Neuromyelitis optica (NMO) is a central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by acute myelitis (AM) and optic neuritis (ON), especially clinically severe longitudinally extensive transverse myelitis (LETM) and simultaneous bilateral ON. Patients with recurrent AM especially LETM without ON, and patients with recurrent ON without AM may have disorders belonging to the spectrum of NMO, neuromyelitis optica spectrum disorders (NMOSD). NMO is likely autoimmune in nature as a significant proportion of patients are seropositive for aquaporin-4 (AQP4) autoantibodies. I studied the clinical features of local Chinese NMOSD patients and their AQP4 autoantibodies seropositivity rates of by indirect immunofluorescence using tissue slides containing primate cerebellum (tissued-based immunofluorescence assay) in patients with 1) NMO, 2) classical multiple sclerosis (CMS), 3) acute disseminated encephalomyelitis (ADEM), 4) single attack or relapsing AM, 5) single attack or relapsing ON, and 6) other neurological disorders. The results showed that NMOSD are severe CNS IDD affecting patients with a wide range of onset ages. Chinese NMOSD patients predominantly have relapsing NMO and relapsing LETM with severe attack of LETM and/or ON. The six-year mortality rate of patients with NMO or relapsing myelitis with LETM was about 12%. Two-thirds of patients have poor neurological outcome at a mean duration of 6.0 years. The results confirmed that AQP4 autoantibodies are specific for NMOSD, and detection of AQP4 autoantibodies is clinically useful for early diagnosis of NMOSD and distinction from CMS. I proceeded to study a cell-based immunofluorescence assay using transfected human embryonic kidney cells overexpressing human AQP4 on cell membrane and found that cell-based assay has higher sensitivity than tissue-based assay in detection of AQP4 autoantibodies in NMO (78% versus 61%). As our NMOSD patients frequently presented clinically with severe brainstem symptoms and signs and lesions in brainstem and other brain regions on magnetic resonance imaging (MRI), I studied the clinical and neuroradiological characteristics of Chinese NMOSD patients with brain involvement. I found that 59% of NMOSD patients have clinical and/or radiological evidence of brain involvement. Importantly, brainstem is the most frequently affected brain region and 24% of NMOSD patients had clinical manifestation of brainstem encephalitis. I also studied the pathogenicity of AQP4 autoantibodies in the absence of complement activation by passive transfer of IgG isolated from sera of NMOSD patients into mice pretreated with complete Freund’s adjuvant (CFA, containing heat-killed mycobacterium tuberculosis) and pertussis toxin (PTx). I observed that pretreatment with CFA and PTx led to breach of BBB in mouse, and IgG isolated from sera of NMOSD patients seropositive for AQP4 autoantibodies led to asymptomatic loss of AQP4 in gray and white matter in mouse spinal cord without inflammatory cell infiltration, demyelination or astrocytic loss in the absence of complement activation (human IgG cannot activate mouse complements). My findings support that 1) AQP4 autoantibodies binding to astrocytic AQP4 per se can cause downregulation of AQP4 in the absence of complement activation, and 2) complement activation with resultant complement activation products play key roles in the inflammation, demyelination and astrocyte cytotoxicity in NMO. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Master of Medical Sciences

Background: Cryptococcal induced visual loss is common and increasingly becoming a debilitating consequence in survivors of cryptococcal meningitis (CM). Conflicting reports of the optic neuritis and papilloedema models of visual loss have delayed the introduction of effective interventional strategies for prevention and treatment of visual loss in CM. Qualitative and quantitative diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) of the optic nerves have proven useful in the examination of the microstructure of the optic nerve especially in optic neuritis. Its application has been extrapolated to other optic nerve disorders such as ischaemic optic neuropathy and glaucoma. The aim of this study is to elucidate the pathogenesis of cryptococcal-induced visual loss using diffusion imaging of the optic nerve as an investigational tool. Method: Full ethical approval was obtained from the Greys Hospital, Department of Health and University of KwaZulu Natal Ethics Committees. Reliable and reproducible optic nerve diffusion techniques were first developed and optimized on 29 healthy volunteers at Greys Hospital, Neurology and Radiology departments using a Philips 1.5 Tesla Gyroscan. Informed consent was also obtained from 95 patients suffering from CM (≥18 yrs. of age), 14 patients with papilloedema and 14 patients with optic neuritis from other causes, recruited from Greys and Edendale Hospitals. Patients underwent full neuro-ophthalmological assessments, CSF examination, haematological workup, CD4 count, (viral load for some), electrophysiological assessment of vision [Visual evoked potential (VEP) and Humphreys visual fields (HVF)], Magnetic Resonance Imaging (MRI) scan of the brain and orbits and DWI and DTI of the optic nerves. Results and Discussion: Visual loss is common in CM, occurring in 34.6-48%. Optic neuritis was uncommon as evidenced by a lack of signal change and lack of enhancement within the optic nerve in all patients scanned. The peri-optic CSF space was not dilated and the optic nerve diameter was not increased regardless of CSF pressure and visual status. Swollen optic discs occurred in only 25% of patients whereas raised intracranial pressure (> 20cmCSF) was demonstrated in 69-71% of patients. Therefore visual loss could not be explained by papilloedema alone. The VEP P100 latency was shown to be a useful screening test for subclinical optic nerve disease in CM, but HVF was not. The optic nerve diffusion imaging used was reliable and reproducible and produced diffusion parameters equivalent to other investigators in the field. Neither optic nerve movement nor the CSF signal was demonstrated to impact significantly on optic nerve diffusion parameters. Optic nerve diffusion imaging did not demonstrate similarities between CM and papilloedema or optic neuritis regardless of CSF pressure or vision. Conclusion: The rarity of optic neuritis in CM and the disparity between papilloedema and visual loss together with the lack of support from diffusion studies suggest a 3rd mechanism of visual loss viz. the optic nerve compartment syndrome. Good clinical support is provided by a case report for this hypothesis that shows re-opening of the peri-optic CSF space and return of the peri-optic CSF signal on MRI with lowering of intracranial pressure and antifungal treatment. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.

Despite that the RGC axons closely associated with astrocytes, the role of astrocytes in RGC regeneration was uncertain. In view of this, the effect of cultured adult astrocytes on RGC regeneration through an extensive ON lesion segment was studied. Adult ON astrocytes were prepared by sub-culturing of cells migrating out of ON explants. A small hole in the ON was punctured by 27G needle and about 0.5 to 1.0mul (1000 cells) cultured astrocytes was injected into the extensive ON lesion segment. We found that cultured adult astrocytes promoted significant RGC axon regeneration in the extensive ON lesion. / Finally, co-transplantation of intravitreal PN followed by transplantation of astrocytes into the extensive lesion has a synergistic effect on the regrowth of RGC axons, as indicated by the maximum distance achieved by regenerating axons and integrated intensity of staining of the CTB-labeled axons. Transplanatation of VPN+AST, VPN+NAST and NPN+AST as 3.9, 2.5 and l.9 times more potent in inducing regeneration than that of NPN+NAST as shown by integrated intensity measurement. However, co-transplantation of PN and astrocytes could not enhance RGC survival. (Abstract shortened by UMI.) / In this study, we have established an extensive lesion paradigm to study the behavior of injured retinal ganglion cell (RGC) axons after ON crush in adult golden hamster. We found that RGC axons regenerated in the extensive lesion for 406.8mum at 1 week post-crush to 1174.0mum at 4 weeks post-crush. RGC axons were able to regenerate the entire lesion segment but they terminated precisely at the interface between the lesion and the distal segment of the ON. Regrowing axons were intimately associated with astrocytes which repopulated the lesion segment. Repopulated oligodendrocytes were scattered in the lesion segment and myelin debris was significantly decreased in the lesion segment with time. / It is commonly believed that central nervous system (CNS) neurons are unable to regenerate after injury. Recently, there have been several lines of evidence showing that damaged CNS neurons can undergo axonal regeneration under appropriate conditions. Since the retina and optic nerve (ON) are regarded as part of the CNS, therefore, they are used as a model to study CNS regeneration. / Kong Wai Chi. / "July 2005." / Adviser: Y.P. Cho. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3616. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 96-115). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Orientador: Edi Lúcia Sartorato / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T22:58:29Z (GMT). No. of bitstreams: 1 Miranda_PauloMauriciodoAmorDivino_D.pdf: 3949549 bytes, checksum: 8cd1e0647087ac34cd2bc0ed5d096d0b (MD5) Previous issue date: 2014 / Resumo: A Neuropatia Óptica Hereditária de Leber (LHON) e a Atrofia Óptica Autossômica Dominante (ADOA ou OPA1) são doenças caracterizadas pela perda da visão bilateral, devido a uma degeneração do nervo óptico. Ambas as doenças apresentam também acuidade visual reduzida, discromatopsia, palidez do nervo óptico e escotoma central ou centrocecal. A LHON é causada por mutações no DNA mitocondrial (mtDNA), onde três dessas mutações representam 95% dos casos (mutações primárias principais G11778A, T14484C e G3460A) e as mutações subsequentes representam apenas 5% do total (mutações raras). A ADOA é causada por mutações (mais de 300) no gene nuclear OPA1. Embora os mecanismos moleculares precisos envolvidos no desenvolvimento das duas doenças ainda não são bem compreendidos, foi demonstrado que LHON e ADOA possuem um defeito comum de acoplamento da fosforilação oxidativa. Nesses dois casos, a hipótese é de que as mutações no mtDNA e no gene OPA1 afetariam a integridade mitocondrial, resultando em uma diminuição do fornecimento de energia para os neurônios do nervo óptico. É possível que no Brasil a presença e frequência das alterações da relacionadas à LHON e ADOA sejam diferentes das encontradas em outras partes do mundo. Por isso, o presente estudo teve como principais objetivos rastrear mutações e haplogrupos associadas à LHON e detectar mutações no gene OPA1 em pacientes brasileiros com hipótese diagnóstica de LHON e com Neuropatia Óptica de etiologia a esclarecer. Também foi objetivo otimizar o método de PCR Multiplex Alelo-Específico e padronizar as plataformas de alto rendimento TaqMan® OpenArray® e Iplex Gold/Maldi TOF MS para o rastreamento da LHON. Foram avaliados 101 pacientes, sendo 67 com hipótese diagnóstica de LHON e 34 com neuropatia óptica de etiologia a esclarecer. As mutações da LHON foram detectadas por meio de PCR-RFLP e PCR Multiplex Alelo-Específico. As mutações raras da LHON e do gene nuclear OPA1 (10 principais éxons) foram rastreadas por sequenciamento direto. Foram encontradas mutações da LHON em 36 casos (83.3% com a mutação G11778A e 16.7% com a mutação T14484C). Não foi encontrada a mutação G3460A. Também não foram encontradas mutações raras da LHON e nem mutações relacionadas à ADOA. Haplogrupos de origem africana (L1/L2 e L3) foram mais frequentes no estudo. Foi otimizado o método de PCR Multiplex Alelo-Específico e padronizadas as plataformas TaqMan® OpenArray® e Iplex Gold/Maldi TOF, os quais se mostraram reprodutivos, eficientes e eficazes. A análise molecular das mutações da LHON e do OPA1 foi importante para a confirmação do diagnóstico de 35% dos casos clínicos típicos de LHON e para a elucidação 35% casos de neuropatia óptica de etiologia a esclarecer / Abstract: The Leber Hereditary Optic Neuropathy (LHON) and Autosomal Dominant Optic Atrophy (ADOA) are diseases characterized by loss of vision in both eyes due a degeneration of the optic nerve. Both diseases also exhibit reduced visual acuity, dyschromatopsia, optic nerve and central scotoma or centrocecal. The LHON is caused by mutations in mitochondrial DNA (mtDNA), where three of these mutations account for 95% of cases (major primary mutations G11778A, T14484C and G3460A) and subsequent mutations account for only 5% of the total (rare mutations). The ADOA is caused by mutations (more than 300) in the nuclear gene OPA1. Although the precise molecular mechanisms involved in the development of the two diseases are not well understood, it was shown that LHON and ADOA have a common defect coupling of oxidative phosphorylation. In both cases, the hypothesis is that mutations in mtDNA and OPA1 gene affect mitochondrial integrity, resulting in a decrease in the supply of energy to the neurons of the optic nerve. It is possible that in Brazil the presence and frequency of changes related to LHON and ADOA be different from those found in other parts of the world. Therefore, the present study had two main objectives track haplogroups and mutations associated with LHON and detect mutations in the OPA1 gene in Brazilian patients with a diagnosis of LHON and optic neuropathy of unknown etiology. Another objective was to optimize the method of PCR Multiplex allele-specific and standardize platforms high throughput TaqMan® OpenArray® and Iplex Gold/Maldi TOF MS for screening of LHON. 101 patients were evaluated, 67 with a diagnosis of LHON and 34 with optic neuropathy of unknown etiology. LHON mutations were detected by PCR-RFLP and allele-specific multiplex PCR. Rare mutations of LHON and nuclear gene OPA1 (top 10 éxons) were screened by direct sequencing. LHON mutations were found in 36 cases (83.3% with the G11778A mutation and 16.7% with the T14484C mutation). Not the G3460A mutation. Nor rare mutations of LHON and ADOA or related mutations were found. Haplogroups of African origin (L1/L2 and L3) were more frequent in the study. The method of allele-specific multiplex PCR was optimized and standardized the TaqMan® OpenArray® and iPLEX Gold/Maldi TOF platforms which are shown reproductive, efficient and effective. Molecular analysis of mutations of LHON and ADOA was important to confirm the diagnosis of 35% of the typical clinical cases of LHON and to elucidate 35% cases of optic neuropathy of unknown etiology. Besides being useful also in the prognosis of each patient, for the phenotypic expression of the LHON and ADOA may vary with different genetic background in our population of individuals / Doutorado / Genetica Animal e Evolução / Doutor em Genetica e Biologia Molecular

<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>