Magnetic Resonance Imaging (MRI) is an imaging modality that acquires an image with little to no damage to the tissue. MRI does not introduce foreign particles or high energy radiation into the body, making it one of the least invasive medical imaging modalities. MRI can achieve excellent soft tissue contrast and is therefore useful for diagnosis of a wide variety of diseases. While there are a wide variety of available techniques for generating contrast in MRI, there are still many open areas for research. For example, many tissues in the human body exhibit such rapid signal decay that they are difficult to image with MRI: they are "MRI invisible". Furthermore, some of the newer MRI imaging techniques have not been fully validated to ensure that they are truly revealing accurate information about the underlying anatomical microstructure that they purport to image. This dissertation focuses on the development of new techniques in two distinct areas. First, a novel method for accurately assessing the MRI signal decay properties of tissues that are normally MRI invisible, such as tendons, ligaments, and certain pathological chemical deposits in the brain, is presented. This is termed "ultrashort MRI relaxometry". Second, two new image processing algorithms that operate on high resolution images of stained histological slices of the ex vivo brain are presented. The first of these image processing algorithms allows the semi-automated extraction of nerve fiber directionality from the histological slice images, a process that is normally done manually, is incredibly time consuming, and is prone to human error. This new technique represents one significant step in the complicated problem of attempting to validate a popular MRI technique, Diffusion Tensor Imaging (DTI), by ensuring that DTI results correlate with the true underlying physiology revealed by histological slicing and staining. The second of these image processing algorithms attempts to extract and segment regions of different "cytoarchitectonic characteristics" from stained histological slices of ex vivo brain. Again, traditional cytoarchitectonic segmentation relies on manual segmentation by an expert neuroanatomist, which is slow and sometimes inconsistent. The new technique is a first step towards automated this process, potentially providing greater accuracy and repeatability of the segmentations in a much shorter time. Together, these contributions represent a significant contribution to the body of MR imaging techniques, and associated image processing techniques for validation of newer MR neuroimaging techniques against the gold standard of stained histological slices of ex vivo brain.

OBJETIVO: Avaliar a capacidade dos parâmetros do eletrorretinograma de padrão reverso de campo total e hemianópico em diferenciar olhos com atrofia em banda do nervo óptico e, a correlação entre as amplitudes do eletrorretinograma de padrão reverso, a espessura da camada de fibras nervosas da retina e macular obtidas pela tomografia de coerência óptica e a perda de campo visual nestes pacientes. MÉTODOS: Quarenta e um olhos de 41 pacientes com perda de campo visual temporal permanente por compressão do quiasma óptico e 41 controles normais foram submetidos ao eletrorretinograma de padrão reverso de estimulação de campo total e hemianópicos (temporal e nasal), a tomografia de coerência óptica, para avaliação das medidas da espessura da camada de fibras nervosas da retina e macular e, ao exame de campo visual, pela perimetria automatizada padrão. O desvio do normal da sensibilidade dos 18º centrais do campo visual foram expressos em decibéis e unidades 1/Lambert. As comparações foram feitas pelo teste t de Student. A correlação entre os parâmetros do campo visual central, do eletrorretinograma de padrão reverso e da tomografia de coerência óptica foi avaliada pela correlação de Pearson e análise de regressão linear. RESULTADOS: Os valores das amplitudes P50, N95, and P50+N95 do eletrorretinograma de padrão reverso de campo total, e de estimulação hemianópica e os valores das medidas da espessura macular e da camada de fibras nervosas da retina obtidas pela tomografia de coerência óptica foram significativamente menores nos olhos com atrofia em banda do que nos controles (P<0,001). Uma correlação significativa foi encontrada entre a perda de sensibilidade no campo visual central e as amplitudes do eletrorretinograma de padrão reverso de estimulação de campo total e nasal, mas não para o temporal. Uma correlação significativa positiva foi observada entre os parâmetros de perda de sensibilidade no campo visual e a maioria dos parâmetros da espessura da camada de fibras nervosas da retina e macular obtidas pela tomografia de coerência óptica. Nenhuma correlação significativa foi observada entre os parâmetros do eletrorretinograma de padrão reverso e a tomografia de coerência óptica, exceto para amplitude P50+N95 do eletrorretinograma de padrão reverso de estimulação de hemicampo nasal. Uma correlação significativa foi observada entre os parâmetros de espessura macular e da camada de fibras nervosas pela tomografia de coerência óptica, exceto entre a espessura da camada de fibras nervosas no segmento de 30º, correspondente as 9 horas do relógio e os parâmetros maculares. CONCLUSÕES: Os valores das amplitudes do eletrorretinograma de padrão reverso foram eficazes em diferenciar olhos com atrofia em banda do nervo óptico de controles normais. Em pacientes com atrofia em banda do nervo óptico, as amplitudes do eletrorretinograma de padrão reverso e medidas da espessura da camada de fibras nervosas da retina e macular correlacionaram de forma significativa com a perda de campo visual, mas não houve correlação entre eles. O eletrorretinograma de padrão reverso e a tomografia de coerência óptica detectaram a perda neural e ambos são métodos diagnósticos úteis na compreensão da correlação estrutura-função em pacientes com compressão do quiasma óptico / PURPOSE: To evaluate the ability of full-field and hemifield pattern electroretinogram parameters to differentiate between healthy eyes and eyes with band atrophy of the optic nerve and also to evaluate the relationship between pattern electroretinogram amplitude, macular and retinal nerve fiber layer thickness by optical coherence tomography, and visual field loss on standard automated perimetry in eyes with BA of optic nerve. METHODS: Forty-one eyes from 41 patients with permanent temporal visual field defects from chiasmal compression and 41 healthy subjects underwent transient fullfield and hemifield (temporal or nasal) stimulation pattern electroretinogram, standard automated perimetry and time domain- optical coherence tomography macular and retinal nerve fiber layer thickness measurements. Comparisons were made using Students t-test. Deviation from normal visual field sensitivity for the central 18° was expressed in dB and 1/Lambert units. Correlations between measurements were verified by Pearsons correlations and linear regression analysis. RESULTS: Full-field P50, N95, and P50+N95 amplitude values were significantly smaller in eyes with band atrophy than in control eyes (P<0.001). Nasal and temporal hemifield pattern electroretinogram studies revealed significant differences in N95 and P50+N95 amplitudes measurements. Pattern electroretinogram and optical coherence tomography measurements were significantly lower in eyes with temporal hemianopia than in normal eyes. A significant correlation was found between visual field sensitivity loss and full-field or nasal, but not temporal, hemifield pattern electroretinogram amplitude. Likewise a significant correlation was found between visual field sensitivity loss and most optical coherence tomography parameters. No significant correlation was observed between optical coherence tomography and pattern electroretinogram parameters, except for nasal hemifield amplitude. A significant correlation was observed between several macular and retinal nerve fiber layer thickness parameters. CONCLUSIONS: Transient pattern electroretinogram amplitude measurements were efficient at differentiating eyes with band atrophy and permanent visual field defects from normal controls. In patients with chiasmal compression, pattern electroretinogram amplitude and optical coherence tomography thickness measurements were significant related to visual field loss, but not to each other. Pattern electroretinogram and optical coherence tomography quantify neuronal loss differently, but both technologies are useful in understanding structure-function relationship in patients with chiasmal compression

This work deals with mathematical description of nerve fiber bundle trajectories for the diagnosis of glaucoma. Also gives a brief explanation in the principle of fundus camera and glaucoma. Its aim is to implement the model into MATLAB software, to project a~methodics of its use and also to realize it.

<p>Cilj ovog istraživanja bio je da se utvrdi razlika u debljini sloja retinalnih nervnih vlakana (RNFL) i parametara glave očnog živca kod pacijenata sa preperimetrijskim glaukomom i pacijenata sa glaukomom otvorenog ugla (POAG) u odnosu na zdravu populaciju, kao i da se utvrdi razlika u debljini RNFL i parametara glave očnog živca kod pacijenata sa POAG u odnosu na stepen progresije bolesti. Materijal i metode: U ovu kliničku, analitičku i opservacionu, po tipu &bdquo;slučaj-kontrola&ldquo; studiju, bilo je uključeno 120 pacijenata. Na osnovu kliničkog nalaza formirane su četiri grupe. Prva grupa (grupa zdravih): 30 pacijenata bez glaucoma i drugih očnih bolesti. Druga grupa (grupa sa početnim POAG): 30 pacijenata sa POAG, sa karakterističnim o&scaron;tećenjem glave očnog živca i RNFL, kod kojih je srednja vrednost devijacije standardizovane automatske perimetrije MD&lt;-6dB (prema Hodap klasifkaciji) sa karakterističnim glaukomskim ispadima u vidnom polju. Treća grupa (grupa sa srednje uznapredovalim POAG): 30 pacijenata sa POAG, kod kojih je srednja vrednost devijacije standardizovane automatske perimetrije MD od -6dB do -12dB (prema Hodap klasifkaciji). Četvrta grupa (grupa sa preperimetrijskim glaukom): 30 pacijenata sa promenama na glavi očnog živca karakterističnim za glaukomsku neuropatiju, kod kojih ne postoje funkcionalni ispadi tj. standardna automatizovana perimetrija pokazuje normalne vrednosti MD parametara (od -2 dB do +2dB). Kod svih pacijenata bio je urađen kompletan oftalmolo&scaron;ki pregled, kompjuterizovano vidno polje i optička koherentna tomografija peripapilarne regije RNFL i glave očnog živca (na aparatu Stratus OCT 3000, Carl Zeiss Meditec). Rezultati su pokazali da je debljina RNFL-a kod pacijenata sa početnim POAG manja u odnosu na zdravu populaciju. Najveće sniženje debljine RNFL je u sektorima 1,6,7 i 8h. Jedino u sektoru 4h i 9h ne dolazi do smanjenja debljine RNFL-a. Najveće smanjenje debljine RNFL je u gornjem i donjem kvadrantu, te oni imaju visoku specifičnost za diskriminaciju između zdravih i pacijenata sa početnim POAG. Parametri glave očnog živca: volumen ekskavacije, vertikalni C/D, horizontalni C/D i ukupni C/D odnos kod pacijenata sa početnim POAG povećani su u odnosu na zdravu populaciju. Parametri glave očnog živca: povr&scaron;ina neuroretinalnog oboda i volumen neuroretinalnog oboda, kod pacijenata sa početnim POAG smanjeni su u odnosu na zdravu populaciju. Debljina RNFL kod pacijenata sa srednje uznapredovalim POAG smanjena je i u odnosu na pacijente sa početnim POAG i u odnosu na zdravu populaciju (59,69&plusmn;10,63 &mu;m vs 73,44&plusmn;12,16&mu;m vs 105,57&plusmn;11,34 &mu;m). Parametri glave očnog živca prate ove promene. Ukupna povr&scaron;ina glave očnog živca se statistički značajno ne menja između zdravih osoba, pacijenata sa početnim i srednje uznapredovalim glaukomom otvorenog ugla i kod pacijenata sa preperimetrijskim glaukomom, te ovaj parametar ne determini&scaron;e glaukomsku bolest. Postojanje i napredovanje glaukoma kod pacijenata dovodi do istanjenja&nbsp; peripapilarnog RNFL &scaron;to je praćeno povećanjem ekskavacije glave očnog živca. Sa smanjenjem MD vrednosti dolazi do sledstvenih promena većine parametara. Postoji pozitivna korelacija između uznapredovalosti galukoma i srednje vrednosti debljine RNFL. Promena ove vrednosti najbolje pokazuje da dolazi do progresije POAG. Parametri glave očnog živca koji najbolje oslikavaju progresiju glaukoma su: ukupni C/D, vertikalni C/D i horizontalni C/D odnos. Debljina RNFL-a kod pacijenata sa preperimetrijskim glaukomom je značajno manja u od nosu na zdravu populaciju (83,65&plusmn;9,24&mu;m vs 105,57&plusmn;11,34&mu;m). To se posebno izražava u gornjem kvadrantu, dok u temporalnom kvadrantu ne dolazi do promena. Parametar S zajedno sa srednjom vrednosti debljine RNFL predstavljaju najbolje pokazatelje nastajanja preperimetrijskog glaukoma. Sektor 1h je sektor sa visokom specifično&scaron;ću za diskriminaciju izmeĎu zdravih i pacijenata sa preperimetrijskim glaukomom. Parametri glave očnog živca: volumen ekskavacije, vertikalni C/D, horizontalni C/D i srednji C/D odnos, kod pacijenata sa preperimetrijskim glaukomom statistički su značajno povećavani i u odnosu na zdravu populaciju. Parametri glave očnog živca: povr&scaron;ina neuroretinalnog oboda i volumen neuroretinalnog oboda, kod pacijenata sa preperimetrijskim glaukomom statistički su značajno manji u odnosu na zdravu populaciju. Najbolji prediktori nastanka i napredovanja glaukomske bolesti su sledeći parametri: AvgThic, debljina RNFL po kvadrantima-S,I,N; parametric debljine RNFL: Smax, Savg, Iavg; kao i parametri PNO: RimArea, RimVol, DiscArea, CupAear, C/DHorRat, C/DVertRat, C/DAreaRat. ROC kriva je pokazala da su sledeću parametri lo&scaron;i marker za progresiju bolesti: debljine RNFL kavdranta T, Imax i upVol. Zaključak: Određivanje parametara glave očnog živca i debljine peripapilarnih RNFL kod pacijenata sa glaukomom, optičkom koherentnom tomografijom, predstavlja metodu koja izdvaja pacijente sa preperimetrijskim glaukomom od zdrave populacije. Ono posebno ukazuje na sektore, kvadrante i parametre koji su najosetljiviji na glaukomsku noksu i koji prvi postaju patolo&scaron;ki pri nastanku glaukoma. Takođe, ukazuje i na razliku između pojedinih stepena glaukomske bolesti. Na ovaj način se omogućuje sigurna i rana dijagnoza glaukoma, njegovo pravovremeno lečenje i bolja prognoza kod pacijenata sa POAG.</p> / <p>Aim: The aim of this study was to determine the difference in thickness of retinal nerve fibre layer (RNFL) and parameters of optic nerve head in patients with preperimetric glaucoma and in patients with open angle glaucoma (POAG) in comparison to healthy population, as well as to determine the difference in thickness of RNFL and parameters of optic nerve head in patients with POAG according to progression of the disease. Material and methods: This clinical study was analytical and opservational, &bdquo;case-control&ldquo; type of study. 120 patients were included. On the basis of clinical finding 4 groups were formed. First group (healthy): 30 patients without glaucoma and with no other ocular disease. Second group (group of patients with mild POAG): 30 patients with POAG, with characteristical optic nerve head and RNFL damage, in whom the value of standard deviation of standardised automatic perimetry is MD&lt;-6dB (according to Hodap classification) with typical glaucomatous visual field defects. Third group (group of patients with moderate POAG): 30 patients with POAG in whom the mean value of standard deviation of standardised automatic perimetry, MD is from -6dB to -12dB (according to Hodap classification). Fourth group (group of patients with preperimetric glaucoma): 30 patients with changes of optic nerve head that are typical of glaucomatous neuropathy in whom there are no functional changes and with normal values of MD parameters of standardised automatic perimetry. In all patients complete ophthalmological examination, complete visual field and optic coherent tomography of peripapillar region of RNFL and optic nerve head (using Stratus OCT 3000, Carl Zeiss Meditec) were performed.The results showed that thickness of RNFL in patients with mild POAG is lesser than in healthy subjects. The greatest decrease in RNFL thickness is in sectors 1,6,7 and 8h. Only in sectors 4h and 9h there is no decrease in RNFL thickness. The greatest decrease in RNFL thickness is in upper and lower quadrant, so they are highly specific in determination between healthy subjects and patients with mild POAG. Parameters of optic nerve head such as: excavation volume, vertical C/D, horisontal C/D and total C/D ratio in patients with mild POAG are higher comparing to healthy population. Parameters of optic nerve head such as: neuroretinal rim area and neuroretinal rim volume in patients with mild POAG are lower than in healthy population. RNFL thickness in patients with moderate POAG is lesser than in patients with mild POAG, as well as in healthy subjects. Optic nerve head parameters follow these changes. Total optic nerve head area does not change in healthy subjects, in patients with mild and moderate open angle glaucoma and in patients with preperimetric glaucoma, so this parameter does not determine glaucomatous disease. The existence and progression of glaucoma in patients leads to thinning of peripapillar RNFL which is followed by increase of excavation of optic nerve head. With decrease of MD value there are consecutive changes in most parameters. There is positive correlation between progression of glaucoma and average thickness of RNFL. The change of this value shows the best if there is progression of POAG. Paremeters of optic nerve head that are the best determinants of progression of glaucoma are: total C/D, vertical C/D and horisontal C/D ratio. Thickness of RNFL in patients with preperimetric glaucoma is significantly lesser than in healthy subjects. It is particularly seen in upper quadrant, while in temporal quadrant there are no changes. Parameter S together with mean value of RNFL thickness is the best parameter of appearance of preperimetric glaucoma. Sector 1h is the sector that is highly specific in discrimination between healthy subjects and patients with preperimetric glaucoma. Optic nerve head parameters such as: volume of excavation, vertical C/D, horizontal C/D and C/D mean ratio in patients with preperimetric glaucoma are statistically significantly higher than in healthy population. Optic nerve head parameters such as: neuroretinal rim area and neuroretinal rim volume in patients with preperimetric glaucoma are statistically significantly lower than in healthy population. The best predictors of appearance and progression of glaucomatous disease are: AvgThic, RNFL thickness in quadrants: S,I,N; RNFL:Smax, Savg, Iavg; as well as PNO: RimArea, RimVol, DiscArea, CupAear, C/DHorRat, C/DVertRat, C/DAreaRat. ROC curve has shown that the following parameters are bad markers for progression of the disease: RNFL thickness in quadrant T, Imax and CupVol. Conclusion: Determination of parameters of optic nerve head and peripapillar RNFL in patients with glaucoma using optical coherent tomography represents the method that distinguishes the patients with preperimetric glaucoma from healthy subjects. It particularly points the sectors, quadrants and parameters that are the most sensitive to glaucomatous disease and that first become pathological when disease appears. It also indicates the difference between certain levels of glaucomatous disease. In this way safe and early diagnosis of glaucoma is provided, as well as adequate therapy and better prognosis in patients with POAG.</p>

This thesis deals with practical solutions of software for retinal images digital processing. The theoretic part describes human eye and retinal anatomy and also glaucoma disease. It is also focused on description of method for retinal nerve fiber layer enhancement and analysis. These enhancement are then used for designing of automated image processing. One chapter is devoted to detection and analysis of retinal nerve fibers layer. The practical part includes the user manual for application Image Blockz, which was established within this thesis. Further practical part contains the programmer's manual describing the basic structure of the program and its possible extensions.

<p>Cilj ovog istraživanja je bio da se utvrdi da li postoji razlika u debljini makule kod pacijenata sa glaukomom otvorenog ugla (POAG) u odnosu na zdravu populaciju i u zavisnosti od stepena progresije bolesti, kao i da se utvrdi da li postoji povezanost između promene debljine makule i stepena o&scaron;tećenja vidnog polja i debljine peripapilarnog sloja nervnih vlakana u zavisnosti od stepena progresije bolesti. Materijal i metode: U ovu kliničku prospektivnu studiju je uključeno 186 pacijenata. Na osnovu kliničkog nalaza formirane su tri grupe. Prva grupa (kontrolna &ndash; grupa zdravih): 68 pacijenata bez očnih oboljenja, sa najboljom korigovanom vidnom o&scaron;trinom &ge; 0.9, intraokularnim pritiskom (IOP) &le; 21 mmHg, normalnim odnosom ekskavacije i povr&scaron;ine glave vidnog živca i normalnim nalazom vidnog polja. Druga grupa (rani glaukom): 78 pacijenata sa klinički dijagnostikovanim primarnim glaukomom otvorenog ugla (sa karakterističnim o&scaron;tećenjem glave vidnog živca i sloja nervnih vlakana retine i kod kojih je srednja vrednost devijacije standardne automatske perimetrije MD &gt; -6 dB, prema Hodap klasifikaciji), bez drugih očnih ili sistemskih oboljenja, koja bi imala uticaj na nastanak glaukoma i sa najboljom korigovanom vidnom o&scaron;trinom &ge; 0.5. Treća grupa (glaukom srednjeg stepena): 40 pacijenata sa klinički dijagnostikovanim primarnim glaukomom otvorenog ugla (sa karakterističnim o&scaron;tećenjem glave vidnog živca i sloja nervnih vlakana retine i kod kojih je srednja vrednost devijacije standardne automatske perimetrije -6 dB &gt; MD &gt; -12 dB, prema Hodap klasifikaciji), bez drugih očnih ili sistemskih oboljenja, koja bi imala uticaj na nastanak glaukoma i sa najboljom korigovanom vidnom o&scaron;trinom &ge; 0.5. Svim pacijentima je bio urađen kompletan oftalmolo&scaron;ki pregled, kompjuterizovano vidno polje (Humphrey Field Analyzer, Carl Zeiss Meditec, Jena, Germany, SITA Standard, test C 24-2) i optička koherentna tomografija sloja nervnih vlakana peripapilarno i u predelu makule (SOCT Copernicus HR, Optopol Tech. SA, Zawiercie, Poland). Rezultati: Perifovea i parafovea, pokazuju statistički značajno smanjenje debljine i zapremine sloja nervnih vlakana u odnosu na stepen progresije glaukoma otvorenog ugla, pri čemu je ono nagla&scaron;enije u perifovei (p&lt;0,05). U svim segmentima makule (TPeriF, IPeriF, SPeriF, NPeriF, TParaF, SParaF, IParaF i NParaF) dolazi do smanjenja debljine i zapremine sloja nervnih vlakana sa progresijom bolesti (p&lt;0,05). Segmenti makule TPeriF, IPeriF, a potom i SPeriF, prema navedenom redosledu, predstavljaju segmente sa najvećim potencijalom za predikciju ranih glaukomskih o&scaron;tećenja s obzirom na uočeno najveće smanjenje debljine i zapremine nervnih vlakana (p&lt;0,05). Segmenti makule SParaF i NParaF predstavljaju segmente sa najvećim potencijalom za predikciju napredovanja glaukomskih o&scaron;tećenja srednjeg stepena s obzirom na uočeno najveće smanjenje debljine i zapremine nervnih vlakana (p&lt;0,05). Debljina RNFL glave vidnog živca se statistički značajno smanjuje sa progresijom bolesti u svim posmatranim segmentima (p&lt;0,05). Međusobni odnos između grupe zdravih i grupe pacijenata sa ranim glaukomom ukazuje da je statistički značajno smanjenje debljine RNFL prisutno u svim segmentima osim u segmentima P3 i P4 (p&gt;0,05). Merenja debljine RNFL u segmentu P6 imaju najbolji potencijal za predikciju ranog glaukoma s obzirom na najizraženije smanjenje debljine nervnih vlakana upravo u ovom segmentu (p&lt;0,05). Merenja debljine RNFL u segmentu P1 ima najbolji potencijal za predikciju dalje progresije bolesti. Debljina sloja nervnih vlakana makule srazmerna je smanjenju debljine RNFL na glavi vidnog živca, pri čemu je ona uočljivija na nivou segmenata koji su okarakterisani kao dobri prediktori za nastanak, odnosno progresiju bolesti (P6 sa IPeriF i TPeriF, odnosno P1 sa SPeriF), &scaron;to dodatno nagla&scaron;ava njihovu važnost u dijagnostici glaukoma otvorenog ugla. Debljina makule kod pacijenata sa glaukomom otvorenog ugla je opisana umerenom do dobrom povezano&scaron;ću sa stepenom o&scaron;tećenja vidnog polja, pri čemu je ona najjača kod TPeriF, IPeriF i SPeriF segmenata i srazmerna je stepenu o&scaron;tećenja vidnog polja. Koeficijenti korelacije između vrednosti srednje devijacije vidnog polja i debljine RNFL, odnosno&nbsp; sloja nervnih vlakana makule, pokazuju snažniju povezanost u odnosu na parametre dobijenog smanjenja debljine nervnih vlakana u makuli, &scaron;to otvara mogućnost za dalja istraživanja. Segmenti glave vidnog živca i makule, koji su pokazali najbolju diskriminaciju u smislu predikcije nastanka POAGa, kao i oni koji sugeri&scaron;u na njegovu progresiju, sme&scaron;teni su na lokacijama koje su međusobno povezane opisanim prirodnim tokom nervnih vlakana.&nbsp; Zaključak: Optička koherentna tomografija makule je važna pomoćna metoda u dijagnostici glaukoma kojom je moguće izdvojiti pacijente sa ranim glaukomom u odnosu na zdravu populaciju, odnosno utvrditi progresiju glaukoma otvorenog ugla.</p> / <p>All patients underwent complete ophthalmologic examination, SAP (Humphrey Field Analyzer, Carl Zeiss Meditec, Jena, Germany, SITA Standard, test C 24-2) and optical coherent tomography scans of RNFL and macula (SOCT Copernicus HR, Optopol Tech. SA, Zawiercie, Poland). Results: Perifoveal and parafoveal nerve fiber layer have shown significant reduction of thickness and volume compared to stage of POAG progression, where perifovea showed higher significance (p&lt;0,05). All macular segments (TPeriF, IPeriF, SPeriF, NPeriF, TParaF, SParaF, IParaF i NParaF) showed reduction in thickness and volume compared to disease progression (p&lt;0,05). Macular segments TPeriF, IPeriF, as well as SPeriF, represent segments with highest potential to predict early glaucomatous damage according to the most significant reduction of nerve fiber layer thickness and volume (p&lt;0,05). Macular segments SParaF and NParaF represent segments with highest potential to predict progression of POAG according to the most significant reduction of nerve fiber layer thickness and volume (p&lt;0,05). Optic nerve head (ONH) RNFL thickness showed reduction compared to POAG progression in all segments (p&lt;0,05). All ONH segments except P3 and P4 showed significant reduction of RNFL comparing control group to early glaucoma group patients (p&gt;0,05). ONH segment P6 was found to be the highly specific for early glaucoma prediction according to the most significant reduction of RNFL thickness (p&lt;0,05), while segment P1 was found to have highest potential for POAG progression. Macular nerve fiber layer thickness reduction follows ONH RNFL thickness reduction and there is mutual relation between both macular and ONH segments (P6 to IPeriF and TPeriF, P1 to SPeriF) with highest specificity for early defects and POAG progression. It was shown that macular thickness changes have moderate to good correlation with visual filed changes and it was highest in TPeriF, IPeriF and SPeriF segments. This correlation was found to be higher in macula then in ONH RNFL thickness changes, compared to visual field changes. Both macular and ONH RNFL segments, which were found to have highest specificity to POAG prediction and progression, are located in areas which mutually connect following natural course of nerve fiber layer between them. Conclusion: Optical coherence tomography of macula represents important ancillary method in POAG diagnosis and follow up, allowing to differentiate between early glaucoma patients and healthy individuals, as well as to determine progression of glaucomatous disease.</p>

Alterações no aspecto do disco óptico e da camada de fibras nervosas da retina (CFN) freqüentemente precedem o aparecimento de defeitos de campo visual no glaucoma, o que faz com que a avaliação destas estruturas seja essencial para o diagnóstico precoce e prevenção da perda visual nesta doença. A polarimetria de varredura a laser (GDx VCC), a oftalmoscopia confocal de varredura a laser (HRT II [Heidelberg Retina Tomograph]) e a tomografia de coerência óptica (Stratus OCT) são tecnologias que permitem a avaliação objetiva e quantitativa do disco óptico e da CFN. No presente estudo, estas tecnologias foram comparadas em sua habilidade para diferenciar pacientes glaucomatosos de indivíduos normais. Pacientes com glaucoma foram selecionados com base na presença de defeitos reprodutíveis de campo visual na perimetria acromática automatizada (glaucoma perimétrico), ou com base na evidência documentada de progressão do dano glaucomatoso ao disco óptico, sem presença de defeitos de campo visual (glaucoma pré-perimétrico). Indivíduos normais apresentaram campos visuais e exame clínico dentro da normalidade. Todos os indivíduos foram submetidos a exames com o GDx VCC, HRT II, Stratus OCT e campo visual dentro de um período de três meses. Diversas medidas foram utilizadas para avaliação da acurácia diagnóstica, incluindo áreas sob as curvas receiver operating characteristic (AROC), sensibilidades para especificidades fixas, e razões de probabilidade. Modelos estatísticos foram utilizados para avaliação da influência da severidade do glaucoma e tamanho do disco óptico na performance diagnóstica dos diferentes instrumentos. Um olho de cada indivíduo foi utilizado para análise. Dos 258 sujeitos inicialmente avaliados, 33 (13%) foram posteriormente excluídos por apresentarem imagens de baixa qualidade em pelo menos um dos aparelhos, restando 225 indivíduos (133 glaucomatosos e 92 normais) para análise. Na comparação entre os parâmetros de cada instrumento com maiores valores de AROC, o parâmetro do GDx VCC, Nerve Fiber Indicator (NFI; AROC = 0,91), e o parâmetro do Stratus OCT, Espessura Média (AROC = 0,90), apresentaram áreas sob as curvas ROC significativamente superiores à do parâmetro do HRT II, função discriminante de Bathija (AROC = 0,84). A severidade do defeito de campo visual exerceu influência significativa sob a acurácia diagnóstica dos três instrumentos, com melhora no poder diagnóstico em casos mais avançados da doença. Para o GDx VCC e Stratus OCT, o aumento no tamanho do disco óptico foi associado à diminuição na sensibilidade para detecção do glaucoma; enquanto que, para o HRT II, diminuição no tamanho do disco óptico foi associada à diminuição na sensibilidade. Razões de probabilidade para resultados anormais nas xxv classificações finais de cada instrumento foram associadas a grandes efeitos de mudança na probabilidade pós-teste em relação à probabilidade préteste, sugerindo que o encontro de um resultado anormal em qualquer um destes testes, durante a avaliação de um paciente com suspeita de glaucoma, tem impacto significativo em aumentar a probabilidade de que a doença esteja presente. Além disso, os resultados obtidos na avaliação de pacientes com glaucoma pré-perimétrico sugerem que todos os três instrumentos sejam capazes de detectar alterações estruturais precoces no glaucoma, antes do aparecimento de defeitos de campo visual na perimetria acromática / Changes in the structural appearance of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) have been reported to precede the development of visual field loss in glaucoma. Detection of ONH and RNFL damage is therefore crucial for early diagnosis of glaucoma and prevention of functional loss from the disease. Scanning laser polarimetry (GDx VCC), confocal scanning laser ophthalmoscopy (HRT II [Heidelberg Retina Tomograph]) and optical coherence tomography (Stratus OCT) are different technologies capable of providing objective and quantitative information related to these structures. The purpose of the present study was to compare, in a single population, the diagnostic abilities of these technologies in the discrimination of glaucomatous patients from healthy subjects. Glaucoma patients were selected based on the presence of repeatable visual field defects, as identified by standard automated perimetry (perimetric glaucoma), or documented evidence of progressive damage to the optic disc, in the absence of detectable visual field loss (preperimetric glaucoma). Normal subjects had normal visual fields and normal clinical examination. All subjects underwent imaging with the GDx VCC, HRT II and Stratus OCT within a 3-month period. Several measures were used for evaluation of diagnostic accuracy, including the area under the receiver operating characteristic curve (AROC), sensitivities at fixed specifities, and likelihood ratios. Statistical models were used to evaluate the influence of glaucoma severity and optic disc size on the diagnostic performance of the different instruments. One eye of each individual was randomly selected for statistical analysis. From an initial group of 258 eligible subjects, 33 (13%) had images of unacceptable quality, leaving 133 glaucoma patients and 92 healthy subjects for further analysis. In the comparison of the parameters with highest values of AROC from each instrument, the GDx VCC Nerve Fiber Indicator (AROC = 0.91) and the Stratus OCT Average Thickness (AROC = 0.90) perfomed significanlty better than the HRT II Bathija discriminant function (AROC = 0.84). For all instruments, the diagnostic accuracy increased with increasing severity of visual field defects. For the GDx VCC and Stratus OCT parameters, an increase in the size of the optic disc was related to a decrease in the sensitivity for glaucoma detection. An opposite effect was observed with the HRT II: a decrease in the size of the optic disc was related to a decrease in the sensitivity for glaucoma diagnosis. Abnormal results for each of the instruments were associated with strong positive likelihood ratios, indicating a large change from prestest to posttest probability of glaucoma. These results suggest that the finding of an abnormal result in any of these tests, when assessing a patient suspect of having glaucoma, would substantially raise the probability of disease. Results of the evaluation of patients with preperimetric glaucoma also suggest that all three instruments are able to detect early glaucomatous structural damage in the absence of visual field loss

Pacientes com compressão quiasmática apresentam perda das fibras nervosas da retina nasal que decussam no quiasma óptico. Por conseguinte, ocorre perda das fibras nervosas, predominantemente, no setor nasal e temporal do disco óptico, que se manifesta por atrofia em banda do nervo óptico ao exame oftalmoscópico e hemianopsia temporal ao exame de campo visual. Trabalhos anteriores mostraram que o tomógrafo de coerência óptica é capaz de diferenciar pacientes com atrofia em banda do nervo óptico associada à hemianopsia temporal completa de indivíduos normais através da análise da camada de fibras nervosas peripapilar. Estudos em glaucoma têm sugerido que a avaliação da espessura macular poderia ser útil na quantificação da perda neural como um método alternativo ou complementar ao estudo da camada de fibras nervosas da retina. No presente estudo, a espessura macular e da camada de fibras nervosas foram avaliadas pelo tomógrafo de coerência óptica em pacientes com atrofia em banda do nervo óptico e graus variados de hemianopsia temporal. O desempenho dos parâmetros maculares para detecção da atrofia em banda do nervo óptico foi avaliado pela área sob a curva ROC (AROC) e sensibilidades para especificidades fixas e os resultados foram comparados aos parâmetros da camada de fibras nervosas peripapilar. Para identificar os parâmetros do Stratus OCT que apresentaram melhor desempenho para diferenciar pacientes com AB do nervo óptico de indivíduos normais, modelos de regressão logística foram utilizados. A correlação estrutura-função foi realizada entre o grau do defeito temporal e os valores de espessura macular e da camada de fibras peripapilar através do coeficiente de correlação de Spearman. A categorização diagnóstica dos parâmetros da camada de fibras nervosas através do banco de dados normativos foi avaliada pelos valores de sensibilidade e especificidade calculados pelo teste exato de Fisher. Quarenta e quatro olhos com atrofia em banda e 47 olhos normais foram avaliados no estudo. Entre os parâmetros maculares, os parâmetros da retina nasal apresentaram melhor desempenho para detectar atrofia em banda do nervo óptico comparados aos parâmetros da retina temporal. Não houve diferença significante (p=0,32) entre as áreas sob a curva ROC do melhor parâmetro macular (AROC=0,97) e do melhor parâmetro da camada de fibras nervosas retiniana (AROC=0,99). Na avaliação da correlação estrutura-função, os parâmetros da retina nasal apresentaram maior correlação com o defeito campimétrico comparados aos parâmetros da camada de fibras nervosas da retinal. Entre os parâmetros maculares, a espessura nasal média apresentou a maior correlação (rs=0,618). Entre os parâmetros da camada de fibras nervosas da retina, a espessura média apresentou a maior correlação (rs=0,479). Os parâmetros espessura média, espessura nasal e espessura temporal da camada de fibras nervosas da retina apresentaram melhor desempenho diagnóstico baseado na categorização diagnóstica do banco de dados normativos. Os resultados obtidos no estudo mostraram que os parâmetros maculares discriminam olhos com atrofia em banda do nervo óptico em pacientes com graus variados de defeito temporal. Além disso, os parâmetros da retina nasal podem colaborar com o exame perimétrico e os parâmetros da camada de fibras nervosas para o seguimento dos pacientes com compressão quiasmática. / Patients with chiasmal compression present damage of crossed fibers of nasal retina. Therefore, retinal nerve fiber layer loss occurs predominantly on the nasal and temporal sides of the optic disc, a pattern that can be identified on ophthalmoscopy as band atrophy of the optic nerve and on visual field as temporal hemianopia. Previous studies have been demonstrated that optical coherence tomography is able to detect retinal nerve fiber layer loss in patients with lesions of the optic chiasm and complete temporal hemianopia. Studies in glaucoma have been suggested that macular thickness measurements could be useful in quantification of optical nerve axonal loss as alternative or complement method to evaluate the retinal nerve fiber layer. The purpose of the present study was to compare macular thickness and retinal nerve fiber thickness measurements in patients with band atrophy of the optic nerve and different severities of visual field defect using optical coherence tomography. Area under the receiver operating characteristic curve (AROC) and sensitivities at fixed specificities were performed for evaluation of diagnostic accuracy of macular and retinal nerve fiber layer parameters. To identify the best optical coherence tomography measurements to differentiate band atrophy of the optic nerve patients from normal individuals, logistic regression models were performed. Association between optical coherence tomography parameters and temporal field defect were examined by Spearman coefficient of correlation. Fisher\'s exact test was performed to evaluate diagnostic ability of retinal nerve fiber parameters by optical coherence tomography in eyes with band atrophy using comparison with its internal normative database. A total of 44 eyes with band atrophy of the optic nerve and 47 normal eyes were studied. Among macular parameters, nasal retina measurements showed diagnostic accuracy better than temporal retina measurements. No statistically significant difference (p=0.32) was found between areas under ROC curve for the best macular parameter (AROC=0.97) and the best retinal nerve fiber layer parameter (AROC=0.99). Nasal retina parameters correlations were higher than retinal nerve fiber parameters. The highest correlation was observed for the mean nasal thickness (rs=0.618) for macular parameters. In retinal nerve fiber parameters, the highest correlation was observed for the average thickness (rs=0.479). In evaluation of diagnostic ability of normative database, the average thickness parameter demonstrated the highest sensitivity for detection of abnormalities in eyes with band atrophy, followed by the parameters related to the nasal and temporal quadrants. These results suggest that macular thickness measurements discriminate eyes with band atrophy of the optic nerve with different severities of temporal field defect. Results also suggest that nasal retina thickness measurements could potentially be used to evaluate retinal ganglion cell loss in patients with chiasmal compression.

OBJETIVO: Avaliar a capacidade do potencial visual evocado multifocal (PEV-mf) em diferenciar pacientes portadores de hemianopsia temporal de controles normais e avaliar a correlação entre o PEV-mf, o campo visual (CV) realizado com a perimetria automatizada e a tomografia de coerência óptica de domínio fourier (TCO-dF). MÉTODOS: Vinte sete olhos de 21 pacientes com defeito de campo visual temporal secundário a compressão quiasmática e 43 olhos de 23 controles normais foram submetidos aos exames PEV-mf, CV e TCO-dF (3D OCT-1000®, Topcon) da mácula e da camada de fibras nervosas da retina (CFNR). Foi calculada a média das respostas do PEV-mf global, do PEV-mf central e a média de espessura do TCO-dF da mácula para cada quadrante e para cada hemicampo, enquanto a espessura da CFNR foi dividida em 12 setores ao redor do nervo óptico. A perda de CV foi calculada para os quatro quadrantes e para os hemicampos temporal e nasal no CV 24-2 e CV 10-2. Os dois grupos foram comparados utilizando equações de estimativas generalizadas (GEE) e as correlações entre o PEV-mf, CV e o TCO-dF foram calculadas. RESULTADOS: As médias das amplitude P1 e N2 do PEV-mf global e central para os hemicampos e os quadrantes temporais foram significativamente menores nos pacientes que nos controles (p < 0.004). Não houve diferença estatística entre os grupos para os parâmetros de amplitudes do PEV-mf nos setores nasais. Não houve diferença estatística nas médias das latências do PEV-mf global e central entre os pacientes e os controles normais. Foi encontrada correlação moderada, estatisticamente significativa, entre os parâmetros de amplitudes temporais do PEV-mf - global e central com a perda de CV 24-2 e 10-2 temporal, assim como com as medidas de espessura macular e da espessura CFNR na TCO-dF. CONCLUSÕES: As médias das amplitudes do PEV-mf foram capazes de diferenciar olhos de pacientes com hemianopsia dos controles normais e apresentaram correlação significativa com os dados obtidos pela perimetria automatizada e pelo TCO-dF. Estes dados sugerem que o PEV-mf global e central podem ser utilizados na detecção de anormalidades do campo visual em pacientes portadores de compressão quiasmática / PURPOSE: To evaluate the ability of multifocal visual evoked potential (mfVEP) to differentiate patients with temporal hemianopia due to chiasmal compression from normal controls. To assess the relationship between mfVEP, standard automated perimetry (SAP) and fourier domain-optical coherence tomography (fd-OCT). METHODS: Twenty-seven eyes of 21 patients with permanent temporal visual field (VF) defects from chiasmal compression and 43 eyes of 23 healthy controls underwent mfVEP, SAP and fd-OCT (3D OCT-1000®, Topcon) macular and peripapillary retinal nerve fiber layer (RNFL) measurements. It was averaged the responses for global mfVEP, central mfVEP and fd-OCT macular measurements were averaged in quadrants and halves, while peripapillary RNFL thickness was averaged in 12 sectors around the disc. VF loss was estimated in four quadrants and each half of 24-2 and 10-2 strategy test points. The two groups were compared using generalized estimated equations (GEE). Correlations between mfVEP, VF and fd-OCT findings were verified. RESULTS: Global and central mfVEP P1 and N2 amplitude parameters of temporal measurements were significantly smaller in patients than controls (p < 0.004). No significant differences were observed between the groups with respect to mfVEP amplitude parameters from the nasal measurements. No significant differences were observed in global and central mfVEP latency parameters for all averaged measurements between patients and healthy controls. A significant moderate correlation was found between global and central mfVEP amplitude parameters of temporal measurements and temporal VF 24-2 and 10-2 loss as well as with corresponding fd-OCT macular and RNFL thickness measurements. CONCLUSIONS: mfVEP amplitude parameters were able to differentiate eyes with temporal hemianopia from controls and were significant correlated with VF and fd-OCT findings. These data suggest that it is a useful technology for detecting visual abnormalities in patients with chiasmal compression

Objetivos: Analisar o potencial da oftalmoscopia confocal de varredura a laser, através do Heidelberg Retina Tomograph (HRT), para predizer o risco de progressão em pacientes com suspeita de glaucoma. Comparar os resultados obtidos com o índice de probabilidade de glaucoma (GPS) do HRT aos resultados da análise de regressão de Moorfields (ARM), dos parâmetros morfométricos e da avaliação das fotografias estereoscópicas. Métodos: Uma coorte foi selecionada com 223 pacientes com suspeita de glaucoma, que foram seguidos por um período médio de 64,9 ± 37,3 meses. A suspeita de glaucoma baseou-se na aparência do disco óptico e/ou na pressão intraocular elevada (> 21 mmHg). Todos os participantes apresentavam dois exames de campo visual normais ao entrar no estudo. Conceituou-se progressão como o desenvolvimento de um defeito confirmado de campo visual ou deterioração do disco óptico na avaliação seriada das estereofotografias. A associação entre os resultados do HRT na época do início do acompanhamento e a progressão para glaucoma foi investigada através de modelos de regressão do tipo Cox. Usou-se o C-index para a comparação entre os modelos com os diversos parâmetros do HRT, isolados ou ajustados para os outros já conhecidos fatores de risco para progressão (idade, espessura corneana, pressão intraocular e pattern standard deviation PSD). Resultados: No período do estudo, 46 pacientes (21%) apresentaram progressão. Na análise multivariada, o GPS, a ARM e diversos parâmetros morfométricos foram preditivos para progressão, assim como a avaliação subjetiva das estereofotografias. Cada GPS 0,1 maior foi associado com um aumento de 23% no risco de progressão (C-index de 0,69). Os resultados anormais nas classificações finais do GPS e da ARM foram associados a aumentos de 3 e 2 vezes no risco de progressão, respectivamente (C-indexes de 0,70 e 0,68, respectivamente). O parâmetro com o melhor C-index foi a área seccional tranversa da camada de fibras nervosas (0,72). Uma área 0,3 mm2 menor foi associada a um risco 62% maior de progressão. A comparação do valor preditivo entre os modelos com o GPS e com a avaliação subjetiva das estereofotografias foi similar (C-indexes de 0,69 e 0,68, respectivamente). Conclusão: Nesse estudo observamos que as análises objetivas do disco óptico e da região peripapilar obtidas com o HRT contribuíram na avaliação do risco de progressão em pacientes com suspeita de glaucoma. O GPS mostrou-se tão eficaz quanto os parâmetros morfométricos e a análise de regressão de Moorfields, e a comparação do desempenho dos modelos contendo a avaliação subjetiva das estereofotografias e aqueles contendo a avaliação objetiva pelo GPS não mostrou diferenças significativas / Purpose: To evaluate the ability of baseline confocal scanning laser ophthalmoscopy, using the Heidelberg Retina Tomograph (HRT), in predicting the development of progression in patients suspected of having glaucoma. In addition, the study also aimed to compare the predictive abilities of the glaucoma probability score (GPS) with those of the Moorfields regression analysis (MRA) and stereometric parameters, and to compare the performance of the HRT with that of subjective evaluation of optic disc stereophotographs. Methods: This longitudinal study included a cohort of 223 eyes suspected of having glaucoma, which were followed for an average of 64.9 ± 37.3 months. Included suspects had a suspicious appearance of the optic disc and/or elevated intraocular pressure, but normal visual fields. Progression was defined as the development of either repeatable abnormal visual fields or glaucomatous structural deterioration in the appearance of the optic disc during the study period. The association between baseline HRT parameters and progression was investigated by Cox regression models. The comparison between models with HRT parameters, individually or combined with other known risk factors (age, central corneal thickness, pattern standard deviation and intraocular pressure), performed by comparing their C-indexes. Results: Forty-six (21%) eyes converted during the study period. In multivariable models, the GPS, the MRA, and the stereometric parameters were all predictive of progression. A GPS 0.1 larger was associated with an increase of 23% in the risk of progression (C-index of 0.69). Abnormal final classifications for the GPS or the MRA were associated with a three-fold and two-fold increase in the risk of progression, respectively (with C-indexes of 0.70 and 0.68, respectively). The parameter with the best C-index was the nerve fiber layer cross-sectional area (0.72). An area 0.3 mm2 smaller was associated with a 62% higher risk of an individual progress. The comparison between models with the HRT parameters and those with the subjective stereophotograph evaluation had similar results (C-indexes of 0.69 and 0.68, respectively). Conclusion: In this study, we were able to show that the objective structural assessment of the optic disc and peripapillary area obtained with the HRT was significantly predictive for progression in suspected individuals. The GPS was as predictive as the other HRT parameters, and no significant differences were observed between models with the GPS and those with the subjective assessment of the stereophotographs.