95% CI, +/-0.25) for family members. Correlation and regression results for personality for both sample cohorts after multivariate analysis did not support the view that myopic persons are introverted or conscientious; however, there was a significant but small association between myopia and Agreeableness (r = 0.08, P < 0.05). In multivariate analysis with age, sex, education, and the five personality factors entered as predictors, Openness was the only significant personality predictor of myopia in both samples. CONCLUSIONS This is the first multivariate study to assess links between personality and myopia using the IPIP. The long-held view that myopic persons are introverted and conscientious may reflect intelligence-related stereotypes rather than real correlations. Furthermore, the predictive characteristic of intellect, subsumed in Openness, appeared to be representative of a previously reported link between intellective abilities (IQ) and myopia rather than personality and myopia.