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Article ; Online: Morning Glory Disc Anomaly in an Infant.

Landsend, Erlend C S / Svenøy, Lise Ellefsen / Ladstein, Gunn Elin

Journal of pediatric ophthalmology and strabismus

2022 Volume 60, Issue 1, Page(s) 75

MeSH term(s)	Humans ; Infant ; Optic Nerve/abnormalities ; Optic Disk/diagnostic imaging
Language	English
Publishing date	2022-06-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	800921-1
ISSN	1938-2405 ; 0191-3913
ISSN (online)	1938-2405
ISSN	0191-3913
DOI	10.3928/01913913-20220526-02
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Article ; Online: Authors' response to letter to the editor: Congenital aniridia - a comprehensive review of clinical features and therapeutic approach.

Landsend, Erlend C S / Lagali, Neil / Utheim, Tor P

Survey of ophthalmology

2021 Volume 67, Issue 2, Page(s) 629–630

MeSH term(s)	Aniridia/therapy ; Humans
Language	English
Publishing date	2021-11-05
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	391346-6
ISSN	1879-3304 ; 0039-6257
ISSN (online)	1879-3304
ISSN	0039-6257
DOI	10.1016/j.survophthal.2021.11.001
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Article ; Online: Congenital aniridia - A comprehensive review of clinical features and therapeutic approaches.

Landsend, Erlend C S / Lagali, Neil / Utheim, Tor P

Survey of ophthalmology

2021 Volume 66, Issue 6, Page(s) 1031–1050

Abstract: Congenital aniridia is a rare genetic eye disorder with total or partial absence of the iris from birth. In most cases the genetic origin of aniridia is a mutation in the PAX6 gene, leading to involvement of most eye structures. Hypoplasia of the fovea ... ...

Abstract	Congenital aniridia is a rare genetic eye disorder with total or partial absence of the iris from birth. In most cases the genetic origin of aniridia is a mutation in the PAX6 gene, leading to involvement of most eye structures. Hypoplasia of the fovea is usually present and is associated with reduced visual acuity and nystagmus. Aniridia-associated keratopathy, glaucoma, and cataract are serious and progressive complications that can further reduce visual function. Treatment of the ocular complications of aniridia is challenging and has a high risk of side effects. New approaches such as stem cell therapy may, however, offer better prognoses. We describe the various ocular manifestations of aniridia, with a special focus on conditions that commonly require treatment. We also review the growing literature reporting systemic manifestations of the disease.
MeSH term(s)	Aniridia/genetics ; Aniridia/therapy ; Cataract/complications ; Corneal Diseases ; Glaucoma/complications ; Humans ; Iris
Language	English
Publishing date	2021-03-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391346-6
ISSN	1879-3304 ; 0039-6257
ISSN (online)	1879-3304
ISSN	0039-6257
DOI	10.1016/j.survophthal.2021.02.011
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Article: Change in Ocular Surface Staining during Eyelid Warming Is Related to Tear Cytokine Levels.

Landsend, Erlend C S / Olafsson, Jonatan / Lai, Xiaoran / Aass, Hans C D / Utheim, Tor P

Journal of ophthalmology

2022 Volume 2022, Page(s) 5103231

Abstract: Purpose: To investigate the changes in the tear cytokine profile of patients with meibomian gland dysfunction (MGD) treated with eyelid warming and to correlate these changes with clinical parameters for dry eye disease (DED).: Methods: Seventy ... ...

Abstract	Purpose: To investigate the changes in the tear cytokine profile of patients with meibomian gland dysfunction (MGD) treated with eyelid warming and to correlate these changes with clinical parameters for dry eye disease (DED). Methods: Seventy patients with MGD were included and treated with the warming of eyelids. Of these, 61 still used the treatment three months after baseline, while 48 completed the whole treatment period of six months. The concentrations of 39 cytokines in the tear fluid were measured at baseline and after three and six months of treatment. All participants were examined with tests for DED, including tear film break-up time (TBUT), ocular surface staining (OSS), and the self-reporting Ocular Surface Disease Index (OSDI). Changes in cytokine concentrations were assessed from baseline to three months, from three to six months, and from baseline to six months. Correlation analyses were performed between changes in the cytokine concentrations and changes in TBUT, OSS, and OSDI during the same time intervals. Results: No significant changes were found in the concentrations of the 39 cytokines during any of the three treatment intervals. However, several correlations were detected between changes in the level of cytokines and OSS from baseline to three months of treatment. Decreasing concentrations of granulocyte chemotactic protein 2 (GCP-2/CXCL6, mean effect 2.36, Conclusions: Warming of eyelids did not change the concentration of cytokines in the tear fluid of patients with MGD significantly. However, alterations in the level of several cytokines were associated with changes in the OSS. This finding indicates a close connection between tear cytokines and OSS in MGD patients treated with eyelid warming.
Language	English
Publishing date	2022-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2546525-9
ISSN	2090-0058 ; 2090-004X
ISSN (online)	2090-0058
ISSN	2090-004X
DOI	10.1155/2022/5103231
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Article ; Online: Rod and Cone Dark Adaptation in Congenital Aniridia and Its Association With Retinal Structure.

Pedersen, Hilde R / Gilson, Stuart J / Landsend, Erlend C S / Utheim, Øygunn A / Utheim, Tor P / Baraas, Rigmor C

Investigative ophthalmology & visual science

2023 Volume 64, Issue 4, Page(s) 18

Abstract: Purpose: To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia.: Methods: Dark-adaptation curves were measured after a 5-minute exposure to bright light with red (625 nm) and ... ...

Abstract	Purpose: To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia. Methods: Dark-adaptation curves were measured after a 5-minute exposure to bright light with red (625 nm) and green (527 nm) 2° circular light stimuli presented at ≈20° temporal retinal eccentricity in 27 participants with aniridia (nine males; 11-66 years old) and 38 age-matched healthy controls. A two-stage exponential model was fitted to each participant's responses to determine their cone and rod thresholds over time. The thicknesses of macular inner and outer retinal layers were obtained from optical coherence tomography images in 20 patients with aniridia and the 38 healthy controls. Aniridia-associated keratopathy (AAK) grade (0-3) and lens opacities were quantified by clinical examination of the anterior segment. Results: The rod-cone break time was similar between patients with aniridia and healthy controls. Dark-adapted cone and the rod thresholds were higher in aniridia compared with healthy controls. In aniridia, foveal outer retinal layer thickness correlated with both final cone and rod thresholds. A multiple regression model indicated that foveal outer retinal layer thickness and age were the main explanatory variables to predict both final cone and rod thresholds in aniridia when the AAK grade was 2 or less. Conclusions: The results show that both rod- and cone-related functions are affected in PAX6-related aniridia and suggest that retinal anatomical and physiological changes extend beyond the area commonly studied in this condition: the central macula.
MeSH term(s)	Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Dark Adaptation ; Retina ; Retinal Cone Photoreceptor Cells ; Photoreceptor Cells, Vertebrate/physiology ; Vision Disorders ; Corneal Diseases ; Aniridia/diagnosis ; Tomography, Optical Coherence/methods
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.64.4.18
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Article ; Online: PAX6 Genotypic and Retinal Phenotypic Characterization in Congenital Aniridia.

Pedersen, Hilde R / Baraas, Rigmor C / Landsend, Erlend C S / Utheim, Øygunn A / Utheim, Tor P / Gilson, Stuart J / Neitz, Maureen

Investigative ophthalmology & visual science

2020 Volume 61, Issue 5, Page(s) 14

Abstract: Purpose: To investigate the association between PAX6 genotype and macular morphology in congenital aniridia.: Methods: The study included 37 participants (15 males) with congenital aniridia (aged 10-72 years) and 58 age-matched normal controls (18 ... ...

Abstract	Purpose: To investigate the association between PAX6 genotype and macular morphology in congenital aniridia. Methods: The study included 37 participants (15 males) with congenital aniridia (aged 10-72 years) and 58 age-matched normal controls (18 males). DNA was isolated from saliva samples. PAX6 exons, intron/exon junctions, and known regulatory regions were amplified in PCR and sequenced. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect larger deletions or duplications in PAX6 or known cis-regulatory regions. Spectral-domain optical coherence tomography images were acquired and segmented semiautomatically. Mean thicknesses were calculated for inner and outer retinal layers within the macula along nasal and temporal meridians. Results: Mutations in PAX6 or regulatory regions were found in 97% of the participants with aniridia. Foveal hypoplasia was observed in all who had a mutation within the PAX6 gene. Aniridic eyes had thinner outer retinal layers than controls, but with large between-individual variation (mean ± SD, 156.3 ± 32.3 µm vs 210.8 ± 12.3 µm, P < 0.001). Parafoveal and perifoveal inner and outer retinal layers were thinner in aniridia. Participants with mutations in noncoding PAX6 regions had thicker foveal outer retinal layers than those with mutations in the PAX6 coding regions (P = 0.04) and showed signs of postnatal development and maturation. Mutations outside the PAX6 gene were associated with the mildest retinal phenotypes. Conclusions: PAX6 mutations are associated with significant thinning of macular inner and outer retinal layers, consistent with misdirected retinal development resulting in abnormal foveal formation and reduced number of neurons in the macula, with mutations in PAX6 coding regions giving the worst outcome.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aniridia/genetics ; Case-Control Studies ; Child ; Female ; Fovea Centralis/abnormalities ; Fovea Centralis/diagnostic imaging ; Genotype ; Humans ; Male ; Middle Aged ; Mutation ; Open Reading Frames/genetics ; PAX6 Transcription Factor/genetics ; Phenotype ; Retina/abnormalities ; Retina/diagnostic imaging ; Tomography, Optical Coherence ; Young Adult
Chemical Substances	PAX6 Transcription Factor
Language	English
Publishing date	2020-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.61.5.14
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Article ; Online: The Cone Photoreceptor Mosaic in Aniridia: Within-Family Phenotype-Genotype Discordance.

Pedersen, Hilde R / Neitz, Maureen / Gilson, Stuart J / Landsend, Erlend C S / Utheim, Øygunn Aas / Utheim, Tor Paaske / Baraas, Rigmor C

Ophthalmology. Retina

2019 Volume 3, Issue 6, Page(s) 523–534

Abstract: Purpose: Investigate in vivo cone photoreceptor structure in familial aniridia caused by deletion in the PAX6 gene to elucidate the complexity of between-individual variation in retinal phenotype.: Design: Descriptive case-control study.: ... ...

Abstract	Purpose: Investigate in vivo cone photoreceptor structure in familial aniridia caused by deletion in the PAX6 gene to elucidate the complexity of between-individual variation in retinal phenotype. Design: Descriptive case-control study. Participants: Eight persons with congenital aniridia (40-66 yrs) from 1 family and 33 normal control participants (14-69 yrs), including 7 unaffected family members (14-53 yrs). Methods: DNA was isolated from saliva samples and used in polymerase chain reaction analysis to amplify and sequence exons and intron or exon junctions of the PAX6 gene. High-resolution retinal images were acquired with OCT and adaptive optics scanning light ophthalmoscopy. Cone density (CD; in cones per square millimeter) and mosaic regularity were estimated along nasal-temporal meridians within the central 0° to 5° eccentricity. Horizontal spectral-domain OCT line scans were segmented to analyze the severity of foveal hypoplasia (FH) and to measure retinal layer thicknesses. Main outcomes and measures: Within-family variability in macular retinal layer thicknesses, cone photoreceptor density, and mosaic regularity in aniridia compared with normal control participants. Results: DNA sequencing revealed a known PAX6 mutation (IV2-2delA). Those with aniridia showed variable iris phenotype ranging from almost normal appearance to no iris. Four participants with aniridia demonstrated FH grade 2, 2 demonstrated grade 3 FH, and 1 demonstrated grade 4 FH. Visual acuity ranged from 0.20 to 0.86 logarithm of the minimum angle of resolution. Adaptive optics scanning light ophthalmoscopy images were acquired from 5 family members with aniridia. Foveal CD varied between 19 899 and 55 128 cones/mm Conclusions: The results showed considerable variability in foveal development within a family carrying the same PAX6 mutation. This, together with the structural and functional variability within each grade of foveal hypoplasia, underlines the importance of advancing knowledge about retinal cellular phenotype in aniridia.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aniridia/diagnosis ; Aniridia/genetics ; Aniridia/metabolism ; Case-Control Studies ; Cell Count ; DNA/genetics ; DNA Mutational Analysis ; Female ; Gene Deletion ; Genotype ; Humans ; Male ; Middle Aged ; Ophthalmoscopy ; PAX6 Transcription Factor/genetics ; PAX6 Transcription Factor/metabolism ; Phenotype ; Retinal Cone Photoreceptor Cells/metabolism ; Retinal Cone Photoreceptor Cells/pathology ; Tomography, Optical Coherence/methods ; Visual Acuity ; Young Adult
Chemical Substances	PAX6 Transcription Factor ; PAX6 protein, human ; DNA (9007-49-2)
Language	English
Publishing date	2019-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2468-7219
ISSN (online)	2468-7219
DOI	10.1016/j.oret.2019.01.020
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Article ; Online: Color Vision in Aniridia.

Pedersen, Hilde R / Hagen, Lene A / Landsend, Erlend C S / Gilson, Stuart J / Utheim, Øygunn A / Utheim, Tor P / Neitz, Maureen / Baraas, Rigmor C

Investigative ophthalmology & visual science

2018 Volume 59, Issue 5, Page(s) 2142–2152

Abstract: Purpose: To assess color vision and its association with retinal structure in persons with congenital aniridia.: Methods: We included 36 persons with congenital aniridia (10-66 years), and 52 healthy, normal trichromatic controls (10-74 years) in the ...

Abstract	Purpose: To assess color vision and its association with retinal structure in persons with congenital aniridia. Methods: We included 36 persons with congenital aniridia (10-66 years), and 52 healthy, normal trichromatic controls (10-74 years) in the study. Color vision was assessed with Hardy-Rand-Rittler (HRR) pseudo-isochromatic plates (4th ed., 2002); Cambridge Color Test and a low-vision version of the Color Assessment and Diagnosis test (CAD-LV). Cone-opsin genes were analyzed to confirm normal versus congenital color vision deficiencies. Visual acuity and ocular media opacities were assessed. The central 30° of both eyes were imaged with the Heidelberg Spectralis OCT2 to grade the severity of foveal hypoplasia (FH, normal to complete: 0-4). Results: Five participants with aniridia had cone opsin genes conferring deutan color vision deficiency and were excluded from further analysis. Of the 31 with aniridia and normal opsin genes, 11 made two or more red-green (RG) errors on HRR, four of whom also made yellow-blue (YB) errors; one made YB errors only. A total of 19 participants had higher CAD-LV RG thresholds, of which eight also had higher CAD-LV YB thresholds, than normal controls. In aniridia, the thresholds were higher along the RG than the YB axis, and those with a complete FH had significantly higher RG thresholds than those with mild FH (P = 0.038). Additional increase in YB threshold was associated with secondary ocular pathology. Conclusions: Arrested foveal formation and associated alterations in retinal processing are likely to be the primary reason for impaired red-green color vision in aniridia.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aniridia/physiopathology ; Child ; Color Perception Tests ; Color Vision/physiology ; Color Vision Defects/physiopathology ; Female ; Fovea Centralis/abnormalities ; Humans ; Male ; Middle Aged ; Tomography, Optical Coherence ; Visual Acuity ; Young Adult
Language	English
Publishing date	2018-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.17-23047
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Article ; Online: Characteristics and Utility of Fundus Autofluorescence in Congenital Aniridia Using Scanning Laser Ophthalmoscopy.

Landsend, Erlend C S / Pedersen, Hilde R / Utheim, Øygunn A / Rueegg, Corina S / Baraas, Rigmor C / Lagali, Neil / Bragadóttir, Ragnheidur / Moe, Morten C / Utheim, Tor P

Investigative ophthalmology & visual science

2019 Volume 60, Issue 13, Page(s) 4120–4128

Abstract: Purpose: To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia.: Methods: Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained ... ...

Abstract	Purpose: To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. Methods: Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slit-lamp biomicroscopy. Results: Mean age was 28.4 ± 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 ± 0.15 in aniridia versus 1.18 ± 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). Conclusions: Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia.
MeSH term(s)	Adolescent ; Adult ; Aniridia/diagnostic imaging ; Aniridia/pathology ; Case-Control Studies ; Child ; Female ; Fluorescein Angiography/methods ; Humans ; Male ; Middle Aged ; Ophthalmoscopy/methods ; Prospective Studies ; Tomography, Optical Coherence/methods ; Young Adult
Language	English
Publishing date	2019-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.19-26994
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Article ; Online: The Level of Inflammatory Tear Cytokines is Elevated in Congenital Aniridia and Associated with Meibomian Gland Dysfunction.

Landsend, Erlend C S / Utheim, Øygunn A / Pedersen, Hilde R / Aass, Hans Christian D / Lagali, Neil / Dartt, Darlene A / Baraas, Rigmor C / Utheim, Tor P

Investigative ophthalmology & visual science

2018 Volume 59, Issue 5, Page(s) 2197–2204

Abstract: Purpose: To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings.: Methods: We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I ... ...

Abstract	Purpose: To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. Methods: We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated. Results: The concentrations of six tear cytokines were significantly higher in aniridia patients than controls in both eyes, and included interleukin 1β (IL-1β), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1α (MIP-1α/CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1β was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1β, IL-9, IL-17A, FGF2, and MIP-1α correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film. Conclusions: A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients, and explain the high prevalence of MGD and dry eye disease in these patients.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aniridia/metabolism ; Child ; Cytokines/metabolism ; Eye Proteins/metabolism ; Eyelid Diseases/metabolism ; Eyelid Diseases/pathology ; Female ; Humans ; Male ; Meibomian Glands/metabolism ; Meibomian Glands/pathology ; Middle Aged ; Osmolar Concentration ; Tears/metabolism ; Young Adult
Chemical Substances	Cytokines ; Eye Proteins ; tear proteins
Language	English
Publishing date	2018-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.18-24027
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