PolyU IR Collection: SO Theses

Retinal electrophysiological characteristics of the myopic eye

Sun, 01 Jan 2012 00:00:00 GMT

Title: Retinal electrophysiological characteristics of the myopic eye

Authors: Ho, Wing Cheung

Abstract: Introduction: Myopia is a common refractive error in the Chinese population. About 50% of the children in Hong Kong are myopic. Anatomically, myopia is usually characterized by an increase in axial length of the eyeball, leading to an optical focus in front of the retina. Although myopia can be simply corrected by optical aids to solve the vision problem, the elongated eyeball has been found to influence the retinal structure and physiology. Clinically, high myopes are at greater risk of developing retino-choroidal degeneration. Numerous studies have demonstrated reduced and delayed multifocal electroretinogram (mfERG) response in myopic adults. About 40% delayed mfERG response in myopic adults has been attributed to the effect of both refractive error and axial length, and the remaining variance of implicit time has been proposed to be related to attenuation of inner retinal function. In contrast, the mfERG response in myopic children is only delayed without significant change in amplitude. The reasons of underlying difference in retinal function between children and adults with myopia are still not clear. It has been shown that the retina can detect defocus signals locally in chicks. Inducing optical defocus in different retinal regions has profound effects on the compensatory response of the whole globe. However, there is still a lack of knowledge on the regional retinal activity in the presence of positive and negative optical defocus. In this study, we aimed to investigate the retinal function in myopic eyes of both children and young adults. In addition, we also studied the changes of retinal activity to the defocus signals in different regions. Objective: 1. To investigate the changes in adaptive circuitry of the inner retina in myopic adults by using the global flash mfERG at different contrast levels (Experiment 1). 2. To compare the retinal functions of myopic children versus young adults using global flash mfERG (Experiment 2). 3. To examine the retinal electrophysiological changes during myopia progression over a 1-year period in children (Experiment 3). 4. To study the effect of positive and negative optical defocus on changes of electrical response as a function of retinal region in adults (Experiment 4).; Methods: The mfERG measured with conventional stimulation mainly reflects the activity of the outer retina. The global flash mfERG, which incorporates the global flash screen response within conventional stimulation, can enhance inner retinal activity, in addition to outer retinal activity. So, this special paradigm of mfERG recording was used in this study. There are two components, the direct component (DC) and the induced component (IC), which reflect the activity from outer retina and inner retina respectively, recorded in the global flash mfERG paradigm. In Experiment 1, fifty-four adults (aged from 19 to 29 years) with various magnitudes of refractive error received the global flash mfERG at different levels of contrast, i.e. 29%, 49%, 65% and 96%. Cycloplegic subjective refraction and axial length were measured. Hierarchical multiple regression models were used to evaluate the effect of refractive error and the combined effects of refractive error and axial length on the mfERG responses. In Experiment 2, fifty-two children (aged from 9 to 14 years) and nineteen young adults (aged from 21 to 28 years) with refractive errors ranging from plano to -5.50 D were recruited for the global flash mfERG at both 49% and 96% contrasts. Refraction and axial length were measured. The analyses were the same as for Experiment 1. In Experiment 3, twenty-six children (aged from 9 to 13 years) received the global flash mfERG at both 49% and 96% contrasts and refraction in two visits 1-year apart. Pearson{174}s correlation was used to study the association between change in refraction and change in mfERG response in different retinal regions over the 1-year period. In Experiment 4, twenty-three subjects (aged from 19 to 25 years) with normal ocular health were recruited for global flash mfERG measures at 96% contrast under the condition of control (in-focus), positive defocus (+2 D and +4 D) and negative defocus (-2 D and -4 D) conditions. Repeated-measures ANOVA was used to investigate the effect of defocus on the mfERG response in different retinal regions. Results: In Experiment 1, myopic adults had a significant reduction in the paracentral DC amplitudes for both 29% and 49% contrasts and in the paracentral IC amplitudes at all contrasts measured. The peripheral IC amplitudes for 49% contrast were also reduced. Refractive error explained about 14% and 16% of the reduction in paracentral DC and IC amplitudes respectively, but axial length could not account for further change in either paracentral DC or IC amplitude in the hierarchical regression models used. Neither refractive error nor axial length contributed to any change in implicit time for either DC or IC response. In Experiment 2, myopic children had a significant reduction in central DC amplitude at 96% contrast and unaffected IC responses at both contrasts for all regions. In contrast, myopic adults showed a significant reduction in paracentral IC amplitudes at 49% contrast but not at 96% contrast. The DC amplitudes at both contrasts of all regions examined were virtually unaffected. Implicit times for DC and IC responses were unaffected for either group. In Experiment 3, children with progressing myopia showed significant reduction of central DC and IC amplitudes, and mild attenuation of paracentral DC and IC amplitudes at 49% contrast as myopia progressed. In Experiment 4, the mfERG responses were found to have more significant changes in the paracentral retinal region than in the central region under defocused conditions. The paracentral DC amplitudes showed a significant reduction under negative defocused conditions. In contrast, the paracentral IC amplitudes showed a significant increment under positive defocused conditions. Interestingly, the central IC response showed significant reduction in amplitude only to negative defocus, while the response increased in amplitude to positive defocus. However, the DC and IC implicit times were virtually unchanged under defocused conditions. Conclusions: This study shows that the effect of myopia mainly affected the inner retinal function in myopes. Retinal function was generally unaffected in myopic children, except for the outer retinal function in the central region. As myopia progressed, the inner retinal function from central to paracentral regions was reduced, especially in the central region. The retinal function in myopic adults differed from myopic children in terms of regions and retinal components being affected. The inner retinal function from paracentral to mid-peripheral regions was significantly impaired in myopic adults, whereas the outer retinal function in these regions was only mildly reduced due to myopia. There was also a progressive change of retinal impairment from central to mid-peripheral regions from children to adults with myopia. Moreover, paracentral retina in the human eye reacted more strongly to optical defocus than central retina did; paracentral retina also differentiated the sign of defocus. Therefore, we speculate that the regional deterioration in retinal function in adults with myopia is probably related to the effect of peripheral defocus on the myopic eye growth.

Description: xxiii, 199 leaves : ill. (some col.) ; 30 cm.; PolyU Library Call No.: [THS] LG51 .H577P SO 2012 Ho

Myopic related retinal changes among the Hong Kong Chinese high myopes

Sun, 01 Jan 2012 00:00:00 GMT

Title: Myopic related retinal changes among the Hong Kong Chinese high myopes

Authors: Cheng, Chi Kwan

Abstract: It has been often reported that sight threatening retinal complications are associated with high myopia more than -6 D in the adult population. High myopia is a leading cause of irreversible blindness, contributing around 6% to 13% of blindness as reported in previous worldwide studies. In cities like Hong Kong where the prevalence of myopia is in the range of 70% to 80%; myopia starts as early as the start of schooling and progresses steadily throughout the schooling age. Prevalence of high myopia presents a threat to the visual quality of this population. There was little information on the early changes in the retina, as well as the consequence of high myopia among schoolchildren and adolescents that would lead to retinal complications or other ocular pathologies. This study aims to indentify the early changes in the retina among school children and adolescents with high myopia and whether these retinal changes are any different from those of the adult population. This information may help to identify the possible risk factors including biometric and demographic characteristics for children or adolescents having high myopia ocular complications in their later years. In identifying an efficient and effective method in the detection of early retinal changes among the adolescent group, the latest available technology and instrumentation were explored. The Optomap was selected for the investigation of sensitivity and specificity in fundus screening. To further understand on how the retina changes in a myopic bigger eye, as a result of myopia progression and axial elongation, retinal thickness variation along the horizontal meridian was also investigated. This may shed lights on the relationship between anatomical variations and retinal complications. This study has three main objectives: 1. Identify an effective and efficient screening methodology 2. Determine the prevalence of retinal features for the 12 to 18 years high myopic adolescent and risk factors 3. Relate retinal thickness profile with the myopic retinal changes 1. Identify an effective and efficient screening methodology: To identify an efficient method in retinal screening / examination, the ultra wide field scanning laser ophthalmoscope was investigated. Fifty-four eyes identified with retinal / choroidal signs and eight normal eyes were recruited from 31 Hong Kong Chinese subjects to evaluate the use of Optomap on detecting retinal signs under non-mydriatic condition with standard procedure. Photodocumentation of fundal changes were taken by the Optomap under undilated conditions before a dilated fundus examination by a clinician. To combat the problem caused by the eyelid blocking the image, a cotton bud was used to retract the eyelid. Optomap images were evaluated by four other investigators for identifying retinal features under a masked condition. Results were compared with those obtained using a dilated fundus examination as the gold standard. The sensitivity and specificity of the Optomap averaged 76.4% and 71.9% respectively, which was similar to a previous report by other researchers. The fundal signs commonly missed by all observers were lattice degeneration (2 cases), white-without-pressure (1 case), paramacular drusen (1 case), and pigmentary change (1 case). Paramacular drusen were detected by contrasting the red laser channel and green laser channel, while other missed fundal signs were located in the far peripheral retina apparently outside the field of the Optomap. The Optos non-mydriatic fundus imaging system offers high sensitivity and specificity in fundus screening. Using a cotton bud to retract eyelid may be a useful modification especially for droopy eyelid patients. Optomap has certain advantages; however, there are limitations especially in some areas of the peripheral fundus may not be accessible. As a screening tool, the Optomap permits fundus examination without the use of a mydriatic agent, which is more comfortable for the patients, and that a permanent digital record of the findings can be kept. However, the colours of the Optomap are the artificial combination of two laser channels, resulting in a distorted image. Retinal lesions at the outside edges of the retina might not be detected. The Optomap is a complementary method to the standard dilated fundus examination but not as a substitute, especially with a high myopic population with a high risk of having retinal lesions.; 2. Determine the prevalence of retinal features for the 12 to 18 years high myopic adolescent and risk factors: To determine the prevalence and risk factors of myopic related retinal changes in young Hong Kong Chinese eyes with high myopia, 120 eyes were examined among school children with over -6 D myopia aged between 12 to 18 years. The eye with higher spherical equivalent error (SER) was used for analysis for each subject. Personal data collection, history related to myopia progression, biometry and documentation of retinal characteristics were performed with informed consent. Mean age of the subjects was 14.83 ± 1.58 years. Among the subjects, 50.8% were boys. The mean SER of the eyes was -8.41 ± 1.60 D. The five most frequent retinal lesions found were optic nerve crescents (52.5%), white-without-pressure (51.7%), lattice degeneration (5.8%) microcystoid degeneration (5%) and pigmentary degeneration (4.2%). Multiple logistic regressions showed axial length longer than 26.5 mm was a significant risk factor for peripheral lesions (p = 0.008, odd ratio 3.37), optic nerve crescents (p = 0.019, odd ratio 2.80) and white-without-pressure (p = 0.017, odd ratio 2.93). Peripheral retinal degenerative lesions and optic nerve crescent were found in a significant proportion of high myopic teenage subjects. There was a positive relationship between axial length and peripheral retinal lesions. There is a higher chance of having retinal lesions in eyes with axial length exceeding 26.5 mm in the age between 12 -18 years. Myopic related fundus changes could appear in early life in high myopic eyes. 3. Relate retinal thickness profile with the myopic retinal changes: The third study established the retinal thickness profiles in the central horizontal eighty degrees and relates retinal thickness profile with myopic retinal changes by comparing the profile between myopic and non-myopic eyes. The retinal thickness profiles of 30 myopic eyes (spherical equivalent error (SER) between -6.00 D and -13.63 D) and 31 non-myopic eyes (SER between +2.75 D and -0.50 D) were measured using the StratusOCT (Carl Zeiss Meditec, Dublin, CA). Two scan types were used: the Macular Thickness Map and the Customized Line Scan for a central 80 degrees horizontal retinal thickness profile. Myopic eyes have a thicker retina at the foveal center and fovea (p = 0.002 and 0.044 respectively), and thinner retina at other regions, compared to non-myopic eyes (p < 0.01, unpaired t-test). At other zones of the macula, the retina was significantly thinner in myopic eyes compared to non-myopic eyes (p < 0.01, unpaired t-test). From 40 degree nasal to 40 degree temporal retina, a general reduction of retinal thickness was observed across the myopic retina compared to the non-myopic retina, except at 20 degrees nasal to fixation. The peripheral retinal thickness was approximately 7% thinner in myopic eyes compared to the non-myopic eyes. General conclusions: Based on the results of the investigation with ultra wide field scanning laser ophthalmoscope, the Optos non-mydriatic fundus imaging system offers high sensitivity and specificity in fundus screening. The cotton bud eyelid retraction method may be a useful modification especially for droopy eyelid patients. However, there is still a chance that certain area of the fundus might not be identified. The Optomap is a complementary method to the standard dilated fundus examination but not a substitute, especially in a group with a high risk of retinal lesions, such as the high myopic population. The results of this prevalence study point out that myopic related fundus changes could appear in early life in high myopic eyes. There was a positive relationship between axial length and peripheral retinal lesions. There is a higher chance of having retinal lesions in eyes with axial length exceeding 26.5 mm in the age between 12 -18 years. As the myopic related retinal changes are present among this age group, though there are no urgent types of retinal lesion counted in our study, lesions like lattice degeneration is a predisposing factor of retinal detachment. Thus the early detection and assessment of fundal changes among young high myopes is important. An investigation of anatomatical retinal variation related to myopia, retinal thickness profiles have been established in the central horizontal eighty degrees in myopic and non-myopic eyes. This study found that myopic eyes have a thicker retina at the fovea and thinner retina at other regions compared to non-myopic eyes. From 40-degree nasal to 40-degree temporal retina, the peripheral retinal thickness was approximately 7% less in myopic eyes compared to the non-myopic eyes. We found retinal thickness reduction associates with high myopia in our study. There is a lot more to be done, such as correlating retinal changes with visual changes, and longitudinal monitoring to observe the changes over time.

Description: 227 leaves : ill. (some col.) ; 30 cm.; PolyU Library Call No.: [THS] LG51 .H577P SO 2012 Cheng

High Myopia partial reduction using orthokeratology (HM-PRO)

Sun, 01 Jan 2012 00:00:00 GMT

Title: High Myopia partial reduction using orthokeratology (HM-PRO)

Authors: Charm, Chi Foon Jessie

Abstract: PURPOSE: The High Myopia Partial Reduction Orthokeratology (HM-PRO) study was a 2-year, single-masked, randomized clinical study which assessed the clinical performance of partial reduction using orthokeratology (ortho-k) and myopic progression in high myopic children after two years of lens wear. METHODS: Children (8 to 11 years old) with spherical equivalent refraction 5.75D or above were recruited and randomly assigned into PR (partial reduction) ortho-k and control groups. PR ortho-k group used a custom made 4-zone ortho-k lenses (DreamLite, Procornea, The Netherlands) of target 4.00D to reduce the refractive errors. Residual refractive errors were corrected with a pair of glasses. Control subjects were fully corrected with single vision spectacles. Axial length (AL) was monitored with the IOLMaster during the treatment period. Complete ocular biometric data were collected at 6-month intervals. Analysis was performed on data from the right eye only. RESULTS: During the study, 79 children were screened, and 52 (66%) were eligible and enrolled. Half of the subjects were randomly assigned to PR ortho-k group and the other half to the control group. In PR ortho-k group, the median (range) myopic reduction and residual myopia were 3.75D (2.25D to 5.00D) and 2.75D (1.50D to 5.25D) respectively after 1-month lens wear. Residual refractive errors were corrected by a pair of spectacles and no significant difference was found in BCVA after stabilization of treatment at the 1-month visit. Pigmented arc was found in 32% of subjects after one month of lens wear. Observations of fluorescein staining of the cornea (less than Grade 2) were noted in some subjects at the 1-month visit. Twelve PR ortho-k and 16 control subjects completed this 2-year study. At the end of the study period, the median reduction in myopia was 4.50D (range: 2.75D to 6.25D) in the PR ortho-k group. Compared to the residual refractive errors at the 1-month visit (after lens stabilization), the median change in residual non-cycloplegic myopia at the 24-month visit was 0.13D (range: -0.75 to 1.00D). In the control group, the median increase in myopia was 1.00D (range: 0.50 to 2.50D). No significant change in astigmatism was observed in both groups. Corneal staining was observed in both groups of subjects at each visit but the frequency was generally higher in the PR ortho-k treated subjects At the end of the 2-year monitoring period, the mean±SD increases in AL were 0.19±0.21mm for the PR ortho-k group and 0.51±0.32mm for the control group (p=0.005). AL elongation was 63% slower in PR ortho-k treated children when compared to children wearing spectacles. CONCLUSIONS: This study showed that PR ortho-k with spectacles for correcting residual refractive errors is safe and can be offered to high myopic children who wish to undergo ortho-k treatment for myopic control. This mode of treatment can retard myopic progression in high myopic children.

Description: xv, 143 leaves : ill. (some col.) ; 30 cm.; PolyU Library Call No.: [THS] LG51 .H577M SO 2012 Charm

Mapping of myopia susceptibility genes using population-based association studies (case-control studies)

Sat, 01 Jan 2011 00:00:00 GMT

Title: Mapping of myopia susceptibility genes using population-based association studies (case-control studies)

Authors: Lo, Ka-kin

Abstract: Myopia is the most common eye disorder in the world. The prevalence of myopia is up to 30% in western countries, but may be as high as 80% in some Chinese populations. A refractive error in excess of -6.00 diopters (D) is defined as high myopia, also called pathologic myopia because of its associated potential eye complications, which can lead to blindness. The prevalence of high myopia can reach as high as 24% in Chinese populations while it is only up to 5% in western countries. The present case-control study started with recruitment of Chinese subjects who were highly myopic (≤ -6.0 D or worse, n=300) or emmetropic (within ±0.75 D, n=300). The first genetic association study was a replication study for the myocilin (MYOC) gene and the second study was a separate study exploring candidate genes in the MYP2 region by a DNA pooling approach, followed by confirmation using individual genotyping. Several studies have reported the association of several MYOC polymorphisms with high myopia, including one family-based study from our group. However, other studies reported negative findings. We attempted to replicate previous studies in a case-control study involving 300 cases and 300 controls. MYOC polymorphisms previously found associated with high myopia were genotyped together with other SNPs in strong linkage disequilibrium with the positive markers: two microsatellites and eight single nucleotide polymorphisms (SNPs) in total. Five correlated SNPs at the 3’ end of the gene showed significant differences between high myopes and controls under three genetic models tested (genotypic, additive and allelic): rs12076134, rs1602244, rs6425356, rs10737323 and rs743994. The results remained significant after correction for multiple comparisons by false discovery rate at 0.05 levels. The two most significant associations with rs64252356 and rs743994 were further confirmed in our original families. These SNPs have not been investigated by any other groups up to date. Three polymorphisms previously associated with high myopia failed to be replicated, suggesting that the original positive results were probably chance findings. One previously positive SNP failed to be replicated because of local variation in the linkage disequilibrium patterns in the case-control subjects.; Previous studies using linkage analysis of families with highly myopic members identified a myopia locus at chromosome 18p11 the MYP2 locus. We selected seven candidate genes (CLUL1, EMLIN-2, LPIN2, MYOM1, MYL12A, MYL12B and ZFP161) from the MYP2 region and examined 62 tag SNPs with a two-stage DNA pooling approach. In the first stage, 6 case pools and 6 control pools were constructed using DNA samples from 300 high myopes and 300 controls. Each DNA pool was prepared by mixing equal amounts of DNA from 50 distinct subjects of the same affection status. Allele frequencies of SNPs were estimated by analysis of primer-extended products in a denaturing high performance liquid chromatography system, and compared across 3 replicates of each pool and across two sets of pools by means of nested analysis of variance. In the second stage, nine promising SNPs (P ≤ 0.10) were further evaluated by individual genotyping of samples included in the pools. One SNP (rs589318) within the LPIN2 gene was found to be associated with high myopia under three genetic models (genotypic, additive and allelic), and the significance survived correction by false discovery rate at 0.05 level. This is a novel finding not previously reported. In conclusion, the results of the present study implicated the involvement of 3' polymorphisms of the MYOC gene in the predisposition to high myopia. Moreover, we successfully applied a DNA pooling strategy to screen candidate genes in the MYP2 region and identified the LPIN2 gene to be associated with high myopia. These are novel findings and should be replicated using independent sample sets.

Description: xxii, 339 p. : ill. (some col.) ; 30 cm.; PolyU Library Call No.: [THS] LG51 .H577P SO 2011 LoK