Andean drought and glacial retreat tied to Greenland warming during the last glacial period.

Abrupt warming events recorded in Greenland ice cores known as Dansgaard-Oeschger (DO) interstadials are linked to changes in tropical circulation during the last glacial cycle. Corresponding variations in South American summer monsoon (SASM) strength are documented, most commonly, in isotopic records from speleothems, but less is known about how these changes affected precipitation and Andean glacier mass balance. Here we present a sediment record spanning the last ~50 ka from Lake Junín (Peru) in the tropical Andes that has sufficient chronologic precision to document abrupt climatic events on a centennial-millennial time scale. DO events involved the near-complete disappearance of glaciers below 4700 masl in the eastern Andean cordillera and major reductions in the level of Peru's second largest lake. Our results reveal the magnitude of the hydroclimatic disruptions in the highest reaches of the Amazon Basin that were caused by a weakening of the SASM during abrupt arctic warming. Accentuated warming in the Arctic could lead to significant reductions in the precipitation-evaporation balance of the southern tropical Andes with deleterious effects on this densely populated region of South America.

Longitudinal expression profiling of CD4+ and CD8+ cells in patients with active to quiescent giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) is the most common form of vasculitis affecting elderly people. It is one of the few true ophthalmic emergencies but symptoms and signs are variable thereby making it a challenging disease to diagnose. A temporal artery biopsy is the gold standard to confirm GCA, but there are currently no specific biochemical markers to aid diagnosis. We aimed to identify a less invasive method to confirm the diagnosis of GCA, as well as to ascertain clinically relevant predictive biomarkers by studying the transcriptome of purified peripheral CD4+ and CD8+ T lymphocytes in patients with GCA. METHODS: We recruited 16 patients with histological evidence of GCA at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and aimed to collect blood samples at six time points: acute phase, 2-3 weeks, 6-8 weeks, 3 months, 6 months and 12 months after clinical diagnosis. CD4+ and CD8+ T-cells were positively selected at each time point through magnetic-assisted cell sorting. RNA was extracted from all 195 collected samples for subsequent RNA sequencing. The expression profiles of patients were compared to those of 16 age-matched controls. RESULTS: Over the 12-month study period, polynomial modelling analyses identified 179 and 4 statistically significant transcripts with altered expression profiles (FDR < 0.05) between cases and controls in CD4+ and CD8+ populations, respectively. In CD8+ cells, two transcripts remained differentially expressed after 12 months; SGTB, associated with neuronal apoptosis, and FCGR3A, associatied with Takayasu arteritis. We detected genes that correlate with both symptoms and biochemical markers used for predicting long-term prognosis. 15 genes were shared across 3 phenotypes in CD4 and 16 across CD8 cells. In CD8, IL32 was common to 5 phenotypes including Polymyalgia Rheumatica, bilateral blindness and death within 12 months. CONCLUSIONS: This is the first longitudinal gene expression study undertaken to identify robust transcriptomic biomarkers of GCA. Our results show cell type-specific transcript expression profiles, novel gene-phenotype associations, and uncover important biological pathways for this disease. In the acute phase, the gene-phenotype relationships we have identified could provide insight to potential disease severity and as such guide in initiating appropriate patient management.

Participant understanding and recall of informed consent for induced pluripotent stem cell biobanking.

The ability to generate human induced pluripotent stem cells (iPSCs) has opened new avenues for human disease modelling and therapy. The aim of our study was to determine research participants' understanding of the information given when donating skin biopsies for the generation of patient-specific iPSCs. A customised 35-item questionnaire based on previous iPSC consent guidelines was sent to participants who had previously donated samples for iPSC research. The questionnaire asked pertinent demographic details, participants' motivation to take part in iPSC research and their attitudes towards related ethical issues. 234 participants were contacted with 141 (60.3 %) complete responses received. The median duration between recruitment and follow-up questioning was 313 days (range 10-573 days). The majority of participants (n = 129, 91.5 %) believed they understood what a stem cell was; however, only 22 (16.1 %) correctly answered questions related to basic stem cell properties. We found no statistically significant difference in responses from participants with different levels of education, or those with a health sciences background. The poor understanding amongst participants of iPSC research is unlikely to be unique to our study and may impact future research if not improved. As such, there is a need to develop an easily understood yet comprehensive consent process to ensure ongoing ethical progress of iPSC biobanking.

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 (ß = -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.

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 µm. 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.

The incidence of neovascular subtypes in newly diagnosed neovascular age-related macular degeneration.

PURPOSE: To determine the frequency of neovascularization subtypes as determined by fluorescein angiography (FA) alone vs FA and optical coherence tomography (OCT) grading in age-related macular degeneration (AMD). DESIGN: Retrospective cohort. METHODS: participants: Newly diagnosed neovascular AMD patients who initiated intravitreal anti-vascular endothelial growth factor therapy by 1 physician from October 1, 2005 to December 1, 2012. interventions: Two independent graders classified the baseline lesions using FA alone and FA+OCT. main outcome measures: Analysis of the frequency of lesion subtypes by FA alone or FA+OCT and agreement between both classification systems was performed. RESULTS: A total of 232 patients (266 eyes) fit the inclusion criteria. Mean age was 86.3 years; 67.7% of eyes (180/266) were from female patients, and 95.5% (254/266) were from white patients. The distribution using FA alone was 49.6% (132/266), 12.0% (32/266), 28.6% (76/266), and 9.8% (26/266) among occult, classic, retinal angiomatous proliferation, and mixed choroidal neovascularization, respectively. With FA+OCT, 39.9% (106/266), 9.0% (24/266), 34.2% (91/266), and 16.9% (45/266) were type 1 (sub-retinal pigment epithelium), type 2 (subretinal), type 3 (intraretinal), and mixed neovascularization (NV), respectively. The κ statistic was 0.65 (standard error ±0.37, P < .001) between the 2 classification systems, representing good agreement. CONCLUSION: With both FA-alone and FA+OCT grading, we found a higher incidence of type 3 NV in eyes with newly diagnosed neovascular AMD than that reported in prior studies. The κ statistic between the 2 classification systems showed "good" agreement. The discrepancies are likely attributable to the identification of a higher frequency of type 3 and mixed NV and a lower frequency of type 1 NV with the aid of OCT.

Better ventilator settings using a computerized clinical tool.

BACKGROUND: The Acute Respiratory Distress Syndome (ARDS) Network low tidal volume (VT) trial paved the ground for mechanically ventilating ARDS patients with a VT of 6 mL/kg ideal body weight (IBW). Although there is no consensus that a low VT is advantageous in non-ARDS patients,it is accepted that high VT should be avoided. Because compliance rates with ventilator recommendations are 30%, there is a need for process improvement. We postulated that a computerized screen prompt that recommended VT based on height would improve compliance with low VT.During ventilator order entry, the computerized decision tool prompts the clinician and encourages ventilation of patients at 8 mL/kg IBW, and 6 mL/kg IBW for patients with ARDS. METHODS: A retrospective review was performed on patients who required volume controlled mechanical ventilation over a 3-y period. Subjects were chosen randomly from the respiratory records of 6 different ICUs at a single tertiary care academic center. Half of the charts selected were before intervention of on-screen prompt, and the other half were after implementation of the computerized decision tool. RESULTS: The initial set VT ranged from 6.26 to 13.45 mL/kg IBW, with a mean of 8.92 mL/kg. After implementation of the on-screen prompt, mean VT decreased by 0.84 mL/kg to 8.07 mL/kg (P= .001) with a lower range of 4.73-11.56 mL/kg IBW. We also noted a significant decrease in the number of subjects placed on an initial VT > 10 mL/kg IBW from 20% to 4% (P= .003). CONCLUSIONS: A computerized clinical decision tool with the preferred initial VT settings based on the patients' sex and height is a safe and reliable way to increase low VT strategy compliance across multiple ICUs. Its limitations are similar to those shared by other computer-generated prompts.

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 +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.

Structural and functional analysis of the globular head domain of p115 provides insight into membrane tethering.

Molecular tethers have a central role in the organization of the complex membrane architecture of eukaryotic cells. p115 is a ubiquitous, essential tether involved in vesicle transport and the structural organization of the exocytic pathway. We describe two crystal structures of the N-terminal domain of p115 at 2.0 A resolution. The p115 structures show a novel alpha-solenoid architecture constructed of 12 armadillo-like, tether-repeat, alpha-helical tripod motifs. We find that the H1 TR binds the Rab1 GTPase involved in endoplasmic reticulum to Golgi transport. Mutation of the H1 motif results in the dominant negative inhibition of endoplasmic reticulum to Golgi trafficking. We propose that the H1 helical tripod contributes to the assembly of Rab-dependent complexes responsible for the tether and SNARE-dependent fusion of membranes.

Fine mapping linkage analysis identifies a novel susceptibility locus for myopia on chromosome 2q37 adjacent to but not overlapping MYP12.

PURPOSE: Myopia (shortsightedness) is one of the most common ocular conditions worldwide and results in blurred distance vision. It is a complex trait influenced by both genetic and environmental factors. We have previously reported linkage of myopia to a 13.01 cM region of chromosome 2q37 in three large multigenerational Australian families that initially overlapped with the known myopia locus, MYP12. The purpose of this study was to perform fine mapping of this region and identify single nucleotide polymorphisms (SNPs) associated with myopia. METHODS: Fine mapping linkage analysis was performed on three multigenerational families with common myopia to refine the previously mapped critical interval. SNPs in the region were also genotyped to assess for association with myopia using an independent case-control cohort. RESULTS: The disease interval was refined to a 1.83 cM region that is adjacent to rather than overlapping with the MYP12 locus. Subsequent sequencing of all known and hypothetical genes as well as an association study using an independent myopia case-control cohort showed suggestive but not statistically significant association to two intronic SNPs. CONCLUSIONS: We have identified a novel locus for common myopia on chromosome 2q37.

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.

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.

Genetic dissection of myopia: evidence for linkage of ocular axial length to chromosome 5q.

PURPOSE: To estimate heritability and locate quantitative trait loci influencing axial length. DESIGN: Classic twin study of monozygotic and dizygotic twins reared together. PARTICIPANTS: Eight hundred ninety-three individuals from 460 families were recruited through the Twin Eye Study in Tasmania and the Brisbane Adolescent Twin Study (BATS) and had ocular axial length measured. METHODS: Structural equation modeling on the entire sample was used to estimate genetic and environmental components of variation in axial length. Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 individuals from 142 BATS families. MAIN OUTCOME MEASURE: Ocular axial length. RESULTS: The heritability estimate for axial length, adjusted for age and sex, in the full sample was 0.81. The highest multipoint logarithm of the odds (LOD) score observed was 3.40 (genomewide P = 0.0004), on chromosome 5q (at 98 centimorgans [cM]). Additional regions with suggestive multipoint LOD scores were also identified on chromosome 6 (LOD scores, 2.13 at 76 cM and 2.05 at 83 cM), chromosome 10 (LOD score, 2.03 at 131 cM), and chromosome 14 (LOD score, 2.84 at 97 cM). CONCLUSION: Axial length, a major endophenotype for refractive error, is highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.

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.

Linkage replication of the MYP12 locus in common myopia.

PURPOSE: Myopia is a common disorder with a large public health impact. Although 12 myopia loci have been reported and heterogeneity for high myopia loci have been demonstrated, replication of high-myopia loci with a common myopia phenotype has not been successful. This study reports the successful replication of MYP12 in three large, multigenerational families with autosomal dominant (AD) common myopia (spherical equivalent [SphE]

Evaluation of accuracy in proband-reported family history and its determinants: the Genes in Myopia family study.

PURPOSE: Proband-reported family histories are widely used in epidemiological and genetic studies. The accuracy of these reports may have significant effects on the intended outcome, particularly in genetic studies. This study aims to determine the accuracy of proband-reported family history of myopia and to assess whether demographic or clinical factors are predictive of an accurate history. METHODS: In 2004 to 2005, the study recruited 120 myopic probands (< or = -0.50 D spherical equivalent in both eyes) aged 18 to 72 years and 358 nuclear family members residing within Victoria, Australia as part of the Genes in Myopia (GEM) family study. Data collection used an examiner-administered questionnaire with an ocular examination. Proband-reported family history of myopia was evaluated for agreement with ophthalmic examination results of family members. RESULTS: The statistical measures of accuracy used in this report were sensitivity, specificity, positive predictive value, and negative predictive value. Sensitivity varied from 85 to 98%, specificity from 84 to 96%, positive predictive value from 83 to 97%, and negative predictive value from 84 to 97%. Following multivariate analysis, an evaluation of demographic and clinical factors indicated that the highest predictive accuracy was obtained from proband reporting of their children [odds ratio (OR), 0.38; 95% confidence interval (CI), 0.15 to 0.94] whereas the most inaccurate reporting of a proband was when there was less-severe maternal myopia (per 0.50 D less myopic) (OR, 1.23; 95% CI, 1.06 to 1.43) or for increase in total education of the proband (per 1 year increase) (OR, 1.22; 95% CI, 1.04 to 1.42). CONCLUSIONS: Several variables influence the accuracy of obtaining a family history of myopia. A questionnaire-based approach alone will introduce some error into the study and this should be taken into account when designing and undertaking family-based epidemiological or genetic studies of myopia.

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, > or = 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.