Matthew Chamberlain

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.

Gene-environment interactions and aging visual function: a classical twin study.

OBJECTIVE To elucidate the contribution of environmental versus genetic factors to the significant losses in visual function associated with normal aging. DESIGN A classical twin study. PARTICIPANTS Forty-two twin pairs (21 monozygotic and 21 dizygotic; age 57-75 years) with normal visual acuity recruited through the Australian Twin Registry. METHODS Cone function was evaluated by establishing absolute cone contrast thresholds to flicker (4 and 14 Hz) and isoluminant red and blue colors under steady state adaptation. Adaptation dynamics were determined for both cones and rods. Bootstrap resampling was used to return robust intrapair correlations for each parameter. MAIN OUTCOME MEASURES Psychophysical thresholds and adaptational time constants. RESULTS The intrapair correlations for all color and flicker thresholds, as well as cone absolute threshold, were significantly higher in monozygotic compared with dizygotic twin pairs (P<0.05). Rod absolute thresholds (P = 0.28) and rod and cone recovery rate (P = 0.83; P = 0.79, respectively) did not show significant differences between monozygotic and dizygotic twins in their intrapair correlations, indicating that steady-state cone thresholds and flicker thresholds have a marked genetic contribution, in contrast with rod thresholds and adaptive processes, which are influenced more by environmental factors over a lifetime. CONCLUSIONS Genes and the environment contribute differently to important neuronal processes in the retina and the role they may play in the decline in visual function as we age. Consequently, retinal structures involved in rod thresholds and adaptive processes may be responsive to appropriate environmental manipulation. Because the functions tested are commonly impaired in the early stages of age-related macular degeneration, which is known to have a multifactorial etiology, this study supports the view that pathogenic pathways early in the disease may be altered by appropriate environmental intervention. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Testing Protocol and Recruitment in the Genes in Myopia Twin Study

Purpose: The genes in myopia twin study were established to assess the relative genetic contribution of spherical equivalent using a classical twin model. This manuscript will provide a detailed outline of the methodological design, twin recruitment, and the prevalence of myopia in the genes in myopia twin study. Methods: All Victorian-based twins registered with the Australian Twin Registry aged 18 years or older were invited to participate genes in myopia twin study. Each subject underwent a general questionnaire, comprehensive eye examination, and a blood sample was collected. Myopia was defined as worse than or equal to −0.50 diopters sphere (in at least one eye). Results: A total of 627 twin pairs out of 4,158 twin pairs consented to participate in the genes in myopia twin study. A total of 345 monozygotic and 267 dizygotic twin pairs aged between 18 and 86 years were examined. The response rate for monozygotic twins (19.8%) was almost double that of dizygotic twins (11.7%). The overall prevalence of myopia was 29.7% for all twins. Conclusions: The genes in myopia twin study is the first Australian-based twin study to assess refraction in an adult twin population and the largest of its kind in the world. The comprehensive testing protocol used in the in the genes in myopia twin study has provided an extensive twin database for genetic analysis. Participation rate was found to vary according to zygosity, gender, and age.

Heritability of the spatial distribution and peak density of macular pigment: a classical twin study

PurposeTo elucidate the heritability of peak density and spatial width of macular pigment (MP) using a Classical Twin Study.MethodsFundus autofluorescence images were obtained at 488 nm from 86 subjects or 43 twin pairs (21 monozygotic (MZ) and 22 dizygotic (DZ)) (27 male, 59 female) aged from 55 to 76 years (mean 62.2±5.3 years). The relative topographic distribution of MP was measured using a grey scale of intensity (0–255 units) in a 7° eccentricity around the fovea. Relative peak MP density (rPMPD) and relative spatial distribution of MP (rSDMP) were used as the main outcome measure in the statistical analysis.ResultsA significantly higher correlation was found within MZ pairs as compared with that within DZ pairs for rPMPD, (r=0.99, 95% confidence interval (95% CI) 0.93 to 1.00) and 0.22, 95% CI −0.34 to 0.71), respectively, suggesting strong heritability of this trait. When rSDMP was compared, there was no significant difference between the correlations within MZ pairs (r=0.48, 95% CI −0.02 to 0.83) and DZ pairs (r=0.63, 95% CI 0.32 to 0.83), thus rSDMP is unlikely to have a considerable heritable component. In addition, there was no difference between any MP parameter when normal maculae were compared with early age-related macular degeneration (AMD) (rPMPD 0.36 vs 0.34, t=1.18 P=0.243, rSDMP 1.75 vs 1.75, t=0.028 P=0.977).ConclusionsrPMPD is a strongly heritable trait whereas rSDMP has minimal genetic influence and a greater influence by environmental factors. The presence of macular changes associated with early AMD did not appear to influence any of these pigment parameters.

Role of Genetic Factors in Lower- and Higher-Order Aberrations – The Genes in Myopia Twin Study

Aims: We intended to investigate the relative genetic contribution in wavefront aberrations using a sub-group of twins recruited in the Genes in Myopia twin study, and subsequently provide direction for future studies into the aetiology of mono-chromatic aberrations. To our knowledge, the Genes in Myopia twin study is the first study to explore the role of genetic factors in both lower- and higher-order aberrations in a Caucasian population. Methods: Each individual completed a general questionnaire and underwent a comprehensive eye examination. Higher-order wavefront aberrations were calculated with Zernike coefficients up to the fourth order. Results: A total of 46 twin pairs with a mean age of 65.3 years were included in the analysis. Monozygotic intra-pair correlations were significantly higher compared to those in dizygotic twin pairs for defocus aberrations (p < 0.05). A trend for a genetic component was identified for higher-order aberrations. Conclusion: Genetic studies into refraction typically explore the genetic effects of lower-order aberrations such as myopia and hypermetropia; however, there is little to no research into the genetic basis of higher-order aberrations. The Genes in Myopia twin study indicates a potential genetic role for higher-order aberrations and provides useful insights into the aetiology of refractive error.

Marked discordance for myopia in female monozygotic twins

Female monozygotic twins aged 54 years discordant for myopia are reported. One twin presented with bilateral high myopia (right eye = −6.00/+0.50 × 5°, left eye = −6.00/+0.50 × 45°) and her identical twin had no significant refractive error (right eye = −0.50/plano, left eye = −0.50/+0.75 × 40°). An explanation for the striking refractive discordance seen in this case report is yet to be determined.

Concordant bilateral Duane's Retraction Syndrome (type 1) in female monozygotic twins.

We report a single case study of concordant bilateral Duane’s Retraction Syndrome (DRS) (type 1) in female monozygotic (MZ) twins aged 47 years. The twin pair were recruited through the Australian Twin Registry as part of a twin study on myopia. This twin pair were full term and had a similar birth weight: 2.27 kg and 1.81 kg in twin 1 and twin 2, respectively. There was no report of any other childhood medical conditions in either twin. Both twins had an equal amount of restriction in right and left abduction. Narrowing of the palpebral fissures and globe retraction in right and left adduction was also observed in both twins. To our knowledge this is the first case to report concordant bilateral DRS (type 1) in female MZ twins. The concordance for the presence of DRS and associated clinical signs observed in this MZ twin pair supports a genetic origin to DRS.