Objetivos: Avaliar a função e estrutura da retina de pacientes com membrana epirretiniana (MER) ou buraco macular (BM) antes e após a cirurgia, e determinar suas relações e os valores preditivos para a acuidade visual após tratamento com vitrectomia associada a peeling da membrana limitante interna. Casuística e Métodos: Foram incluídos 51 olhos de 50 pacientes com indicação de tratamento cirúrgico de MER ou BM idiopáticos. Foi realizada avaliação oftalmológica completa, incluindo melhor acuidade visual corrigida (MAVC) no pré-operatório e nas semanas 1, 3, 8, 24 e 48 após a cirurgia, enquanto que eletrorretinografia multifocal (mfERG) e tomografia de coerência óptica (OCT) foram realizadas antes da cirurgia e dois e doze meses após o procedimento. Os resultados da mfERG serão apresentados na forma da razão entre os valores encontrados nos dois anéis centrais, normalizados pelas médias dos três anéis periféricos (denominada razão P1), para minimizar a variabilidade interpessoal desse teste e ressaltar as alterações encontradas nos anéis centrais. A OCT foi usada para calcular o quociente entre medidas da altura e base do BM (IBM). Resultados: Quarenta e cinco pacientes (46 olhos; n = 30 BM e 16 MER) completaram as 48 semanas de seguimento. No pré-operatório, a média ± SE da MAVC (logMAR) para os grupos BM e MER, respectivamente, foi: 0,93 ± 0,22 (20/170; ou 0,12 decimal) e 0,58 ± 0,11 (20/76; ou 0,26 decimal), com melhora significativa após 48 semanas de seguimento (média ± EP da diferença entre as acuidades visuais medidas em logMAR em 48 semanas e a basal) -0,25 ± 0,07 para o grupo BM e -0,29 ± 0,06 para o grupo MER. O mfERG mostrou-se alterado antes da cirurgia para BM, com melhora da razão P1 após a cirurgia. Para o BM, houve correlação entre a razão P1 no pré-operatório e o ganho da MAVC na semana 8 após a cirurgia (r = -0,42; p = 0,033), mas essa correlação não foi observada para o grupo MER. Também não houve correlação entre o IBM e a acuidade visual após a cirurgia. Conclusões: Os resultados indicam que pacientes com BM apresentando mfERG com baixa razão P1 têm menor probabilidade de ganho de visão após a cirurgia, mas essa afirmativa não é válida para a MER. / Purpose: To evaluate retinal structure and function in eyes with macular hole (MH) or epiretinal membrane (ERM) before and after pars-plana vitrectomy with internal limitant membrane (ILM) peeling, to determine function/structural interrelations and predictive values of postoperative visual acuity. Casuistic and Methods: Fifty-one eyes of 50 patients with idiopathic MH or ERM were included. Comprehensive ophthalmologic evaluation including best-corrected visual acuity (BCVA) was performe date baseline, 1, 3, 8, 24 e 48 weeks after surgery, while optical coherence tomography (OCT) and multifocal ERG was performed before and at 2 and 12 months after surgery. mfERG results are show using the ratio between the amplitude averages of the 2 central rings and the 3 peripheral rings (P1 ratio) and OCT was used to calculate the macular hole index (MHI) defined by the quotient between hole height/base. Results: Forty-five patients (46 eyes; n = 30 MH and 16 ERM) finished follow-up. Mean ± SE (logMAR) preoperative BCVA was 0.93 ± 0.22 and 0.58 ± 0.11 for MH and ERM respectively, and improved in -0.25 ± 0.07 logMAR for MH and -0.29 ± 0.06 logMAR for ERM. mfERG P1 ratio was reduced in BM, and increased significantly after surgery. There was significant correlation between preoperative P1 ratio and BCVA gainat week 8 for MH group (r = -0,42; p = 0,033), but not for ERM group. There was no correlation between preoperative MHI and postoperative BCVA. Conclusion: This data indicates that patients with MH and poor mfERG amplitudes have worse prognoses for BCVA improvement, but does not apply for ERM.

Objetivos: Avaliar a função e estrutura da retina de pacientes com membrana epirretiniana (MER) ou buraco macular (BM) antes e após a cirurgia, e determinar suas relações e os valores preditivos para a acuidade visual após tratamento com vitrectomia associada a peeling da membrana limitante interna. Casuística e Métodos: Foram incluídos 51 olhos de 50 pacientes com indicação de tratamento cirúrgico de MER ou BM idiopáticos. Foi realizada avaliação oftalmológica completa, incluindo melhor acuidade visual corrigida (MAVC) no pré-operatório e nas semanas 1, 3, 8, 24 e 48 após a cirurgia, enquanto que eletrorretinografia multifocal (mfERG) e tomografia de coerência óptica (OCT) foram realizadas antes da cirurgia e dois e doze meses após o procedimento. Os resultados da mfERG serão apresentados na forma da razão entre os valores encontrados nos dois anéis centrais, normalizados pelas médias dos três anéis periféricos (denominada razão P1), para minimizar a variabilidade interpessoal desse teste e ressaltar as alterações encontradas nos anéis centrais. A OCT foi usada para calcular o quociente entre medidas da altura e base do BM (IBM). Resultados: Quarenta e cinco pacientes (46 olhos; n = 30 BM e 16 MER) completaram as 48 semanas de seguimento. No pré-operatório, a média ± SE da MAVC (logMAR) para os grupos BM e MER, respectivamente, foi: 0,93 ± 0,22 (20/170; ou 0,12 decimal) e 0,58 ± 0,11 (20/76; ou 0,26 decimal), com melhora significativa após 48 semanas de seguimento (média ± EP da diferença entre as acuidades visuais medidas em logMAR em 48 semanas e a basal) -0,25 ± 0,07 para o grupo BM e -0,29 ± 0,06 para o grupo MER. O mfERG mostrou-se alterado antes da cirurgia para BM, com melhora da razão P1 após a cirurgia. Para o BM, houve correlação entre a razão P1 no pré-operatório e o ganho da MAVC na semana 8 após a cirurgia (r = -0,42; p = 0,033), mas essa correlação não foi observada para o grupo MER. Também não houve correlação entre o IBM e a acuidade visual após a cirurgia. Conclusões: Os resultados indicam que pacientes com BM apresentando mfERG com baixa razão P1 têm menor probabilidade de ganho de visão após a cirurgia, mas essa afirmativa não é válida para a MER. / Purpose: To evaluate retinal structure and function in eyes with macular hole (MH) or epiretinal membrane (ERM) before and after pars-plana vitrectomy with internal limitant membrane (ILM) peeling, to determine function/structural interrelations and predictive values of postoperative visual acuity. Casuistic and Methods: Fifty-one eyes of 50 patients with idiopathic MH or ERM were included. Comprehensive ophthalmologic evaluation including best-corrected visual acuity (BCVA) was performe date baseline, 1, 3, 8, 24 e 48 weeks after surgery, while optical coherence tomography (OCT) and multifocal ERG was performed before and at 2 and 12 months after surgery. mfERG results are show using the ratio between the amplitude averages of the 2 central rings and the 3 peripheral rings (P1 ratio) and OCT was used to calculate the macular hole index (MHI) defined by the quotient between hole height/base. Results: Forty-five patients (46 eyes; n = 30 MH and 16 ERM) finished follow-up. Mean ± SE (logMAR) preoperative BCVA was 0.93 ± 0.22 and 0.58 ± 0.11 for MH and ERM respectively, and improved in -0.25 ± 0.07 logMAR for MH and -0.29 ± 0.06 logMAR for ERM. mfERG P1 ratio was reduced in BM, and increased significantly after surgery. There was significant correlation between preoperative P1 ratio and BCVA gainat week 8 for MH group (r = -0,42; p = 0,033), but not for ERM group. There was no correlation between preoperative MHI and postoperative BCVA. Conclusion: This data indicates that patients with MH and poor mfERG amplitudes have worse prognoses for BCVA improvement, but does not apply for ERM.

La myopie est désormais considérée un problème de santé publique par l’Organisation Mondiale de la Santé et de multiples méthodes ont été mises en place afin de contrôler sa progression chez les jeunes en croissance. Parmi celles-ci, les lentilles cornéennes multifocales sont utilisées, permettant une focalisation au niveau de la rétine centrale et un défocus myopique en périphérie. Ce défocus rétinien aurait comme effet de diminuer la progression de la myopie et l’élongation du globe oculaire. Comme plusieurs études ont montré que la rétine est apte à percevoir le défocus et à différencier son sens, l’utilisation d’outils tels que l’électrorétinographie permet d’étudier ce phénomène plus en profondeur. Cette étude vise donc à mesurer la réponse rétinienne, à 5 différentes excentricités, avec l’électrorétinographie lorsqu’on soumet la rétine à un défocus myopique en utilisant des lentilles cornéennes multifocales à addition élevée et à comparer cet effet lorsque le diamètre de leurs zones optiques varie. Le flash global mfERG a été effectué sur 27 participants à trois reprises, soit avec une lentille cornéenne ne causant pas de défocus et avec deux lentilles multifocales ayant des zones optiques de différents diamètres (4mm et 7mm), permettant ainsi de varier l’aire du défocus. Les résultats montrent que l’amplitude de l’onde directe, causée principalement par les photorécepteurs et les cellules bipolaires, n’est pas influencée par le design des lentilles. L’amplitude de l’onde induite est toutefois diminuée de façon significative avec la LC ayant une zone optique plus petite et causant un défocus sur une plus grande surface rétinienne. Cette différence est présente au niveau de l’anneau 5, qui correspond à une excentricité rétinienne de 15,7o à 24,0o. Ceci précise l’endroit qui semblerait le plus sensible au défocus myopique. Ces données peuvent influencer le design des lentilles souples multifocales utilisées pour le contrôle de la myopie. / Myopia is now considered a public health issue by the World Health Organization and multiple methods have been developed to control its progression. Among these methods, soft multifocal contact lenses are used, which allow a focused image on the central retina and a myopic defocus peripherally. This retinal defocus impacts the progression of myopia and axial length. Since several studies have shown that the retina is sensitive to the type of defocus, the use of tools such as electroretinography allow the study of the retinal response in greater depth. The purpose of this study was to evaluate the retinal response, at 5 different eccentricities, with electroretinography when the retina is subjected to myopic defocus using different high addition soft multifocal contact lenses and to compare this effect when the diameter of their optical zones varies. 27 participants performed a global flash mfERG three times, either with a single vision contact lens or with two multifocal lenses carrying different optical zone diameters (4mm and 7mm), allowing for the variation in defocus area. The results show that the amplitude of the direct wave, caused mainly by photoreceptors and bipolar cells, is not influenced by the design of the lenses. The amplitude of the induced wave, however, is significantly decreased when the optical zone is smaller and the lenses cause a defocus over a larger retinal area. This difference is present at ring 5, which corresponds to a retinal eccentricity of 15.7o to 24.0o. This specifies the location that would appear to be most sensitive to myopic defocus. This data may influence the design of multifocal soft lenses used for myopia control.

Studies demonstrate neuro-retinal damage in patients with diabetes and no clinically visible diabetic retinopathy. It is unknown which retinal regions are most vulnerable to diabetes. We hypothesized that the standard and slow-flash (sf-) multifocal electroretinogram (mfERG) and adaptive optics (AO) imaging will localize retinal regions of vulnerability. Fifty-five adolescents with diabetes and 54 controls underwent mfERG testing to isolate predominately retinal bipolar cell activity and sf-mfERG testing to isolate three oscillatory potentials (OPs) from intraretinal amacrine and interplexiform cells. Greatest mfERG delays were in the superior temporal quadrant and at 5°-10° eccentricity. Greatest sf-mfERG delays were found at different eccentricities for each OP. Twenty adolescents with diabetes and 14 controls underwent AO imaging. No significant differences in cone photoreceptor density were found; however, patients showed a trend towards reduced density in the superior nasal region. Inner retinal structures may be more susceptible to damage by diabetes than outer retinal structures.

Studies demonstrate neuro-retinal damage in patients with diabetes and no clinically visible diabetic retinopathy. It is unknown which retinal regions are most vulnerable to diabetes. We hypothesized that the standard and slow-flash (sf-) multifocal electroretinogram (mfERG) and adaptive optics (AO) imaging will localize retinal regions of vulnerability. Fifty-five adolescents with diabetes and 54 controls underwent mfERG testing to isolate predominately retinal bipolar cell activity and sf-mfERG testing to isolate three oscillatory potentials (OPs) from intraretinal amacrine and interplexiform cells. Greatest mfERG delays were in the superior temporal quadrant and at 5°-10° eccentricity. Greatest sf-mfERG delays were found at different eccentricities for each OP. Twenty adolescents with diabetes and 14 controls underwent AO imaging. No significant differences in cone photoreceptor density were found; however, patients showed a trend towards reduced density in the superior nasal region. Inner retinal structures may be more susceptible to damage by diabetes than outer retinal structures.

Age-related maculopathy (ARM) is a central retinal disease with unclear pathogenesis. It is the major cause of permanent vision loss in adults over 50 years and is increasing in prevalence and incidence, faster than the aging population would suggest. Early in the disease process (early ARM) there is little or no vision loss and there are only slight retinal changes with abnormal deposits within Bruch's membrane. As the disease progresses (late ARM or age-related macular degeneration, AMD) vision loss may be quite severe due to atrophy (dry AMD) or the development of chorioretinal neovascularisation (CNV, wet AMD). It is hard to predict from conventional eye examinations and clinical vision tests which cases will progress to the severe, dry or wet forms of the disease. Moreover, most of the conventional clinical tests are based upon subjective vision measures. Objective tests which detect ARM earlier would be a useful aid to diagnosis and to monitoring progression. The multifocal electroretinogram (mfERG) is a relatively new clinical tool which enables the recording of electrical potentials from multiple, small areas of the central retina and thus assesses function from specific retinal locations. It is therefore useful in detecting focal retinal diseases such as hereditary or acquired maculopathies or in monitoring retinal laser or surgical treatment effects. There is cone and rod impairment in ARM and histopathological and psychophysical evidence for a preferential vulnerability of rods compared to cones. This research project investigated if an objective tool such as the mfERG could detect early ARM,its progression and the treatment effects of multiple photodynamic therapies (PDT) on retinal function in late ARM, prior to a battery of subjective vision measures. For comparison purposes a subjective assessment of central retinal function was performed using high and low contrast distance visual acuities (VA), near VA, low luminance VA (SKILL cards), contrast sensitivity (Pelli-Robson, P-R), saturated and desaturated Panel D-15 (sat Panel D-15, desat Panel D-15) and central visual fields (Humphrey 10-2, mean sensitivity, MS and mean defects, MD). As an objective assessment of central retinal function the cone- and rod-mediated multifocal electroretinograms were recorded. Subjective and objective tests of retinal function were compared in early ARM and an age-matched control group (chapter 3). Seventeen eyes of seventeen subjects with early ARM and twenty control subjects with normal vision were measured. For the cone-mediated mfERG responses conventional averaging methods were used and results were correlated with subjective vision tests. The conventional cone-mediated mfERG failed to distinguish between the early ARM and control subjects whereas subjective vision measures such as HC- and LC-VA, desat Panel D-15, MS, P-R were significantly reduced in the ARM group. However, there were significant correlations between the cone-mediated mfERG and the desat Panel D-15 results in the ARM group. This suggests that the mfERG measures similar retinal processes that detect colour vision deficiency under desaturated conditions. There was no significant correlation between cone-mediated mfERG measures and funduscopic changes. The conclusion from this study was that the subjective vision tests detected early ARM better than the objective cone-mediated mfERG. Thus the aim of detecting early ARM objectively was not met by the cone-mediated mfERG suggesting the need to develop other objective tests such as a rod-mediated mfERG. Whether the preferential rod vulnerability others have reported in early ARM could be detected by the rod-mediated mfERG was determined in the next study (chapter 4). A protocol for recording rod-mediated mfERG responses was developed by determining the optimal testing luminance to reduce the effect of stray light and elicit maximal rod-mediated responses. Sixteen of the seventeen ARM subjects and seventeen control subjects from the previous study were tested. For analysis, a customized computer template fitting method was developed in MATLAB (Mathworks, Natick, MA, USA). This method has been shown to be useful for low signal-to-noise ratio responses that characterize the rod-mediated mfERG. Significantly delayed rod-mediated mfERG responses were found whereas cone-mediated mfERG responses were within the normal range. This suggested that the effect of ARM on the rod system could be detected objectively with the rod-mediated mfERG before changes in the cone-mediated mfERG. Which of the tests best detected progression of vision loss was investigated in chapter 5. Visual function of 26 (13 ARM and 13 control subjects) of the original 37 subjects (17 ARM and 20 control subjects) had cone- and rod-mediated mfERG and the subjective vision measures repeated after one year. The main purpose was to determine which of the tests best detected progression of vision loss. The mfERG results were analysed by using both averaged and local responses and by using the computer template fitting procedure. On average no significant worsening of either objective or subjective function measures was evident after one year. These results reinforce the slow progression of the disease. With a longer follow-up period progression of ARM may translate into measurable changes in the mfERG and the other visual function tests. The effect of multiple photodynamic therapies (PDT) on cone- and rod-mediated function was assessed with the mfERG in the last study (chapter 6). The cumulative treatment effects of PDT in five subjects with late ARM were determined. Having demonstrated that the rod-mediated mfERG was applicable in early ARM, this study also aimed to investigate how useful it was in late ARM where there is substantially greater rod loss. Cone- and rod-mediated mfERGs, visual acuities, contrast sensitivities and central visual fields were investigated a week before treatment began and then one month after each PDT treatment. The subjects received three treatments each over an average period of five and a half months. In some subjects there were significant transient reductions in cone- and rod-mediated amplitudes possibly reflecting alterations in choroidal hypoperfusion dynamics one month after treatment. Further, b-wave component of the mfERG became increasingly misshapen after each PDT treatment suggesting an ischemic insult mainly targeting post-receptoral sites. However, objective and subjective function was stabilized after multiple PDT treatments in most of the subjects. This pilot study of five cases showed that there was no additional damage to cone- and rod-mediated outer retinal function after three PDT treatments. One of the novel findings of this research was that the rod-mediated function measured with the mfERG was impaired in early ARM. This finding supports histopathological and psychophysical evidence of rod vulnerability in early ARM. The results of these studies also suggest that early ARM affects different aspects of visual function which is reflected by different outcomes from objective and subjective vision tests. A model (chapter 7) based upon the results was developed proposing a hypoxic insult with a preferential alteration of post-receptoral sites in early ARM. The cone-mediated mfERG documented the retinal damage and possible treatment effects on outer retinal function of the multiple PDTs which did not further deteriorate. Thus, this technique might assist in the development of optimal treatment modalities for ARM, especially in retreatment regimes. Greater variability was found for the rod-mediated mfERG and its clinical use in PDT treatment regimes still needs to be investigated. In conclusion, this research has provided a better understanding of the disease process and treatment effects in ARM and might contribute to improvements in diagnosis and treatment of ARM.