Biomarkers and Surrogate Endpoints in Drug Development: A European Regulatory View.


Purpose:To give a European regulatory overview of the requirements on and the use of biomarkers or surrogate endpoints in the development of drugs for ocular disease. Methods:Definitions, methods to validate new markers, and circumstances where surrogate endpoints can be appropriate are summarized. Results:The key endpoints that have been used in registration studies so far are based on visual acuity, signs, and symptoms, or on surrogate endpoints. In some ocular conditions, established outcome measures such as those based on visual acuity or visual field are not feasible (as with slowly progressing diseases), or lack relevance (e.g., when central visual acuity may be preserved even though the patient is legally blind owing to a severely restricted visual field, or vice versa). Conclusions:There are several ocular conditions for which there is an unmet medical need. In some of these conditions, surrogate endpoints as well as new clinical endpoints are needed to help speed up patient access to new medicines. Interaction with European regulators through the pathway specific for the development of biomarkers or novel methods is encouraged.


Wickström K,Moseley J




Has Abstract


2017-05-01 00:00:00














  • Postural stability and gait among older adults with age-related maculopathy.

    abstract:PURPOSE:To assess the postural stability and gait characteristics of adults with age-related maculopathy (ARM) and to identify the visual factors associated with postural stability and gait in this clinical population. METHODS:Participants included 80 individuals with a range of severity of ARM (mean age, 77.2 years)....

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Wood JM,Lacherez PF,Black AA,Cole MH,Boon MY,Kerr GK

    更新日期:2009-01-01 00:00:00

  • Quality of life in patients with leber hereditary optic neuropathy.

    abstract:PURPOSE:Leber hereditary optic neuropathy (LHON) is an inherited mitochondrial optic neuropathy characterized by bilateral, severe loss of central vision. In this study, the first formal assessment was conducted of visual disability in affected and unaffected individuals from molecularly confirmed LHON pedigrees. METH...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Kirkman MA,Korsten A,Leonhardt M,Dimitriadis K,De Coo IF,Klopstock T,Griffiths PG,Hudson G,Chinnery PF,Yu-Wai-Man P

    更新日期:2009-07-01 00:00:00

  • Asymmetry of focal ERG in human macular region.

    abstract::Electroretinograms (ERGs) were elicited by hemicircular (half-disc) stimuli to the upper, lower, temporal and nasal maculas of 26 normal subjects, and the amplitudes and implicit times of the ERGs from opposing macular regions were compared. The amplitudes of a-wave, b-wave and oscillatory potentials (OPs) were signif...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Miyake Y,Shiroyama N,Horiguchi M,Ota I

    更新日期:1989-08-01 00:00:00

  • Factors influencing self-reported vision-related activity limitation in the visually impaired.

    abstract:PURPOSE:The use of patient-reported outcome (PRO) measures to assess self-reported difficulty in visual activities is common in patients with impaired vision. This study determines the visual and psychosocial factors influencing patients' responses to self-report measures, to aid in understanding what is being measured...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Tabrett DR,Latham K

    更新日期:2011-07-15 00:00:00

  • Conventional pattern-reversal VEPs are not equivalent to summed multifocal VEPs.

    abstract:PURPOSE:To compare conventional pattern-reversal visual evoked potentials (cVEPs) with multifocal VEPs (mfVEPs). METHODS:mfVEPs and cVEPs were recorded during the same session in 12 normal subjects with an active electrode at Oz referenced to the inion (Oz-In) or to a midfrontal position, Fz (Oz-Fz). The mfVEP stimulu...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Fortune B,Hood DC

    更新日期:2003-03-01 00:00:00

  • In Vivo Three-Dimensional Lamina Cribrosa Strains in Healthy, Ocular Hypertensive, and Glaucoma Eyes Following Acute Intraocular Pressure Elevation.

    abstract:Purpose:To compare in vivo lamina cribrosa (LC) strains (deformations) following acute IOP elevation in healthy, glaucoma, and ocular hypertensive subjects. Methods:There were 20 healthy, 20 high-tension primary open-angle glaucoma (POAG), 16 primary angle-closure glaucoma (PACG), and 20 ocular hypertensive (OHT; with...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Beotra MR,Wang X,Tun TA,Zhang L,Baskaran M,Aung T,Strouthidis NG,Girard MJA

    更新日期:2018-01-01 00:00:00

  • Synergistic effect of platelet-activating factor and tumor necrosis factor-alpha on corneal myofibroblast apoptosis.

    abstract:PURPOSE:Elimination of myofibroblasts after repair of corneal injury is essential for the maintenance of corneal transparency. In the current study, the role of platelet-activating factor (PAF) in combination with tumor necrosis factor (TNF)-alpha in corneal myofibroblast apoptosis was explored. METHODS:Porcine cornea...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: He J,Bazan HE

    更新日期:2006-03-01 00:00:00

  • Localization of corneal epithelial stem cells in the developing rat.

    abstract::A monoclonal antibody, 4G10.3, was developed that preferentially binds limbal basal cells in adult rat, rabbit, and human corneas. These cells were hypothesized to be the stem cells for the corneal epithelium. The antibody 4G10.3 was localized by immunofluorescence microscopy in rats 1 d and 1, 1.5, 2, 3, 4, and 6 wk ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Chung EH,Bukusoglu G,Zieske JD

    更新日期:1992-06-01 00:00:00

  • The effects of iodate and iodoacetate on the retinal adhesion.

    abstract::Sodium iodate and sodium iodoacetate were employed as biological probes to evaluate component forces contributing to the strength of retinal adhesion to the retinal pigment epithelium (RPE). Iodate treatment produced a rapid reduction in the strength of adhesion, which was complete within 1 hr without evidence of conc...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Ashburn FS Jr,Pilkerton AR,Rao NA,Marak GE

    更新日期:1980-12-01 00:00:00

  • Blue flash ERG PhNR changes associated with poor long-term glycemic control in adolescents with type 1 diabetes.

    abstract:PURPOSE:To investigate the relationship between long-term glycemic control and photopic negative response (PhNR) changes in the blue flash ERG in adolescents with type 1 diabetes (T1D) without diabetic retinopathy (DR). METHODS:After light adaptation, ERG responses to 1.60 cd·s/m(2) blue (420 nm) flashes (blue flash E...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: McFarlane M,Wright T,Stephens D,Nilsson J,Westall CA

    更新日期:2012-02-13 00:00:00

  • Impaired Spatial Hearing in Amblyopia: Evidence for Calibration of Auditory Maps by Retinocollicular Input in Humans.

    abstract:Purpose:Evidence from animals and blind humans suggests that early visual experience influences the developmental calibration of auditory localization. Hypothesizing that unilateral amblyopia may involve cross-modal deficits in spatial hearing, we measured the precision and accuracy of sound localization in humans with...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Richards MD,Goltz HC,Wong AMF

    更新日期:2019-03-01 00:00:00

  • Amyloid β1-43 Accumulates in the Lens Epithelium of Cortical Opacification in Japanese Patients.

    abstract:Purpose:We investigated the accumulation of amyloid β (Aβ1-40, Aβ1-42, Aβ1-43) in the lens epithelium of patients with opacification of five different types (cortical cataract [COR]; nuclear cataract [NUC]; posterior subcapsular cataract [PSC]; retrodots [RD]; and water clefts [WC]). Methods:Samples were collected fro...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Nagai N,Mano Y,Otake H,Shibata T,Kubo E,Sasaki H

    更新日期:2017-06-01 00:00:00

  • Repeatability of manual subfoveal choroidal thickness measurements in healthy subjects using the technique of enhanced depth imaging optical coherence tomography.

    abstract:PURPOSE:The aim of this study was to investigate the repeatability of manual measurements of choroidal thickness in healthy subjects imaged on spectral domain optical coherence tomography (OCT) using the enhanced depth imaging (EDI) technique. METHODS:Fifty consecutive, healthy, young, adult volunteers with no known e...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Rahman W,Chen FK,Yeoh J,Patel P,Tufail A,Da Cruz L

    更新日期:2011-04-08 00:00:00

  • Subconjunctival injections. Preservative-related changes in the corneal endothelium.

    abstract::The morphologic effects on rabbit corneal endothelium of several common ophthalmic vehicle constituents were examined following subconjunctival administration. Profound dose-dependent changes consisting of intercellular vacuolization and thickening of the endothelial layer were noted within 1 day following administrat...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Weinreb RN,Wood I,Tomazzoli L,Alvarado J

    更新日期:1986-04-01 00:00:00

  • Opsin- and S-antigen-like immunoreactions in photoreceptors of the tree shrew retina.

    abstract::In the tree shrew retina individual rod and cone photoreceptors can be readily identified and quantified because their perikarya are arranged in a single layer. This retina is therefore an ideal system for testing the specificity of photoreceptor-directed antibodies. Here we describe the staining properties of polyclo...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Müller B,Peichl L,De Grip WJ,Gery I,Korf HW

    更新日期:1989-03-01 00:00:00

  • Identification of the retinal pigment epithelium protein RET-PE2 as CE-9/OX-47, a member of the immunoglobulin superfamily.

    abstract:PURPOSE:To identify the retinal pigment epithelium (RPE) surface antigen recognized by the monoclonal antibody RET-PE2. METHODS:A lambda bacteriophage complementary DNA (cDNA) expression library, representing the rat RPE cell line RPE-J, was constructed and screened with the RET-PE2 monoclonal antibody. Transient tran...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Finnemann SC,Marmorstein AD,Neill JM,Rodriguez-Boulan E

    更新日期:1997-10-01 00:00:00

  • Cell-mediated immune tolerance to HSV-1 antigens associated with reduced susceptibility to HSV-1 corneal lesions.

    abstract::We have investigated the involvement of cell-mediated immune responses to Herpes simplex virus type 1 (HSV-1) in the pathogenesis of HSV-1 induced corneal stromal lesions in mice. Topical corneal (TC) HSV-1 infection induced a vigorous delayed hypersensitivity response, as well as lymphoproliferative and cytotoxic res...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Ksander BR,Hendricks RL

    更新日期:1987-12-01 00:00:00

  • Diagnostic Power of Lamina Cribrosa Depth and Curvature in Glaucoma.

    abstract:Purpose:To compare the capability of the lamina cribrosa depth (LCD) and lamina cribrosa (LC) curvature in discriminating between eyes with primary open-angle glaucoma (POAG) and healthy eyes. Methods:Seventy-seven eyes of 77 patients with POAG and 77 eyes of 77 healthy subjects who were matched for age, sex, and axia...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Lee SH,Kim TW,Lee EJ,Girard MJ,Mari JM

    更新日期:2017-02-01 00:00:00

  • Modulation of Tmem135 Leads to Retinal Pigmented Epithelium Pathologies in Mice.

    abstract:Purpose:Aging is a critical risk factor for the development of retinal diseases, but how aging perturbs ocular homeostasis and contributes to disease is unknown. We identified transmembrane protein 135 (Tmem135) as a gene important for regulating retinal aging and mitochondrial dynamics in mice. Overexpression of Tmem1...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Landowski M,Grindel S,Shahi PK,Johnson A,Western D,Race A,Shi F,Benson J,Gao M,Santoirre E,Lee WH,Ikeda S,Pattnaik BR,Ikeda A

    更新日期:2020-10-01 00:00:00

  • Recurrent HSV-1 corneal lesions in rabbits induced by cyclophosphamide and dexamethasone.

    abstract::Herpes simplex virus type 1 (HSV-1) ocular shedding and recurrent corneal epithelial lesions were assessed following an intravenous injection of cyclophosphamide (75 mg/kg) and 24 hr later an intravenous injection of dexamethasone (4 mg/kg) in 24 eyes of 15 rabbits latently infected with HSV-1 strain McKrae. Sampling ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Haruta Y,Rootman DS,Xie LX,Kiritoshi A,Hill JM

    更新日期:1989-03-01 00:00:00

  • Inhibition of RAP1 enhances corneal recovery following alkali injury.

    abstract:PURPOSE:Recently, RAP1 (Telomeric Repeat Binding Factor 2, Interacting Protein [TERF2IP]) was discovered as a modulator that selectively regulates nuclear factor light chain kappa enhancer of activated B cells (NFκB) signaling. The roles of RAP1 in regulation of inflammation and angiogenesis for corneal recovery follow...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Poon MW,Yan L,Jiang D,Qin P,Tse HF,Wong IY,Wong DS,Tergaonkar V,Lian Q

    更新日期:2015-01-08 00:00:00

  • Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290.

    abstract:Purpose:To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients. Methods:Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Fov...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Valkenburg D,van Cauwenbergh C,Lorenz B,van Genderen MM,Bertelsen M,Pott JR,Coppieters F,de Zaeytijd J,Thiadens AAHJ,Klaver CCW,Kroes HY,van Schooneveld MJ,Preising M,Hoyng CB,Leroy BP,van den Born LI,Collin RWJ

    更新日期:2018-09-04 00:00:00

  • IMI - Clinical Myopia Control Trials and Instrumentation Report.

    abstract::The evidence-basis based on existing myopia control trials along with the supporting academic literature were reviewed; this informed recommendations on the outcomes suggested from clinical trials aimed at slowing myopia progression to show the effectiveness of treatments and the impact on patients. These outcomes wer...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章,评审


    authors: Wolffsohn JS,Kollbaum PS,Berntsen DA,Atchison DA,Benavente A,Bradley A,Buckhurst H,Collins M,Fujikado T,Hiraoka T,Hirota M,Jones D,Logan NS,Lundström L,Torii H,Read SA,Naidoo K

    更新日期:2019-02-28 00:00:00

  • Syndromic choroideremia: sublocalization of phenotypes associated with Martin-Probst deafness mental retardation syndrome.

    abstract:PURPOSE:To identify the mutation leading to syndromic choroideremia (CHM) in two families and to define fundus autofluorescence (FAF) in CHM carriers. METHODS:The ophthalmic and clinical phenotype was investigated including FAF, neuropediatric, otorhinolaryngologic, cardiologic, and nephrologic examinations of three m...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Poloschek CM,Kloeckener-Gruissem B,Hansen LL,Bach M,Berger W

    更新日期:2008-09-01 00:00:00

  • The prevalence and incidence of epiretinal membranes in eyes with inactive extramacular CMV retinitis.

    abstract:PURPOSE:To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). METHODS:A case-control report from a longitudinal multicenter observational study by the Studies of the Ocular ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章,多中心研究


    authors: Kozak I,Vaidya V,Van Natta ML,Pak JW,May KP,Thorne JE,Studies of the Ocular Complications of AIDS Research Group.

    更新日期:2014-06-12 00:00:00

  • Melatonin receptors in chick ocular tissues: implications for a role of melatonin in ocular growth regulation.

    abstract:PURPOSE:The influences of diurnal rhythms involving a variety of ocular parameters are implicated in the development of myopia. The purpose of this study was to determine the expression of the melatonin receptor subtype proteins in chick ocular tissues and to examine the role of the circadian signaling molecule melaton...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Rada JA,Wiechmann AF

    更新日期:2006-01-01 00:00:00

  • Multiplex bead analysis of vitreous humor of patients with vitreoretinal disorders.

    abstract:PURPOSE:Vitreoretinal disorders are frequently characterized by increased vitreous levels of cellular mediators, including cytokines, chemokines, and growth factors. The study was conducted to investigate whether multiplex bead analysis could identify disease-specific profiles of these mediators in a variety of vitreor...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Banerjee S,Savant V,Scott RA,Curnow SJ,Wallace GR,Murray PI

    更新日期:2007-05-01 00:00:00

  • Endogenic regulation of proliferation and zinc transporters by pigment epithelial cells nonvirally transfected with PEDF.

    abstract:PURPOSE:Genetic modification of cells before transplantation may allow the delivery of neuroprotective and other functional molecules to patients with neurodegenerative diseases. To avoid complications associated with virally transfected cells, we have explored the use of nonviral methods to insert genetic material int...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Johnen S,Kazanskaya O,Armogan N,Stickelmann C,Stöcker M,Walter P,Thumann G

    更新日期:2011-07-23 00:00:00

  • Stimulation of P2X7 receptors elevates Ca2+ and kills retinal ganglion cells.

    abstract:PURPOSE:Retinal ganglion cells are known to express ionotropic P2X(7) receptors for ATP. Stimulation of these receptors in other cells can elevate Ca(2+) and sometimes lead to cell death. This study asked whether P2X(7) receptor stimulation alters the Ca(2+) levels and viability of retinal ganglion cells. METHODS:P2X(...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Zhang X,Zhang M,Laties AM,Mitchell CH

    更新日期:2005-06-01 00:00:00

  • Hydrogen peroxide accumulation in the choroid during intermittent hypoxia increases risk of severe oxygen-induced retinopathy in neonatal rats.

    abstract:PURPOSE:Extremely low gestational age neonates (ELGANs) requiring oxygen therapy often experience frequent episodes of intermittent hypoxia (IH) and are at high risk for severe retinopathy of prematurity (ROP). Using an established model for oxygen-induced retinopathy (OIR), we examined the hypothesis that there is a c...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Beharry KD,Cai CL,Sharma P,Bronshtein V,Valencia GB,Lazzaro DR,Aranda JV

    更新日期:2013-11-19 00:00:00