Doctoral Degrees (Ophthalmology)

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    Congenital and genetic disruptions of human ocular motility and alignment – phenotypic / genotypic bi-directional algorithm
    (Stellenbosch : Stellenbosch University, 2019-04) Oystreck, Darren T; Meyer, David; Stellenbosch University. Facult of Medicine and Health Sciences. Dept. of Surgical Sciences: Ophthalmology
    ENGLISH ABSTRACT: Our understanding of congenital and genetic disruption to human ocular motility and alignment has expanded significantly over the past 15 years due in large part to advances in genetics. This has permitted identification of many underlying genetic causes in several conditions and provided new insight into the development and function of the oculomotor system. However, this information has also disturbed current classification systems based almost exclusively on ocular motility characteristics resulting in a knowledge gap between clinicians and researchers. As part of a team of researchers from several institutions a series of studies were conducted to better elucidate the clinical and genetic features in a large heterogeneous group of subjects with known or suspected congenital or genetic disorders affecting ocular motility and alignment. This dissertation is the outcome of this work. It also provided an opportunity to assess the value of the orthoptic evaluation by critically evaluating ocular motility and alignment patterns in this population. The main objective was to identify key patterns that can be used to predict underlying genotypes. This could provide a more rapid, cost effective approach to these disorders and better define the role for the general ophthalmologist in the investigation. This work spans over a decade and resulted in 47 publications that provide key pieces to the expanding body of knowledge in this field. Several publications served as reviews for knowledge translation for the ophthalmologist and one focuses on summarizing the orthoptic evaluation. In total 845 enrolled subjects received orthoptic evaluations. This included 40 different diagnoses and 25 different genes with mutations identified. The orthoptic information in these subjects formulated part of all research team publications. Despite only scratching the surface of the entire domain of genetic ocular motility and alignment disorders, this is likely is the largest and broadest collection of diagnoses in one report. A new classification scheme is proposed, one that is based on the underlying pathomechanisms accounting for disruption to ocular motility and alignment. A simplified clinical approach has been developed for the general ophthalmologist to utilize key orthoptic assessments as aids in appropriately classifying encountered subjects. This is important as each diagnostic category of conditions generally requires different investigations and management. This research also identified significant phenotypic overlap in genetically distinct disorders and phenotypic variability in the same genetic disorder. Therefore it is concluded that orthoptic features in isolation cannot be used to reliability predict the underlying genotype. The addition of information from other medical specialties improves this prediction. However, due to the currently small number of genotyped individuals in many of these rare disorders, more research is required before definitive genotype-phenotype spectrums can be identified. It is also emphasizes the need for standardization of the orthoptic assessment and reporting of the findings to ensure that similarities and differences be identified accurately.
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    A critical appraisal of the etiology of adult human lenticular opacification and an investigation into the role of metabolic factors in its pathogenesis
    (Stellenbosch : Stellenbosch University, 2001-12) Meyer, David; Parkin, D. P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Surgical Sciences. Ophthalmology.
    ENGLISH ABSTRACT: The eye is that biological instrument which conveys the light of the external world into the inner world of the mind, wherein we receive the miraculous gift of vision. So precious is this gift, that Science must search for ways to keep this portal clear for the flow of light. Indeed, Science is called upon to “make war upon the bloody tyrant, Time.” (Shakespeare W. Sonnet No. 16). For, in the course of ageing, the lens grows cloudy and cataractous. In this battle between Science and Time, we are fortunate to live in an era in which Science is uncovering the molecular basis for the various obstacles to vision. The question arises, whether or not, the ruinous hand of time can be stayed. Due to unrelenting, progressive lens opacification, most of the elderly are destined to be subjected to loss of vision and with passage of time, even blindness. Globally the cataract surgery rate is inadequate to keep pace with the ever growing demand on financial and human resources created by the cataract problem. An immense challenge therefore is directed to primary eye care: “Can cataract be prevented or can its onset at least be postponed?” This laudable ultimate aim can only be achieved once the etiology of cataractogenesis is well understood. This dissertation seeks to examine two previously unrecognized etiological aspects that, if correctly understood and managed, have the potential to achieve preventive ophthalmological goals that may indeed help to stay the ‘ruinous hand of time’. The first aspect deals with the role of lipids and was examined using a study group of dyslipidemic subjects. The first part of the study concluded that dyslipidemic patients develop cortical lens opacities more frequently and at an earlier age than the normal population, and that cortical lens opacities should be regarded as one of the most reliable clinical signs of dyslipidemia. Furthermore, an extremely strong correlation was found to exist between low HDL Cholesterol levels and the development of opacities. Below a HDL-Cholesterol level of 1,5mmol/l, subjects had more than seven-fold higher risk of falling in the lens opacity subgroup than those with HDLCholesterol levels above 1,5mmol/l. An equally strong correlation was demonstrated between high (>5) LDLHDL ratios and the development of lens opacities. Subjects with a LDL:HDL-C ratio below 5 possessed a 2.35 times greater risk of having lenticular opacities than the group with a LDL:HDL-C ratio greater than 5. The prevention or retardation of dyslipidemia associated lens opacities is therefore possible, provided patients with a genetic predisposition are detected early and their blood lipids managed adequately. The second aspect deals with the relationship between age related cataracts and the acetylation status of the individual. This study compellingly submits that the slow acetylator pheno- and genotype may be regarded as a genetic indicator of risk for age related cataract. The ability accurately to classify a patient genotypically and phenotypically, may henceforth be useful in health counseling since, if an individual is identified as being a slow acetylator, additional preventative and precautionary measures may be taken, i.e. the prevention of UVexposure to the eye and caution with the ingestion of xenobiotics like caffeine, commercial dyes, food preservatives, and drugs. Furthermore, such a finding should be taken into account in the long term therapeutic management of glaucoma, with special regard to carbonic anhydrase inhibitors which are sulphonamide-related drugs and totally dependent on the N-acetyltransferase pathway for metabolism. These drugs may accumulate in the slow acetylator over time and exert toxic effects intra-ocularly, conceivably including cataractogenesis. The search for genetic and metabolic mechanisms that may contribute to human cataractogenesis should be pursued with great enthusiasm. This endeavour may help Science to achieve its primary objective, ablate the effects of Time and really aid in preventing cataracts in man.
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    Outcome of primary adult optical penetrating keratoplasty in a public health service facility of a developing country
    (Stellenbosch : Stellenbosch University, 2008-12) Wagoner, Michael D.; Meyer, David; Stellenbosch University. Faculty of Health Sciences. Dept. of Surgical Sciences. Ophthalmology.
    Purpose: To evaluate the outcome of primary adult optical penetrating keratoplasty (PKP) at a public health service hospital of a developing country. Patients and Methods: A retrospective review was performed of the medical records of every patient 12 years of age or older who underwent PKP for keratoconus, corneal edema, stromal scarring, or stromal dystrophy at King Khaled Eye Specialist Hospital in the Kingdom of Saudi Arabia between January 1, 1997, and December 31, 2001, and for whom a minimum of 3 months’ follow-up was available. Results: Of 910 eyes that met the inclusion criteria, there were 464 eyes with keratoconus, 188 eyes with corneal edema, 175 eyes with stromal scarring, and 83 eyes with stromal dystrophy. For the entire group, the probability of graft survival was 96.7% at 1 year, 86.2% at 3 years, and 80.9% at 5 years. Five-year survival probability was best with keratoconus (96.1%), followed by stromal dystrophy (85.9%), stromal scarring (71.1%), and corneal edema (40.3%). The probability of graft survival differed significantly among the surgical indications at all postoperative intervals (P<0.001). Factors associated with a significantly increased risk of graft failure on multivariate Cox proportional hazard regression analysis included increasing donor tissue age (P = 0.005) and decreasing recipient graft size (P = 0.02). Final visual acuity of 20/40 or better was obtained in 409 (44.9%) eyes. Visual acuity of 20/40 or better was obtained in 336 (72.4%) eyes with keratoconus and in 53 (63.9%) eyes with stromal dystrophy but in only 11 (6.3%) eyes with stromal scarring and 9 (4.8%) eyes with corneal edema (P<0.001). Overall, improvement in vision occurred in 750 (82.4%) eyes, remained the same in 97 (10.7%) eyes, and worsened in 63 (6.9%) eyes. Conclusions: The present study has conclusively demonstrated that primary adult optical PKP can be performed at a public health facility in the Kingdom of Saudi Arabia with graft survival and visual results that are comparable to those obtained in welldeveloped Western facilities. This success is attributed to the presence of a suitable infrastructure that provides modern eye care facilities, donor tissue, and pharmaceuticals to patients who have access to preoperative screening and evaluation, surgical intervention, and postoperative care by well-trained ophthalmologists and ancillary support personnel.