Functional analysis of disease-causing NR2E3 mutations

Purpose:We analyzed the transcriptional activity of disease-causing NR2E3 mutant proteins in a heterologous system. NR2E3 belongs to the nuclear receptor superfamily of transcription factors, characterized by evolutionary-conserved DNA-binding (DBD) and ligand-binding (LBD) domains. NR2E3 acts in concert with the transcription factors CRX and NRL to repress cone-specific genes and activate rod-specific genes in rod photoreceptors. During development, NR2E3 is also required to suppress cone cell generation from retinal progenitor cells. In humans, mutations in NR2E3 have been associated with the recessively inherited enhanced short wavelength sensitive (S-) cone syndrome (ESCS), the Goldman-Favre syndrome, and, more recently, with autosomal dominant retinitis pigmentosa (adRP). Methods:The different NR2E3 mutants were generated by QuickChangeR mutagenesis and analyzed by transfection in heterologous HEK293T cells. Results:In transactivation assays in HEK293T cells, the adRP-linked p.G56R mutant protein exhibited a more severe effect both in activation of a rhodopsin promoter reporter construct and in repression of M-opsin promoter reporter construct, than the ESCS-linked R76Q, R76W, G88V, R97H, R104Q, R104W mutants of the DBD. In contrast, the ESCS-linked p.R311Q mutant of the LBD behaved like the NR2E3 wild-type protein in these assays. By co-expressing the corepressors atrophin-1 and -2, a differential repression of the M-opsin promoter was observed in presence of the p.R311Q, p.R385P and p.M407K. Interestingly, corepressor expression also affected the activity of CRX, but not NRL, in both rhodopsin and M-opsin transactivation assays. Conclusions:Taken together, these in vitro results suggest a distinct disease mechanism for the adRP-linked mutation, but open the possibility of different mechanisms for the development of ESCS that is clinically characterized by important phenotypic variations.

Modified Corneal Collagen Crosslinking (CXL) Reduces Corneal Edema and Diurnal Visual Fluctuations in Fuchs' Dystrophy

Purpose: Crosslinking of corneal collagen with riboflavin and ultraviolet-A irradiation (CXL) induces crosslinks within and between collagen fibers. CXL increases corneal biomechanical and biochemical stability and is currently used clinically to treat keratectasia. CXL also significantly reduces the stromal swelling capacity. We investigated whether a modified CXL treatment protocol would be beneficial in early Fuchs' dystrophy with various degrees of corneal edema and diurnal variations in visual acuity. Methods: CXL was performed as published previously with the following modification: in cases where the stroma was thicker than 450 µm after abrasion and 30 minutes of instillation of isoosmolar riboflavin solution, glycerol 70% solution was applied every 5 seconds for two minutes, and central corneal thickness (CCT) was measured using ultrasound pachymetry. Glycerol 70% solution was administered repeatedly until the target corneal thickness of 370-430 µm was reached. During irradiation, CCT was monitored by ultrasound pachymetry every five minutes and glycerol 70% solution was applied, if necessary. Results: Three eyes in two patients were treated using the modified CXL protocol. Representative case: a 50-year-old woman with Fuchs' dystrophy and a history of 3 years of diurnal visual fluctuations was referred to us in March 2008. Preoperative best spectacle-corrected visual acuity (BSCVA) was 20/50. We performed modified CXL in the left eye. At one month after CXL, Scheimpflug analysis of CCT showed a reduction of more than 100 µm, and the Corneal Thickness Spatial Profile (CTSP) and Percentage of Increase in Thickness (PIT) showed a regularization of the "flattening" typical for Fuchs' dystrophy. Accordingly, diurnal analysis of corneal thickness showed a distinct postoperative reduction in CCT at all time points measured. At one month after CXL, the patient reported a reduction of diurnal visual fluctuations and we measured an increase in BSCVA to 20/32. The patient showed stable topographical and visual acuity at the three months follow-up. Conclusions: We saw a distinct reduction in CCT, an improvement of the corneal thickness spatial profile (CTSP) and an increase in BSCVA at one month after treatment, which remained stable at the three months follow-up. Patients with early Fuchs' dystrophy and disturbing diurnal visual fluctuations represent a novel application for CXL. Although CXL may not prevent the outcome of the dystrophy, it may increase the patients' visual comfort until keratoplasty becomes necessary.

Point Mutations in the Monocarboxylate Transporter SLC16A12 Lead to Juvenile and Age-Related Cataract

Purpose: Previously we reported on a premature termination mutation in SLC16A12 that leads to dominant juvenile cataract and renal glucosuria. To assess the mutation rate and genotype-phenotype correlations of SLC16A12 in juvenile or age-related forms of cataract, we performed a mutation screen in cataract patients. Methods: Clinical data of approximately 660 patients were collected, genomic DNA was isolated and analyzed. Exons 3 to 8 including flanking intron sequences of SLC16A12 were PCR amplified and DNA sequence was determined. Selected mutations were tested by cell culture assays, in silico analysis and RT-PCR. Results: We found sequence alterations at a rate of approximately 1/75 patients. None of them was found in 360 control alleles. Alterations affect splice site and regulatory region but most mutations caused an amino acid substitution. The majority of the coding region mutations maps to trans-membrane domains. One mutation located to the 5'UTR. It affects translational efficiency of SLC16A12. In addition, we identified a cataract-predisposing SNP in the non-coding region that causes allele-specific splicing of the 5'UTR region. Conclusions: Altered translational efficiency of the solute carrier SLC16A12 and its allele-specific splicing strongly support a model of challenged homeostasis to cause various forms of cataract. In addition, the pathogenic property of the here reported sequence alterations is supported by the lack of known sequence variations within the coding region of SLC16A12. Due to the relatively high mutation rate, we suggest to include SLC16A12 in diagnostic cataract screening. Generally, our data recommend the assessment of regulatory sequences for diagnostic purposes.

Use of a short hPDE6b promoter for rod gene transfer in a model of severe retinal cystrophy, the Rd10 mouse

Purpose: Gene therapy of severe retinal dystrophies directly affecting photoreceptor is still a challenge in terms of clinical application. One of the main hurdles is to generate high transgene expression specifically in rods or cones. In the present study, we are investigating the possibility to drive hPDE6b expression in the Rd10 mouse retina using a specific sequence of the human PDE6b promoter. Methods: Two 5' flanking fragments of the human PDE6b gene: (-93 to +53 (146 bp) and -297 to +53 (350 bp, see Di Polo and Farber, 1995) were cloned in different plasmids in order to check their expression in vitro and in vivo. These elements drove the activity of either luciferase (pGL3 plasmids) or EGFP (AAV2/8 backbone). Then, an AAV2/8 vector carrying the PDE6b cDNA was tested with subretinal injections at P9 in the Rd10 eyes. Eye fundus, OCT, ERG recordings and histological investigations were performed to assess the efficacy of the gene transfer. Results: The short PDE6b promoter containing 146bp (-93 to +53) showed the highest activity in the Y-79 cells, as described previously (Di Polo and Farber, 1995). Subretinal administrations of AAV2/8-PDE6bpromoter-EGFP allowed a rapid expression specifically in rods and not in cones. The expression is faster than a vector containing the CMV promoter. The AAV2/8-PDE6bpromoter-PDE6b and the control vector were injected at P9 in the Rd10 mouse retina and investigated 5 weeks post-injection. Out of 14 eyes, 6 presented an increased rod sensitivity of about 300 fold, and increased a- and b-wave responses in ERG recordings. Flicker stimulations revealed that cones are also functional. OCT images and histological analyses revealed an increased ONL size in the injected area. The retina treated with the therapeutic vector presented 4-6 rows of photoreceptors with outersegments containing PDE6b. In the control eyes, only 2-4 rows of photoreceptors with almost no OS were observed . Conclusions: The 146 bp promoter sequence (-93 to + 53) is the shortest regulatory element described to date which allows to obtain efficient rod-specific expression in the context of somatic gene transfer. This first result is of great interest for AAV vector design in general allowing more space for the accommodation of transgenes of interest and good expression in rods. Moreover we showed the proof of principle of the efficacy of AAV2/8-PDE6bp-PDE6b vector in the Rd10 mouse model of severe photoreceptor degeneration without using neither AAV mutated capsids, nor self-complementary vectors.

Melastatin Expression in Ocular Melanocytic Proliferations

Purpose: Melastatin (MLSN-1) belongs to the transient receptor potential (TRP) superfamilly of calcium-permeable channels, and has been reported to be a melanocyte-specific gene. In human cutaneous melanoma, MLSN-1 mRNA expression displays a pattern of inverse correlation to disease free survival. We describe the patterns of MLSN-1 mRNA expression in conjunctival nevi, conjunctival melanoma, and uveal melanoma. Methods: In situ hybridization using two S35-labelled riboprobes for MLSN-1 was performed on formalin-fixed, paraffin-embedded tissues. A control probe for H4 histone was used to confirm mRNA integrity in these archival tissues. The 21 ocular melanocytic lesions studied included 5 conjunctival nevi, 6 conjunctival melanomas, and 10 enucleated eyes with uveal melanoma. The minimal requirement for interpretation of MLSN-1 mRNA loss was the presence of only background signal in a focus of at least 5 adjacent melanocytic cells. Results: Ubiquitous expression of MLSN-1 mRNA was found in conjunctival melanocytes in the non-lesional epithelium adjacent to the conjunctival melanocytic proliferations and in all 5 conjunctival nevi studied. Four different patterns of MLSN-1 mRNA expression were observed in conjunctival melanomas: one case showed complete preservation of MLSN-1 mRNA, two cases showed diffuse scattered loss of MLSN-1 mRNA, two cases showed focal clonal loss of MLSN-1 mRNA expression, and one case had no detected MLSN-1 mRNA. In uveal melanomas, MLSN-1 mRNA expression was partially preserved in two cases, lost by a clearly delimited subset of tumor cells (focal clonal loss) in four cases, and was not detectable in the entire tumor in four cases. MLSN-1 mRNA expression was also found in the normal iris, ciliary and choroidal melanocytes as well as in the retinal pigmented epithelium and in the inner nuclear layer of the retina. Conclusions: The patterns of MLSN-1 mRNA expression in the ocular melanocytic proliferations are similar to those reported in cutaneous melanocytic proliferations. In the conjunctiva, MLSN-1 mRNA expression appeared to correlate with tumor progression; all the benign conjunctival nevi had preserved expression of MLSN-1 mRNA and most of the conjunctival melanomas partial or complete loss of expression. In uveal melanoma, patterns of melastatin expression ranging from partial preservation to complete loss were found. Additional studies of a large number of ocular melanocytic proliferations may show a correlation with tumor progression and prognosis similar to that observed in cutaneous melanoma.

Establishment of a reliable laser-Induced Choroidal Neovascularization Animal Model

Purpose: Pathologic choroidal neovascularizations (CNV) are implicated in the wet form of age-related macular degeneration (ARMD). Abnormal vessel growth is also observed in disease when hypoxia and/or inflammation occur. Our goal is to establish a standard protocol of laser-induced CNV in mice that have different levels of pigmentation to identify the most reliable animal model.Methods: CNV was induced by 4 burns around the optic disk, using a green argon laser (100μm diameter spot size; 0,05 sec. duration) in C57/Bl6, DBA/1 and Balb/c to ascertain the efficacy of the method in function of retina pigmentation. Five different intensities were tested and Bruch's membrane disruption was identified by the appearance of a bubble at the site of photocoagulation. Fluorescein angiographies (FA) were undertaken 14 days post lesion and CNV area was quantified by immunohistochemistry on cryosections.Results: CNV retina area was related to spot intensity after laser injury. While 180mW and 200mW do not induce reliable CNV (respectively 27.85±0.35% and 29±1.67% of the retina surface), 260mW is required to induce 51,07±8.52% of CNV in C57/Bl6 mice. For the DBA/1 strain, less pigmented, 200mW was sufficient to induce 49.35±3.9% of CNV, indicating that lower intensity are required to induce CNV. Furthermore, an intensity of 180mW induced greater CNV (35.55±6.01%) than in C57/Bl6 mice. Nevertheless, laser did not induce reproducible 50% CNV in Balb/c albino mice for all intensities tested. Isolectin-B4 and GFAP stainings revealed neovessel formation and photoreceptor (PR) degeneration at the impact site. The presence of glia was observed throughout all the retinal layers and angiograms showed fluorescein leakage in pigmented mice.Conclusions: The establishment of a standard protocol to induce CNV and subsequent PR degeneration is of prime importance for the use of the laser-induced CNV model and will allow to evaluate the therapeutic potency of agents to prevent CNV and retinal degeneration.

7-10 -vuotias lapsi ortopantomografia- ja lateraalikallotutkimuksissa

Opinnäytetyömme tarkoituksena oli laatia kirjallinen potilasohje 7-10 -vuotiaille lapsille, jotka tulevat röntgeniin ortopantomografia- ja lateriaalikallotutkimuksiin. Teimme opinnäytetyömme yhteistyössä Haminan sairaalan röntgenin henkilökunnan kanssa, jossa tällaiselle ohjeelle oli tarvetta. Kerromme opinnäytetyömme kirjallisessa osiossa yleisesti lapsen kehityksestä, ortopantomografia- ja lateraalikallotutkimuksista, lasten säteilysuojelusta, kirjallisen ohjeen tekemisestä ja lapsen ohjaamisesta kirjallisen ohjeen avulla. Enemmin näistä aiheista syvennyimme lapsen kehitykseen, ohjaukseen ohjeen avulla ja kirjallisen ohjeen tekemiseen. Opinnäytetyötämme varten saimme taustatietoa aiheeseen liittyvästä kirjallisuudesta, oman alamme lehtien artikkeleista sekä Internetistä. Pystyimme myös hyödyntämään omaa kokemustamme ja tietojamme opinnäytetyömme teossa. Ohjeeseen tarvittavan kuvamateriaalin kuvasimme itse paikan päällä Haminan sairaalan röntgenissä. Ohjeen tavoitteena on vähentää lasten ennakkoluuloja ja pelkoja mainittuja tutkimuksia kohtaan. Siinä on valokuvia, jossa on mallina kohderyhmäämme kuuluva lapsi ja teksti on esitetty lyhyinä ja selkeinä kokonaisuuksina, jotta lapsi jaksaa lukea ohjeen mielenkiinnolla kokonaan läpi. Ohjeen avulla lapsen, ja miksei aikuisenkin, on helppo hahmottaa, mitä tutkimuksissa tapahtuu vaihe vaiheelta. Orientoitunut lapsi on yhteistyökykyinen ja tämän ansiosta röntgenhoitajan työ tutkimuksen aikana helpottuu. Ohjeen on tarkoitus olla helppolukuinen ja tarpeeksi selkeä lapsille. Sitä voi käyttää apuvälineenä lasten ohjauksessa ortopantomografia- ja lateraalikallotutkimuksiin.

Osteopaattisen hoidon vaikuttavuus niska- ja hartiaperäisissä kiputiloissa : arviointi NDI-mittarilla

Selvitimme opinnäytetyössämme osteopaattisen hoidon vaikuttavuutta niska- ja hartiaperäisissä kiputiloissa Neck Disability Index (NDI) -mittarilla arvioituna kokeellisessa tutkimusasetelmassa. Tutkimushenkilöt valittiin Stadian sosiaali- ja terveysalalle huhtikuussa 2006 lähetetyn sähköpostikutsun vastausten perusteella. Tutkimukseen osallistumisen valintakriteerejä olivat niska- tai hartiakipu, jännityspäänsärky sekä 18-40 vuoden ikä. Halukkaista valitsimme 12 tutkimushenkilön tutkimusjoukon. Lopullisissa tutkimustuloksissa on huomioitu 11 tutkimushenkilön tulokset. Artikulaatiotekniikoita käytettiin kaula- ja rintarangan fasettinivelten mobilisointiin. Pehmytkudostekniikoita käytettiin CES (cervical erector spinae)- ja DES (dorsal erector spinae) -alueiden esihoitona. Manipulaatiotekniikoilla hoidettiin rintarangan aliliikkuvia segmenttejä. MET-tekniikoilla pyrittiin vaikuttamaan CES-alueen lihasten tonukseen ja kaularangan kokonaisliikelaajuut een. Tutkimushenkilö täytti NDI-mittarin ennen ensimmäistä tutkimus- ja hoitokertaa sekä kolme päivää viimeisen hoitokerran jälkeen. NDI-mittareiden vastaukset pisteytettiin erillisiksi tuloksiksi ennen ja jälkeen hoitojen. Saatuja tuloksia vertailtiin keskenään yksittäisen tutkimushenkilön kohdalla. Tuloksia tarkasteltiin NDI-arvon prosentuaalisena muutoksena suhteessa alkutilanteeseen. NDI-mittarin osoittama niskahaitta-arvo laski yhdeksällä ja nousi kahdella tutkimushenkilöllä. Koko tutkimukseen osallistuneen ryhmän prosentuaalisen muutoksen keskiarvo oli -58,68 Tutkimustulosta voidaan pitää merkittävänä, mutta otannan ollessa näin pieni, emme pysty yleistämään tehtyjen hoitojen vaikuttavuutta. Tutkimuksen perusteella näyttäisi siltä, että DES-alueen lihaskivuista valitetaan vähän verrattuna saman alueen nikamatason löydöksiin. Löydösten pohjalta on mahdollista ajatella, että DES-alueen ylä- ja keskiosan segmentaariset dysfunktiot kompensoituvat CES-alueen lihaskipuin a. Sen vuoksi ehdotamme rintarangan käsittelyn olevan hyväksyttävä vaihtoehto kaularangan manipulaatiolle sen samankaltaisten vaikutusten takia. Tämä ajattelumalli on myös käypähoitosuositusten mukainen. Jatkotutkimuksia kyseisestä aiheesta tarvitaan. Ehdotuksenamme jatkotutkimusten tutkimusasetelmalle on hoitaa ainoastaan rintarangan alueen dysfunktioita ja seurata sen suoria vaikutuksia kaularangan alueelle.

Toistettavuus- ja validiteettitutkimus sekä seated flexion testi

Tämän opinnäytetyön tarkoituksena on tehdä toistettavuus- ja validiteettitutkimuksien tekeminen helpommaksi manuaalisen lääketieteen ihmisille. Manuaalisessa lääketieteessä käytettyjä testejä ja hoitomenetelmiä ei ole tutkittu tarpeeksi eikä niiden käytettävyyttä ole tieteellisesti todennettu. Työtä varten on käännetty FIMM:n (Kansainvälinen manuaalisen lääketieteen yhdistys) toistettavuus- ja validiteettitutkimusprotokolla. Sen avulla voi jokainen koulutettu manuaalisen hoitoalan ammattilainen tehdä toistettavuus- ja validiteettitutkimuksia kansainvälisesti julkaistaviksi. Protokollan mukaisesti tehdyt tutkimukset ovat vertailukelpoisia ja helposti toistettavia. Käännöksen tarkoituksena on tuoda tutkimusprotokolla tunnetuksi Suomessa. Tutkimusprotokollan myötä toivotaan manuaalisten hoitoalojen ammattilaisten tekevän kasvavassa määrin vastaavanlaisia tutkimuksia ammatillistumisen lisäämiseksi. FIMM:n protokollan mukaisesti toteutettiin kappatutkimus SI-nivelen liikkuvuutta testaavasta seated flexion testistä. Testistä ei ole aikaisemmin tehty toistettavuus- ja validiteettitutkimusta. Opinnäytetyössä esitellään seated flexion testin suorittamisen eri tapoja. Aikarajoituksista johtuen tutkimuksen kaikkia vaiheita ei suoritettu protokollan edellyttämällä tasolla. Testivaiheessa kappa-arvo jäi alle kliinisesti merkittävän 0,4 arvon. Alhaisen kappa-arvon takia ei voida osoittaa testin toistettavuutta ja validiteettia. Johtopäätöksenä tutkimuksesta voidaan todeta, että seated flexion testistä tarvitaan lisää vastaavanlaisia kappatutkimuksia.

Syvä ajatus : YleQ-radiokanavan ääni-imago Yleisradion brändin rakentajana

Tarkastelen opinnäytetyössäni Yleisradion brändin rakentamista YleQ-radiokanavalle tekemieni imagopuffien kautta. Brändin käsite ymmärretään monella eri tavalla. Opinnäytetyössäni olen kilpailevien määritelmien pohjalta rajannut brändin tarkoittamaan Yleisradion pyrkimystä vaikuttaa kuluttajien tunteisiin ja mielikuviin. Pyrin työssäni alan kirjallisuuden, YLEn itsensä laatimien brändi-, arvo- ja visiokirjelmien, julkisen mediakeskustelun sekä haastattelujen pohjalta hahmottelemaan hyvään brändiin vaikuttavat arvot ja tekijät. Tutkimuksessani tarkennan brändin tarkastelun YleQ-radiokanavaan ja arvioin, onnistuivatko tekemäni imagopuffit niille asetetuissa tavoitteissa. Tarkastelen Yleisradion brändityön komentotietä ja pohdin yksilön merkitystä yhtiön brändäyksen onnistumisessa. Pohdin myös brändityön suunnittelun merkitystä YleQ-kanavan lopettamispäätöksessä. YLEn itselleen laatimat arvot eivät tutkimukseni mukaan toteudu käytännössä ja siksi yhtiön brändi on haasteen edessä. Yhtiöllä olisi mielestäni kaksi tärkeää kehittämiskohtaa. Ensinnäkin yhtiön tulisi luottaa työntekijöihinsä ja ottaa rohkeasti vastaan heidän ajatuksiaan, jotta Yleisradion toiminnassa saataisiin esille kaikki mahdollinen luovuus ja intohimo. Yleisradion pitäisi myös rajata markkinointinsa viestit tarkemmin. Tämä parantaisi kuluttajan tiedonsaantia Yleisradion tarjoamista palveluista ja helpottaisi yhtiön yhtenäisen brändin rakentamista.

Päätoimittaja Pauli Burman 24/10 1969

Kirje 24.10.1969

Multi-layer amniotic membrane (MLAM) transplantation for non traumatic corneal perforations or descemetoceles

Purpose:To describe the indications, the surgical procedure and the clinical outcome of MLAM in the treatment of non traumatic corneal perforations and descemetoceles . Methods:A prospective, non comparative, interventional case series of eight consecutive patients (mean age 59 years old, 6 men and 2 women) with non traumatic corneal perforations or descemetoceles.The surgery consisted in a MLAM transplantation of a cryopreservated human amniotic membrane. The series included: three active herpetic keratitis, one rosacea, one perforation of an hydrops, one cicatricial pemphigoid, one perforation after an abcess in a corneal graft and one perforation after protonbeamtherapy. The clinical outcome included: the follow-up, the integrity of the eye, corneal epithelialization, inflammation and neovascularization, and the integration of the MLAM. Stromal thickness was followed precisely with the slit lamp. A corneal graft was performed at one patient after the MLAM, allowing microscopic investigation of the removed MLAM integrated in the cornea. Results:The mean follow-up was 8.78 months (range 3.57 to 30.17). Amniotic membrane transplantation was successful and reduced inflammation in 7 patients out of 8 ,after one procedure.One patient who presented a large herpetic keratitis epithelial defect with corneal anaesthesia had his MLAM dissolved after two weeks with an aqueous leakage. Epithelium healed within 3 weeks above 7 MLAM and remained stable at 3 months in 7 out of 8 patients. MLAM opacification gradually disappeared over a few months, however, stromal layers filling in the corneal perforations or above the descemetoceles remained stable. Conclusions:MLAM transplantation is a safe, effective and useful technique to cure non traumatic corneal perforations and descemetoceles. It can be performed in emergency despite the presence of an active inflammation or infection. By facilitating epithelialization, reducing inflammation and neovascularization, it allows corneal surface reconstruction in patients with persistent epithelial defects and corneal melting that usually ends in a perforation. For full visual rehabilitation, a delayed penetrating keratoplasty is required.

Examining the Agreement of Structural Loss Measured With Heidelberg Retinal Tomograhy and Functional Loss With Standard Automated Perimetry (SAP; Octopus), Pulsar Perimetry (PP), and Moorfields Motion Displacement Test (MDT) Perimetry

Purpose: To examine the relationship of functional measurements with structural measures. Methods: 146 eyes of 83 test subjects underwent Heidelberg Retinal Tomography (HRTIII) (disc area<2.43, mphsd<40), and perimetry testing with Octopus (SAP; Dynamic), Pulsar (PP; TOP) and Moorfields MDT (ESTA). Glaucoma was defined as progressive structural or functional loss (20 eyes). Perimetry test points were grouped into 6 sectors based on the estimated optic nerve head angle into which the associated nerve fiber bundle enters (Garway-Heath map). Perimetry summary measures (PSM) (MD SAP/ MD PP/ PTD MDT) were calculated from the average total deviation of each measured threshold from the normal for each sector. We calculated the 95% significance level of the sectorial PSM from the respective normative data. We calculated the percentage agreement with group1 (G1), healthy on HRT and within normal perimetric limits, and group 2 (G2), abnormal on HRT and outside normal perimetric limits. We also examined the relationship of PSM and rim area (RA) in those sectors classified as abnormal by MRA (Moorfields Regression Analysis) of HRT. Results: The mean age was 65 (range= [37, 89]). The global sensitivity versus specificity of each instrument in detecting glaucomatous eyes was: MDT 80% vs. 88%, SAP 80% vs. 80%, PP 70% vs. 89% and HRT 80% vs. 79%. Highest percentage agreement of HRT (respectively G1, G2, sector) with PSM were MDT (89%, 57%, nasal superior), SAP (83%, 74%, temporal superior), PP (74%, 63%, nasal superior). Globally percentage agreement (respectively G1, G2) was MDT (92%, 28%), SAP (87%, 40%) and PP (77%, 49%). Linear regression showed there was no significant trend globally associating RA and PSM. However, sectorally the supero-nasal sector had a statistically significant (p<0.001) trend with each instrument, the associated r2 coefficients are (MDT 0.38 SAP 0.56 and PP 0.39). Conclusions: There were no significant differences in global sensitivity or specificity between instruments. Structure-function relationships varied significantly between instruments and were consistently strongest supero-nasally. Further studies are required to investigate these relationships in detail.