Nordic research in ophthalmology

Review Article

Nordic research inophthalmology

Einar Stefansson,1 Charlotta Zetterstrom,2 Niels Ehlers,3

Jens F. Kiilgaard,4 Morten la Cour,4 Haraldur Sigurdsson,1

Elınborg Gudmundsdottir,1 Jan Ulrik Prause4 and Anders Heijl5

1University of Iceland, Reykjavik, Iceland2St Erik’s Eye Hospital, Stockholm, Sweden3University of Aarhus, Denmark4University of Copenhagen, Denmark5Malmo University Hospital, Malmo, Sweden

ABSTRACT.

Purpose: To provide an overview of some of the current activities in eye research

in the Nordic countries.

Methods: The presentations at the biannual Nordic Congress of Ophthalmology,

held in Tampere, Finland in 2002, were reviewed and the contributions found

most noteworthy are included in this article along with a limited discussion of

each research field. However, space requirements prevented the inclusion of many

interesting scientific contributions.

Results: Important contributions in various subfields of eye research and

ophthalmology are reviewed. These include cornea, cataract, paediatric ophthal-

mology, glaucoma, diabetic eye disease, age-related macular degeneration,

physiology and pharmacology and oncology.

Conclusions: Eye research is very active in the Nordic countries and significant

contributions are being made to ophthalmology in several fields on a world scale.

We hope to continue to review Nordic contributions to eye research after each

Nordic Congress of Ophthalmology and plan to make the reviews more system-

atic and comprehensive in the future.

Key words: eye research – cornea – cataract – paediatric ophthalmology – glaucoma – diabetic eye

disease – age-related macular degeneration – ophthalmic oncology

Acta Ophthalmol. Scand. 2003: 81: 556–566Copyright # Acta Ophthalmol Scand 2003.

doi: 10.1046/j.1600-0420.2003.00177.x

Introduction

The Nordic countries have enjoyed along tradition of activity in eye researchand, as demonstrated by the biannualNordic Congress of Ophthalmology,maintain a high level of research activ-ity in ophthalmology today. The 2002Nordic Congress of Ophthalmology,held in Tampere, Finland, provided an

overview of current activities in eyeresearch in the Nordic countries; itnow serves as the basis for this reviewarticle, which attempts to sample andsummarize some of the highlights incurrent Nordic eye research. Theauthors realize that it is impossible todo justice to all eye research in theNordic countries in a short review and

apologize for neglecting some import-ant work.

Recent corneal researchin the Nordic countries

For more than a century, research intocorneal problems has been an import-ant part of Nordic ophthalmology.Recall, for instance, the tonometers ofHjalmar Schiotz, which induced adeformation of the cornea and a disten-sion of the entire eyeball (the concept ofrigidity). A 2002 study approached thesame basic problems by measuring cen-tral corneal thickness, radius of curva-ture and intraocular pressure (IOP) innormal subjects using non-contacttechniques (Eysteinsson et al. 2002).Other important studies to rememberinclude Henrik Forsius’ descriptions ofthe large families in Finland with clin-ically abnormal corneas (e.g. corneaplana and lattice dystrophy). These stud-ies of hereditary dystrophies have beencontinued in Iceland by Jonasson et al.(2002a), who, at the Tampere meeting,reported that many of the genetic defectsare now known in detail. Today, thisinterest in corneal research is still vividlyalive, as can be seen from the abstractsof the XXXV Nordic Congress, held inTampere in August 2002, and from ori-ginal papers published in Acta Ophthal-mologica during 2002. In an attempt to

ACTA OPHTHALMOLOGICA SCANDINAVICA 2003

556

structure this short presentation, thepublished studies have been dividedinto clinical observations and cases, prob-lems related to refractive surgery andpurely experimental studies.

Clinical observations and cases

Stenevi et al. (2002) presented an inter-esting case of survival of donor stemcells after grafting. One eye of a mansuffering from chemical burns wasgrafted with a female donor cornea.After 3 years, 30% of the epithelial cellswere female, as demonstrated by sexchromatin staining. This case is a clin-ical confirmation of the importance thatmust be attached to stem cells and theexpectations of the many experimentalstudies in the field of stem cells per-formed in recent years. Acanthamoebakeratitis is another topic of great interestin Nordic ophthalmology. Floren et al.(2002) discussed three cases seen inSweden in 3months. Two eyes werelost despite heavy treatment.

The confocal microscope is an instru-ment that holds distinct promise forclinical research. It is in routine use inDenmark and Finland. A demonstra-tion of its possibilities in the diagnosisof acanthamoeba keratitis was given inTampere by Møller Pedersen (2002).Meanwhile, Rosenberg et al. (2002)reported the use of confocal micro-scopy to demonstrate the nerves in her-petic keratitis.

Corneal problems related to refractive

surgery

The characterization of the response ofthe corneal stroma to surgery wasreviewed by Fagerholm (2002).Makinenet al. (2002) reported the longterm resultsafterphotorefractivekeratectomy(PRK)for myopia. Aberrations of the opticalsystem represent another hot topic. Theuse of corneal topographic and wholeeye wavefront analysis to customize theexcimer laser ablation has been studiedby Hjortdal (2002).

Experimental studies

In Trondheim, Midelfart et al. (2002 inpress) have applied a very sophisticatedtechnique � high resolution protonmagic angle spinning (MAS) nuclearmagnetic resonance spectroscopy � todescribe the metabolic profile of thecornea. It is possible to identify and

analyse quantitatively a large numberof metabolites in the tissue. So far, stud-ies have been limited to UV radiationand steroid-induced changes.

Trends in cataractsurgery in the Nordiccountries

Cataract surgery in adults is increas-ingly becoming a refractive procedure,which was rather obvious during theXXXV Nordic Congress of Ophthal-mology. In the past, we were happy toget the cataract out and the intraocularlens (IOL) in. Today, we are muchmore concerned about refraction, par-ticularly in terms of astigmatism, andare trying to put the incision in the stepmeridian (Corydon et al. 2002a). Ani-sometropia or disturbances from thefellow eye due to cataract are not unu-sual causes of poor outcome. The high-est degree of improvement in visualfunction was found in subjects under-going cataract surgery of both eyeswithin a short interval. This was foundby outcome studies organized by theSwedish National Cataract Registerand reported by Lundstrom (2002). Itis to be hoped that the idea that one eyeis enough is now history, at least in theNordic countries.

Cataract surgery is becoming muchmore precise in terms of refraction, butit is also much safer. Twelve years ago,complications such as endophthalmitisjeopardized results in around 0.25% ofcases. Montan (2002) reported that thepresent incidence of postoperativeendophthalmitis has declined to 0.04%and that the decisive factor behind thisdecline is the introduction of intra-cameral prophylactic antibiotics. Wejde(2002) analysed risk factors and foundan association between different lensmaterials and postoperative endophthal-mitis. Contrary to common belief, neitherdiabetes, immunosuppression, combinedprocedures with trabeculectomy orcapsular breaks were found to beassociated with increased risk of thisfeared complication.

Many patients and doctors thinkthat visual quality is almost as import-ant as visual acuity (VA) as measuredwith a test chart. This fact has led tointense research, with the aim of find-ing IOLs that give a high degree ofvisual comfort. Corydon et al. (2002b)

found better contrast sensitivity in eyesimplanted with the Pharmacia TecnisZ9000 compared to a conventionalIOL, provided that the pupil was nottoo small. This new IOL compensatesfor the positive spherical aberration ofthe cornea. It is probable that theZ9000 will represent a good option,particularly for younger cataractpatients with larger pupils and activelifestyles that include night-driving.

Another aspect of quality of visionconcerns the necessity for readingglasses. Uusitalo et al. (2002) foundthat a multifocal IOL (AMO Arraymultifocal) gives significantly betternear VA than a monofocal IOL. How-ever, this advantage comes with a price-tag, namely, a reduction in contrastsensitivity, and in some cases glare prob-lems occur. It is to be hoped that wewill, in the future, come up with anIOL that will give equally good qualityof vision, both near and distance, andwill perhaps consist of some injectablematerial which can change its curvatureas our own lenses do in our youth.

Visco-elastic devices are today usedin almost all anterior segment proced-ures. Ohrstrom et al. (2002) foundvisible droplets of silicon oil in someof them. The silicon serves as a lubri-cant for the syringes used for the visco-elastic devices. Silicon oil adheres toIOLs and it is possible that this maycause calcification with hydrophilicpolyhema IOLs. This hypothesis indi-cates the importance of looking at thesurgical procedure as a whole.

Lens extraction in cases with ectopialenses has seen some technical improve-ments in recent years. Koivula &Zetterstrom (2002) reported that today itis possible to retain the capsular bag insuch cases and that the entire surgerycan be performed through a small inci-sion. The technique involves a suturedCionni modified capsular tension ringand an acrylic IOL inserted into theintact and centred lens-capsule. Thistechnique implies that the vitreous isleft untouched and, it is to be hoped,that the retinal detachments that havehitherto occurred not uncommonly inthese cases will be rarer in the future. Inaddition, with a safer technique, chil-dren could be operated on to a largerextent, and amblyopia could beavoided.

In Sweden, screening for congenitalcataract in maternity wards has beenfound to be effective and was discussed


557

by Kugelberg & Magnusson (2002)during the symposium on congenitalcataract.

Implantation of IOLs in childrenover the age of 1 year is a routine pro-cedure in most centres where paediatriccases are looked after. However, after-cataract still remains a problem even ifa posterior capsulorexis is performed.Kugelberg & Zetterstrom (2002) sug-gested that anterior vitrectomy shouldbe performed in children below the ageof 7 years in order to avoid this compli-cation. However, there is still no IOLdesigned to fit the newborn eye. In suchcases, both after-cataract and second-ary glaucoma have to be contendedwith. The latter is very problematicand sometimes sight-threatening. Inthe Nordic countries, contact lensesare a good option, particularly in bilat-eral cases. However, problems withcompliance and amblyopia treatmentare common in unilateral cataract(Lundvall & Kugleberg 2002; Lundvall& Zetterstrom 2002). Intraocular lenseshave been implanted in human newborneyes in subjects with unilateral cataract atSt Erik’s Eye Hospital in Stockholm. Inthese cases, after-cataract and mem-brane formation have been significantproblems (Zetterstrom 2002). It seems,however, that the incidence of secondaryglaucoma is low. Secondary glaucomaafter early surgery may be explained bythe pronounced inflammation seen inthese eyes. Kugelberg et al. (2002)pointed out that topically applied corti-costeroids cause side-effects such as cush-ingoid features and inhibit growth in thenewborn rabbit. This fact must beconsidered when topical corticosteroidsare applied in the human newborn.

In conclusion, the field of cataract isvery dynamic and we can expect to seea lot of improvements in the near futurein the Nordic countries.

Paediatric ophthalmology

At the Tampere meeting, Jacobson et al.(2002a) reported on visual function, eyemotility and optic disc appearance incerebral visual impairment. Braindamage of pre- and perinatal origin,affecting the visual pathways, accountsfor an increasing number of visuallyimpaired children. Lesions to theimmature brain that interrupt axons inthe posterior visual pathways may resultin retro- and antegrade degeneration

and/or reorganization. Differentpatterns of optic disc appearance, eyemotility disturbance and visual dys-function may reflect the stage ofmaturation at which the visual systemwas injured. These children may pre-sent to the ophthalmologist within aclinical spectrum from severe visualimpairment in combination with cere-bral palsy and mental retardation toonly early onset esotropia, normalintellectual level and no cerebral palsy.Jacobson et al. (2002b) have beenworking on visual function and ocularsigns associated with periventricularleukomalacia (PVL) in preterm chil-dren. Periventricular leukomalacia hasbecome a principal cause of visualimpairment in children. Magnetic reson-ance imaging (MRI) is the method ofchoice for diagnosing the lesion.

Considerable effort has been put intothe study of retinopathy of prematurity(ROP). Dinparvar et al. (2002) pre-sented a retrospective study at a postersession at the 2002 Nordic Congress onthe incidence of ROP in one Norwegiancounty (population 435 000), in which itwas found that ROP (any stage)occurred in 32.7% of infants with abirthweight of less than 1500 g. Theincidence of ROP stage 3 was 4.4%.

The current incidence of ROP in theStockholm area in Sweden has beencompared to that in a previous studycarried out 10 years ago in exactly thesame geographical area. The incidenceof ROP was 36.4% in preterm childrenwith a birthweight of 1500 g or less,which was similar to that found in theearlier study (Holmstrom et al. 1993;Larsson et al. 2002). The populationwas different in the second studygroup, with an increased survival rateof extremely immature infants. Themore mature infants ran a lower riskof developing ROP, while the mostimmature infants had an increased riskof ROP. The presenters suggested thatthis is a consequence of modern neo-natology taking better care of the moremature infants and saving the mostimmature and fragile infants, whowould previously not have survived.

Haugen (2001; 2002) studied visualfunction in children with Down’ssyndrome. These children have a signif-icantly elevated prevalence of differentocular and visual disorders. The refrac-tivedevelopmentof childrenwithDown’ssyndrome is different from that ofother children in that the normal

emmetropization process does nottake place. Rather, a wide distributionof refractive value persists, the major-ity of patients being hypermetropic.Accommodation weakness is rathercommon, which may contribute tothe high frequency of refractive errorsencountered in patients with Down’ssyndrome. Bifocals or progressiveglasses should be used in accommoda-tion weakness. Astigmatism is alsovery common and oblique astigma-tism is far more common than is nor-mal. Interestingly, all eyes withoblique astigmatism had a side-speci-fic direction of axis, with the righteyes belonging to the 135 degree axisgroup and the left eyes to the45 degree axis group. This strikingright-left specificity in the obliqueastigmatic eye suggests that mechani-cal factors on the cornea from theupward slanting palpebral fissuresmay be a major aetiological factor inastigmatism. Roughly 30–40% ofDown’s syndrome patients have stra-bismus, mostly acquired esotropiaassociated with hypermetropia and/oraccommodation weakness.

Glaucoma andpseudoexfoliationsyndrome

Thygesen & Kessing (2002) found theincidence of primary congenital glau-coma to be one in 10 000–15 000 births.Diagnosis is based on enlargement ofthe eye, corneal oedema, photophobiaand tearing, whereas the IOP measure-ment under general anaesthesia is lessreliable. Trabeculotomy is the proced-ure of choice and when children areoperated before the age of 6months,the optic nerve cupping is reversed.Jakobsen (2002) also reported goodresults with trabeculotomy for develop-mental glaucoma.

In complicated glaucoma cases, theuse of drainage implant surgery isbecoming more popular. Valimaki(2002) reported on 87 Finnish patientswith refractory glaucoma. The maincomplications were suprachoroidalhaemorrhage in 2%, excessive drainagewith flat anterior chamber in 10% andchoroidal detachment in 13%. Glau-coma drainage tubes have become afrequently used and relatively safe pro-cedure in complicated glaucoma cases(Airaksinen 2002; Vuori 2002).


558

Pseudoexfoliation syndrome was dis-covered in the Nordic countries andthey have maintained a leading role ininvestigating the disorder. It has beenpointed out that the associationbetween pseudoexfoliation syndromeand various systemic vascular diseasesis weak and the evidence contradictory(Hietanen & Kivela 2002; Hietanenet al. 2002). Puska (2002) examinedthe development of unilateral pseudo-exfoliation syndrome to bilateralexfoliation syndrome and glaucoma ina prospective study, and found that38% of patients with unilateral pseudo-exfoliation converted to bilateral pseu-doexfoliation syndrome within10 years and 32�38% developed glau-coma. Mika (2002) found that 45% ofeyes with pseudoexfoliation syndromeand glaucoma showed progression invisual field change within 5 years.

Glaucoma drug treatment

Alm (2002a,b) discussed the develop-ment of latanoprost from prostaglan-din F2a in Sweden. Prostaglandin F2ais a very effective ocular hypotensiveagent and increases uveoscleral out-flow. However, prostaglandin F2a wasfound to be unsuitable for clinical usedue to ocular irritation and conjunc-tival hyperaemia. The analogue latano-prost is also a very potent ocularhypotensive agent and is much less irri-tating. The most common side-effect isincreased pigmentation of the iris anddarker and longer eyelashes. Iritis,uveitis and cystoid macular oedemaare rare complications and it is uncer-tain whether latanoprost is associatedwith reactivation of herpes simplexkeratitis. Larsson (2002) reported on theuse of Xalatan1 in fixed combinationwith timolol, finding this to be moreeffective in reducing IOP than Xalatan1

alone. Thygesen (2002) reported onanother prostaglandin analogue,Travaprost1, which is also a prosta-glandin F2a analogue and a highlyactive ocular hypotensive agent. Itsside-effects include iris pigmentation.

Diagnostics

Bengtsson (2002, 2003) provided anoverview of blue-on-yellow perimetryand the new fast SITA SWAP program.This faster test program is the newestmember of the SITA family of opti-mized, computerized test programs for

computerized perimetry. These pro-grams are now setting new standardsfor computerized perimetry. The sameresearch group has published most ofthe fundamental papers on these tech-nologies in Acta Ophthalmologica(Bengtsson et al. 1997; Bengtsson &Heijl 1998a,b). Dr Bengtsson alsoreported on other new techniques,including a study on visual evokedpotential (VEP) perimetry in glaucomawith rather disappointing results, laterpublished full-length in the journal(Bengtsson 2002).

Grødum et al. (2002a,b) discussedresults from the Malmo Eye Survey,concluding that patients with normaltension glaucoma are often not diag-nosed in the present health care system,and special efforts and increased aware-ness on the part of ophthalmologistsare needed to identify patients withundiagnosed glaucoma, especiallypatients with normal IOP.

Heijl provided an overview of glau-coma research in the Nordic countries,emphasizing that Nordic glaucomaresearch has traditionally been strong.In the past decade, Finnish glaucomaresearch has been especially strong onpseudoexfoliation glaucoma and theretinal nerve fibre layer in glaucoma.Two groups have been particularlyactive in Sweden: the Uppsala group’swork on pharmacological glaucomatreatment has been very important inthe development and study of prosta-glandin analogues, while the Malmogroup has developed important newdiagnostic techniques, particularly inperimetry, and has also been active inepidemiological research and import-ant controlled trials.

Nordic clinical glaucoma researchremains strong. The main problem forNordic glaucoma research is not a lackof strong research groups and funding,but the present lukewarm interest inresearch on the part of Nordic healthcare providers.

Diabetic eye disease

Nordic ophthalmologists have longemphasized the treatment and preven-tion of blindness in diabetic retino-pathy. This has included research intothe epidemiology of diabetic eye diseaseand the efficacy of screening and pre-ventive treatment, technical aspects ofmanaging the disease and research into

its pathophysiology and the mechanismof treatment. At the Nordic Congressin Tampere, Agardh (2002) discussedthe sometimes dramatic scenario of dia-betic retinopathy during pregnancy.Diabetic retinopathy may worsen dur-ing pregnancy with proliferativechanges or diabetic macular oedema.While this frequently improves post-partum, it may cause persistent visualloss. Careful screening of the fundus indiabetic women during pregnancy isrecommended. Sirpa & Risto (2002)studied perifoveal capillary circulationduring pregnancy in women with type 1diabetes and found this to be increased.They suggested that the hyperdynamicretinal circulation may contribute tothe progress of diabetic retinopathyduring pregnancy.

Sjølie (2002) pointed out severalways of altering the development andprogression of retinopathy. Goodmetabolic and blood pressure controlcan diminish the progression of micro-vascular complication in diabetes. Theangiotension converting enzyme inhib-itor lisinopril has been shown to halvethe progression of retinopathy inpatients with normotensive type 1 dia-betes.

Stefansson (2001, 2002) presented atheory on the pathophysiologicalmechanism of retinal photocoagulationand vitrectomy in diabetic eye disease.Retinal laser treatment and vitrectomyboth improve the oxygenation of theinner retina and relieve hypoxia. Thisimproves the retinal haemodynamicsand reduces the production of growthfactors and permeability factors, result-ing in decreased neovascularization andoedema formation. On the same trainof thought, Larsen (2002a) emphasizedthe importance of arterial hypertensionin diabetic macular oedema, stressingthe pathophysiological and therapeuticrole of blood pressure in diabetic eyedisease. The importance of haemo-dynamics is also evident in the venouscongestion that may be seen in diabeticretinopathy, which shows some over-lapping of the characteristics of dia-betic retinopathy and branch retinalvein occlusion (Larsen 2002c).

Bek (2002b) discussed the technicalaspects of screening for diabetic retino-pathy and a system that has been devel-oped to allow digitalized photographicscreening of diabetic retinopathy andthe transfer and analysis of theseimages in a centralized location. Von


559

Wendt et al. (2002) investigated thedetection of retinal neovascularizationin photographic screening. They founda single field 45 degree photograph tobe insufficient and recommended atwo-field 45 degree photographicapproach centred on the macula andoptic disc, despite the fact that thisrevealed only 77% of neovasculariza-tion elsewhere that could be seen oncorresponding two-field 60 degreephotographs. Virtamo et al. (2002)found that diabetic eye disease remainsa significant cause of blindness inFinland, with 4.5% of subjects classi-fied as visually impaired and 2.2% asblind after 25 years’ disease duration.Much remains to be done to preventblindness from diabetes (Stefanssonet al. 2000). Larsen (2002b) presentedan automated system for the detectionof red lesions in the fundus. This has apotential for augmenting the perfor-mance of visual grading and possiblyreplacing visual grading in some patients.Other authors discussed digital imageprocessing to improve resolution andease the detection of lesions on fundusphotographs (Holm 2002; Jensen 2002).

Age-related maculardegeneration

The epidemiology of age-related maculardegeneration (AMD) in Iceland, asfound by the Reykjavik Eye Study, waspresented by Jonasson et al. (2002b). Itappears that the most common pheno-type of late AMD in Iceland is geo-graphic atrophy. This is contrary tofindings in most countries in Europeand North America, where choroidalneovascularization represents the mostcommon form. This variation mayreflect differences in genetic risk factorsor in the environment. Andersen (2002)presented prevalence data on AMD inGreenland, where the prevalence ofgeographic atrophy is also relativelyhigh and the phenotypes differ some-what from those in Iceland. Age-relatedmacular degeneration is the most com-mon cause of blindness in the Nordiccountries, which, accordingly, placegreat emphasis on dealing with this dis-ease. At the Nordic Congress inTampere, Immonen chaired a symposiumon the pathophysiology and treatmentof AMD. Nilson et al. (2002) studiedlipofuscin formation in retinal pigment

epithelial cells in vitro. Lipofuscin pro-duction was found to be increased byhyperoxia and decreased by antioxi-dants such as alpha-tocopherol, lyco-pene and lutein. This may beimportant in the formation of drusen.Frennesson & Nilsson (2002) discussedprophylactic laser treatment of drusen.They are now conducting a large, multi-centre, randomized study in theNordic countries on the outcome of lowintensity argon laser treatment for softdrusen.

The most recent treatment modalitiesfor AMD include photodynamic ther-apy, transpupillary thermotherapy(TTT) and submacular surgery. Algvereet al. (2002) discussed TTT foroccult choroidal neovascularization.This treatment has been the subject ofcontroversy in recent years, but theauthors found their results to comparefavourably with the natural course ofthe disease and results obtained byphotodynamic therapy, and suggestthat TTT should be studied furtherand may have a role to play in thetreatment of AMD. Photodynamictherapy is now better established;Larsen (2002b) discussed clinical experi-ence with photodynamic therapy usingverteporfin for subfoveal choroidal newvessels in AMD. One of the difficultissues is when to retreat. The authorpointed out that persistent subretinalbleeding or lipid precipitation as wellas visible growth of the membrane andfluorescein angiographic leakage areindicators for retreatment. He pro-posed that optical coherence tomo-graphy (OCT) may be a better guidefor retreatment than fluorescein angio-graphy.

Experimental treatmentof degenerative retinaldisorders

Retinal degenerative diseases representmajor causes of visual impairment andblindness in the western world. It isobvious that restoration of some visionmight be possible in these patients if wecould replace defective parts of theretina by transplantation of healthycells and tissues. Over the last threedecades, this idea has been pursued inmore than a thousand articles in thescientific literature. In the Nordic coun-tries, retinal transplantation research

has followed three major avenues.Transplantation of neuroretinal tissuehas been studied extensively for morethan a decade by Berndt Ehinger andhis group in Lund, Sweden, who havemade major contributions to the field.Retinal pigment epithelial transplant-ation and its equivalent iris pigmentepithelial transplantation were pio-neered by Peep Algvere, Stockholm,and by Sven Crafoord and coworkersin Orebro and Stockholm, Sweden.Reconstruction of Bruch’s membraneby transplantation of basement mem-brane material was pioneered byMortenla Cour, Erik Scherfig and Jan UlrikPrause, Copenhagen, Denmark.

The transplantation of neuroretinaltissue is an ambitious project. In orderto establish a functional graft, it isnecessary to obtain neuronal integra-tion of the graft with the host. At leastsome degree of preservation, or restora-tion, of retinal tissue architecture isprobably also necessary. Earlier tech-niques of retinal transplantation involvedaspiration of fetal retinal tissue into asyringe and subsequent injection of thefragmented tissue into the subretinalspace (Aramant et al. 1988, 1990;Ehinger et al. 1991; Juliusson et al. 1993,1994; Bergstrom et al. 1994; Sharma &Ehinger 1997a, 1997b; Sharma et al.1997). Using this early technique, itwas found that embryonic rat and rab-bit neuroretinal tissue transplanted toadult hosts continue to proliferate anddifferentiate (Bergstrom et al. 1994;Zucker et al. 1994; Sharma & Ehinger1997b). The subretinal space is animmunologically privileged site, andgrafts can survive in the host for manymonths, even years, without immuno-suppression (Larsson et al. 1998;Sharma et al. 2000). Furthermore, thetransplanted, fragmented, neuroretinaltissue is capable of light transductionand graft amacrine cells project intothe host retina (Adolph 1994; Zhanget al. 1999). However, in these earlyexperiments the architecture of thetransplanted tissue was abnormal,with rosette formation of the photo-receptors (Juliusson et al. 1993;Bergstrom et al. 1994; Sharma et al.1997).Amajor leap forwardwasobtainedin Lund, Sweden, with the devising of anew surgical technique that enabledtransplantation into the subretinalspace of a full-thickness neuroretinalgraft as a flat sheet of tissue with pre-served orientation (Ghosh et al. 1998,


560

1999a; Ghosh & Arner 2002). With thistechnique, the photoreceptors appearednormal with preserved outer segmentsthat interdigitated with the processes ofthe host retinal pigment epithelium(Ghosh et al. 1998, 1999a; Ghosh &Arner 2002). Integration with the hostwas seen to a higher extent in the full-thickness grafts than in the earlier frag-mented ones, although the hostphotoreceptor layer continued to limitanatomical host–graft interaction(Ghosh et al. 1999a, 1999b, 1999c;Ghosh & Arner 2002; Zhang et al.2003). Whereas fetal, or neonatal,donor tissue was necessary for survivalof fragmented grafts, the use of full-thickness grafts resulted in the survivalof more than 90% of grafts from adultdonors (Wasselius & Ghosh 2001).

Retinal stem cells are pluripotentcells with the capacity to differentiateinto all retinal neuronal cell types.Recently, transplantation of mouse ret-inal stem cells to the subretinal space inpigs has been attempted. Interestingly,the stem cells were found to integratewell into the host retina, but a massiverejection reaction set in within 2weeksof transplantation of these xenografts(Kiilgaard et al. 2003; Warfinge et al.2003). It is to be hoped that thedevelopment of porcine retinal stem cellswill advance this research (Shatos et al.2003).

The gene defects involved in anincreasing number of inherited retinaldegenerations are now known. Genetherapy (i.e. the replacement of defect-ive genes with wild-type genes) is thesubject of intense interest as a potentialcure for these diseases. One of the mostsuccessful examples of gene therapy forretinal dystrophy in an experimentalanimal has been reported for theSwedish Briard dog (Narfstrom et al.2003a, 2003b).Thegenedefect that resultsin retinal dystrophy in this animal residesin the RPE65 gene, which is exclusivelyexpressed in the retinal pigment epithe-lium (RPE), and which is also respon-sible for some cases of Leberscongenital amaurosis in humans(Veske et al. 1999). Key members ofthe group that accomplished this areKristina Narfstrom, formerly ofUppsala, Sweden, now of the Univer-sity of Missouri-Columbia, USA, andRangheidur Bragedottir, of Oslo,Norway.

In experimental animals retinal dys-trophies have been found in which the

primary defect resides in the RPE. Inone such animal, the RCS rat, RPEtransplantation has led to both mor-phological and functional rescue ofphotoreceptors. Transplantation ofRPE is theoretically simpler than neuro-retinal grafting, as the graft is notrequired to form neuronal connectionswith the host. However, no retinaldegeneration in humans is known tobe equivalent to the dystrophy seen inRCS rats. In humans RPE transplant-ation was first tested as a remedy to pre-vent the formation of an atrophic scarafter surgical excision of choroidal neo-vascular tissue in patients with exuda-tive AMD (Algvere et al. 1994, 1997,1999; Crafoord 2002). In these experi-ments, transplantation of freshly isol-ated donor RPE cells or cell sheetsdid not result in visual improvementfor the patients and the presence ofmacular oedema and loss of graft pig-mentation were interpreted as signs ofgraft rejection (Algvere et al. 1994,1997, 1999). Subsequent laboratoryexperiments have shown that RPEcells transplanted to the subretinalspace in rabbits survive for severalmonths without stimulating an immuno-logical reaction (Crafoord et al.1999, 2000b). However, 6months aftertransplantation most of the trans-planted cells were lost, irrespective ofwhether the animals were immunosup-pressed or not (Crafoord et al. 2000a).It is possible that the transplanted RPEcells succumbed to apoptosis inducedby the new environment. Studies inCopenhagen on porcine RPE cells inculture have shown that there is a con-stant loss of these cells to apoptosis.The apparent stability of the culture isa dynamic equilibrium between cellproliferation and apoptosis (Wienckeet al. 2003). Iris pigment epithelial(IPE) cells have been shown to havemany properties similar to RPE cells,and they are much easier to obtainfrom a living individual than RPEcells. The use of autologous IPE cellsfor transplantation reduces the risk ofan immunological reaction to the graft.Recently, autologous IPE cells trans-planted to the subretinal space havebeen shown to survive better than allo-genic RPE cells (Crafoord et al. 2001).Photoreceptor outer segment morph-ology is preserved adjacent to the trans-planted IPE cells (Crafoord 2002).

In AMD, changes in Bruch’s mem-brane are believed to be essential for

the pathogenesis of the disease (laCour et al. 2002). Reconstruction ofBruch’s membrane by transplantationof new basement material has beenattempted in laboratory experimentsin Copenhagen. It has been shownthat transplantation of an anteriorlens capsule to the subretinal space inpigs results in the formation of anintact monolayer of pigmented RPEcells on the surface of the transplantedlens capsule (Nicolini et al. 2000;Kiilgaard et al. 2002b). Similar resultswere found when porcine amniotic mem-brane was used as Bruch’s membranesubstitute (Kiilgaard et al. 2002a).

Physiology andpharmacology

One of the oldest traditions in Nordiceye research concerns the field of ocularphysiology and pharmacology. Overthe last 6 years, researchers at the Uni-versities of Iceland and Copenhagenhave studied the oxygen metabolism ofthe optic nerve in pigs (Jensen et al.2002; Pedersen et al. 2002; Stefanssonet al. 2002). The researchers discoveredthat carbonic anhydrase inhibitors suchas acetazolamide and dorzolamideincrease the oxygen tension of theoptic nerve and retina. The mechanismof this effect is through CO2 accumula-tion caused by carbonic anhydrase inhib-ition resulting in vasodilatation andincreased blood flow. This effect canbe hindered with the cyclo-oxygenaseinhibitor indometacine, indicating thatprostaglandin’s metabolism plays a rolein vasodilatation. The researchers havealso tried to develop non-invasive ret-inal oxymetry to study the optic in ret-inal oxygen metabolism in humans.

Another interesting programme inocular physiology involves the haemo-dynamics of retinal circulation.Researchers in Arhus have studied ret-inal vascular dynamics, in particularvasomotion, in an attempt to under-stand how vascular dynamics contrib-ute to the pathophysiology ofdiseases such as diabetic retinopathy(Bek 2002a; Hesellund 2002; Jeppesen2002). They observed vasomotion inretinal blood vessels and indicated thata disturbance in the dynamic propertiesof blood flow regulation may play arole in the pathophysiology of diabeticretinopathy.


561

Oculoplastic surgery

Just one paper in this field was pre-sented at the Tampere Meeting. Itcame from Rødahl & Mjanger (2002),of Bergen, who presented their series onsurgery on upper eyelid retraction inthyroid ophthalmopathy. They com-pared two previously described surgicalprocedures for treating upper eyelidretraction. The first comparisoninvolved the method described byMourits & Sasim (1999), where agraded disinsertion of the levator com-plex is performed, and the second con-cerned the approach developed byCollin & O’Donnell (1994), where acomplete separation of the levator com-plex is carried out and the eyelidsutures are adjusted the following dayif necessary. Rødahl & Mjanger (2002)recommend the latter approach asbeing superior to the first method.

Eyelid surgery in dysthyroid ophthal-mopathy was reviewed in the past byHedin (1988), who described a suture-less technique which achieves goodresults. Recently, Acta Ophthalmologicapublished two interesting papersdescribing orbital decompression insevere thyroid associated ophthalmo-pathy. The first of these, by Tallstedtet al. (2000), described using trans-antral orbital decompression. The sec-ond, by Linnet et al. (2001) referred tousing neurosurgical two-wall orbitaldecompression. This is mentioned herebecause ophthalmologists do notusually use these procedures; themajority instead use the orbitalapproach to achieve decompression ofthe orbital structures.

Oculoplastic surgery is a growingsubspecialty. There is an obvious needfor more research in this field in theNordic countries. Other subspecialtieshave formed their own Nordic societies.Scandinavian ophthalmologists inter-ested in oculoplastics have not yetdone so, but it may be a way of stimu-lating further development.

Ophthalmic oncology

Ophthalmic oncology maintains highand uniform standards in the Nordiccountries. This is due to a long tradi-tion of centralizing diagnosis and treat-ment of intraocular malignanttumours, generally high standards ofmedical care in the Nordic countries,

good medical statistics and a close con-nection between clinical ophthalmo-logical oncology and ophthalmicpathology. For many years, co-operationbetween the Nordic ophthalmo-oncological centres has increased bothon the practical clinical level and at amore basic scientific level.

At the NOK Meeting in Iceland in2000 this positive evolution was furthersupported by a series of sessions focus-ing on oncology, including an educa-tional course, a symposium and asession of free papers. This turned outto be a success, and the NOK 2002Board started a tradition by repeatingthe same oncology-focused series ofsessions. A more detailed descriptionis given below, but it should be statedagain that the success was obvious. Thetradition now seems firmly founded asa similar series of sessions will be heldat the forthcoming NOK 2004 meetingin Malmo.

The educational oncology course wasarranged by Tero Kivela, of Helsinki,who asked colleges from other Nordiccountries each to deal with an import-ant therapeutic or diagnostic problem.

The subject of when and how chor-oidal haemangioma should be treatedwas addressed by Eide (2002a), ofNorway.He described the various clinicalfeatures and demonstrated the positiveeffect of fractionated doses of externalbeam radiation. The modern, highlypromising photodynamic laser treat-ment was also presented.

The matter of what an ophthalmolo-gist managing glaucoma should knowabout uveal melanoma was discussedby Kivela (2002a). He stressed thatmalignant uveal melanoma may mimicany type of glaucoma and gave exam-ples to support the statement. His mostimportant message was: ‘Beware ofprogressive, unilateral glaucoma resist-ant to all types of treatment – alwayssuspect an occult tumour’.

Which conjunctival lesions should beremoved for diagnosis was explained byPrause (2002), of Denmark, who saidthat because most conjunctival lesionsare benign, biopsy of suspected cases isneeded. A good clinical history andexamination can guide the clinician.Anatomical characteristics are also ofgreat help. A useful diagnostic decisionalgorithm was presented.

The issue of which choroidal nevishould be sent for a second opinionwas addressed by Seregard (2002), of

Sweden. He pointed out that mostsmall, benign choroidal nevi maynever transform to malignant mela-noma. However, by clinical examina-tion it may be difficult to differentiatea nevus from a smallmelanoma. Seregardpointed out that for small, indeterminatelesions, five risk factors were of import-ance: tumour thickness >2mm, tumourtouching the optic disc, visual symptoms,orange pigment and subretinal fluid.Without any risk factor there seems tobe only a small (4%) risk of growth,while the presenceof three ormore factorsindicates a risk of over 50%. Such highlysuspicious lesions should be referred to anophthalmic oncology centre.

The scientific symposium ‘HotTopics in Ocular Oncology’ involvedthe presentation and discussion of animportant, new international paperdealing with aspects of ocular oncol-ogy, followed by a discussion of thepaper by a panel of Nordic ophthalmiconcologists.

Prause made a critical analysis of apaper by Shields et al. (2001) on con-junctival lymphoid tumours, whichincluded 117 consecutive patients fromthe period 1974–99. The strengths ofthe paper included the large number ofpatients and the long follow-up period.However, its weakness concerned thelack of a modern and complete histo-pathological analysis of the cases. Thetake-home message was that conjunc-tival lymphoid tumours are mostlyfound among elderly patients. Only aminor fraction of patients had or devel-oped systemic lymphoma and most ofthose had bilateral disease. MALTlymphoma is the dominating malignantlesion, and it has a favourable prognosis.

Eide (2002b) presented and discusseda report of 256 consecutive cases treatedby primary transpupillary thermo-therapy (TTT) for small (height 4mm)choroidal melanomas. A rather largeproportion of patients demonstratedrecurrence – the Kaplan�Meier esti-mate was 22% at 3years follow-up.The conclusion drawn from the analy-sis and the subsequent panel discussionwas that the Nordic use of TTT as anadjunctive treatment for tumoursotherwise irradiated seems justified.

Kivela (2002b) analysed and com-mented on the results of the Collabora-tive Ocular Melanoma Study’s(COMS) randomized trial of I125 bra-chytherapy for choroidal melanomaconcerning initial mortality. This


562

important study involved 1317 patientswith medium-sized melanomas from 43North American hospitals (COMSReport No. 18 (2001). The effect ofI125 brachytherapy on survival com-pared to that of enucleation wasanalysed. The main result of this studyand the analysis presented was thatthe mode of treatment of medium-sized choroidal melanoma doesnot significantly affect metastasis orsurvival.

Seregard critically reviewed the useof systemic chemotherapy for retino-blastoma confined to the globe. Duringrecent years, systemic chemotherapyhas evolved to become a popular first-line treatment for bilateral retinoblas-toma. External beam radiation has inthe same period been saved for salvagetherapy. Radiotherapy-related compli-cations in the form of mid-facial hypo-plasia and secondary malignantneoplasia seem to have been avoided.However, the chemotherapy treatmentrequires a multidisciplinary treatmentteam. The possible longterm risk ofchemotherapy remains unknown. Thepresentation inspired a positive discus-sion and pointed to the need for Nordicco-ordination of treatment criteria andpossibly, in the future, of centralizedtreatment.

The free paper session containedeight papers from three of the Nordiconcology centres, all of which gavea very positive impression of grow-ing scientific interest in ophthal-mic oncology and demonstrated theclose co-operative work between thecentres.

Bergman et al. (2002), of Stockholm,presented the paper ‘Incidence of uvealmelanoma in Sweden 1960–98’. Duringthe 39-year period, the age-standardizedincidence of uveal melanomadeclined in the male population, and asimilar trend was observed in thefemale population. Bergman et al.(2002) also presented an analysis of sur-vival rates in the same patient group.Based on data from 1539 males and1449 females, the excess mortality ratewas calculated for the first 10-yearperiod after diagnosis. The 5-yearsurvival rates were 57.1% for malesand 63.5% for females, while the10-year rates were 40.0% and 46.2%,respectively. The figures indicate thatthe diagnosis and treatment of uvealmelanoma in Sweden are up to the bestof international standards.

Eskelin & Pyrhonen (2002), ofHelsinki, presented a prognostic modeland staging for metastatic uveal mela-noma. Analysing data of 91 Finnish con-secutive patients who died of metastaticdisease in the period 1985–2000, and whohad participated in an annual review todetect metastases, they found a mediansurvival after detection of metastasis of8.4months. A number of clinical andlaboratory parameters were foundto have significant predictive value.Karnofsky index, largest diameter of larg-est metastasis and s-AP level wereindependent predictive parameters.Combining these parameters in rele-vant covariant combinations gave amodel for the categorization of patientsand seems to be a promising tool inpatient counselling and design of clin-ical trials.

Heegaard et al. (2002), of Copenhagen,described the establishment ofhuman uveal malignant melanomaxenotransplants in nude mice. Tissueblocks from human uveal melanomaswere transplanted to the flanks ofnude mice. In one of eight series, astable, transplantable tumour graft wasestablished. The histology of theserially transplanted tumour demon-strated that it retains the characteristicsof the original tumour. This new modelis easy to observe and access and mayform the basis for therapeutic experi-ments.

Also from Copenhagen, Alyahyaet al. (2002a) presented the biochemicalchanges of the sclera in melanoma-associated spongiform scleropathy andtheir possible relationship to scleralextension. By histochemical and bio-chemical analysis of melanoma eyeswith spongiform scleropathy it wasdemonstrated that this entity is asso-ciated with reduced collagen contentand a parallel increase in the contentof glycosaminoglycans in the sclera atthe site of the tumour. This may explainthe observation that spongiform sclero-pathy is present significantly more fre-quently in eyes with scleral tumourextension than in eyes without inva-sion.

On behalf of the Helsinki andCopenhagen groups, Alyahya et al.(2002b) also presented a joint study ofexfoliation syndrome based on a histo-pathological comparison of eyesremoved due to uveal melanoma andabsolute glaucoma. A total of 267 eyeswith malignant choroidal melanoma

and 344 eyes with absolute glaucomafrom the two countries were investi-gated for the presence of exfoliationmaterial. Exfoliation syndrome wasfound with the same frequency in mela-noma eyes in the two countries, whilethe syndrome was significantly less fre-quent in Danish eyes with absoluteglaucoma than in Finnish eyes. Differ-ent treatment strategies of glaucomatreatment between the two countriesmay partly explain this difference,which otherwise supports the clinicalobservation that pseudoexfoliation syn-drome is more common in Finlandthan in Denmark.

Sjo et al. (2002a), of the Copenhagengroup in co-operation with the humanpapilloma virus (HVP) group from theInstitute Pasteur, then presented astudy of lacrimal sac tumours andHPV. Five papillomas and six carcin-omas of the lacrimal sac were analysedfor the presence of HPV using polymer-ase chain reaction (PCR) techniquetogether with DNA and mRNA in situhybridization. A strong associationbetween HPV and the two rare tumourtypes was found, indicating a role forHPV in tumour induction.

The same group closed the stimulat-ing session by presenting their studiesof HPV and epithelial tumours of thehuman conjunctiva (Sjo et al. 2002b). Atotal of 168 papillomas, 14 conjunctivalcarcinoma in situ and 19 frank conjunc-tival carcinomas were analysed usingthe same techniques applied in thestudy above. In all, 80% of the papil-lomas, 33% of the carcinoma in situ butonly 8% of the invasive carcinomasharboured HPV. The findings indicatean important role of HPV in papillomainduction, but do not explain the roleof HPV in the development of carcin-oma.

Conclusion

While this review by no means repre-sents a comprehensive overview of allthe research in vision and ophthalmol-ogy that goes on in the Nordic coun-tries, it does give an impression of thevaried and extensive research work thatis taking place. Nordic scientists arecontributing to world ophthalmicresearch and literature in a significantway, and are at the cutting edge ofscience in several fields. This is notan insignificant accomplishment by a


563

combined population of only 25 million.The impact of Nordic ophthalmologyon a world scale may be better recog-nized by ophthalmologists around theworld than by the local medical com-munity and population. It is hoped thatthis review and similar papers to followwill help demonstrate the magnitude ofNordic research in vision and ophthal-mology and its impact on medicalscience.

ReferencesAdolph AR (1994): Function and structure in

retinal transplants. J Neural Transplant

Plast 5: 147–161.

Agardh E (2002): Will I be able to see my child?

Acta Ophthalmol Scand 80: 409.

Airaksinen PJ (2002): Indications for tube

shunt surgery. Acta Ophthalmol Scand 80:

414.

Algvere PV, Berglin L, Gouras P & Sheng Y

(1994): Transplantation of fetal retinal pig-

ment epithelium in age-related macular

degeneration with subfoveal neovasculariza-

tion. Graefes Arch Clin Exp Ophthalmol

232: 707–716.

Algvere PV, Gouras P & Dafgard Kopp E

(1999): Longterm outcome of RPE allografts

in non-immunosuppressed patients with

AMD. Eur J Ophthalmol 9: 217–230.

Algvere PV, Gouras P, Sheng Y & Kopp ED

(1997): Transplantation of RPE in age-

related macular degeneration: observations

in disciform lesions and dry RPE atrophy.

Eur J Ophthalmol 9: 217–230.

Algvere PV, Lindgarde G & Seregard S (2002):

Transpupillary thermotherapy for occult

choroidal neovascularization (CNV) in age-

related macular degeneration (AMD). Acta

Ophthalmol Scand 80: 416.

Alm A (2002a): From prostaglandin F2a to

latanoprost. Acta Ophthalmol Scand 80:

458.

Alm A (2002b): Safety of latanoprost. Acta


Alyahya GA, Hietanen J, Heegaard S,

Prause JU & Kivela T (2002b): Exfoliation

syndrome in Denmark and Finland. A histo-

pathological comparison of eyes removed

because of uveal melanoma and absolute

glaucoma. Acta Ophthalmol Scand 80: 682.

Alyahya GA, Ribel-Madsen SM, Heegaard S,

Prause JU & Trier K (2002a): The biochem-

ical changes of the sclera in melanoma-

associated spongiform scleropathy and pos-

sible relation to scleral extension. Acta


Andersen N (2002): Age-related macular

degeneration among Inuit in Greenland.


Aramant R, Seiler M, Ehinger B, Bergstrom A,

Adolph AR & Turner JE (1990): Neuronal

markers in rat retinal grafts. Brain Res Dev

Brain Res 53: 47–61.

Aramant R, Seiler M & Turner JE (1988):

Donor age influences on the success of

retinal grafts to adult rat retina. Invest

Ophthalmol Vis Sci 29: 498–503.

Bek T (2002a): Dynamic changes in lesions

caused by retinal vascular disease. Acta


Bek T (2002b): Telescreening for diabetic retino-

pathy. Acta Ophthalmol Scand 80: 432.

Bengtsson B (2002): Evaluation of VEP peri-

metry in normal subjects and glaucoma

patients. Acta Ophthalmol Scand 80: 620–

626.

Bengtsson B (2003): A new rapid threshold

algorithm for short-wavelength automated

perimetry. Invest Ophthalmol Vis Sci 44:

11388–11394.

Bengtsson B & Heijl A (1998a): Evaluation of a

new perimetric threshold strategy, SITA, in

patients with manifest and suspect glau-

coma. Acta Ophthalmol Scand 76: 268–272.

Bengtsson B & Heijl A (1998b): SITA Fast, a

new rapid perimetric threshold test. Descrip-

tion of methods and evaluation in patients

with manifest and suspect glaucoma. Acta

Ophthalmol Scand 76: 431–437.

Bengtsson B, Olsson J, Heijl A & Rootzen H

(1997): A new generation of algorithms for

computerized threshold perimetry, SITA.

Acta Ophthalmol Scand 75: 368–375.

Bergman L, Seregard S, Nilsson B, Ringborg U,

Lundell G & Ragnarsson-Olding B (2002):

Incidence of uveal melanoma in Sweden

1960–98. Acta Ophthalmol Scand 80: 680.

Bergstrom A, Ehinger B, Wilke K, Zucker CL,

Adolph AR & Szel A (1994): Development

of cell markers in subretinal rabbit retinal

transplants. Exp Eye Res 58: 301–313.

Collin JR & O’Donnell BA (1994): Adjustable

sutures in eyelid surgery for ptosis and lid

retraction. [Comment.] Br J Ophthalmol 78:

167–174.

Corydon L, Dam-Johansen M & Olsen T

(2002a): Astigmatism after cataract surgery.


Corydon L, Dam-Johansen M & Olsen T

(2002b): Contrast sensitivity with the Phar-

macia Tecnis Z9000 intraocular lens. Acta


la Cour M, Kiilgaard JF & Nissen MH (2002):

Age-related macular degeneration: epide-

miology and optimal treatment. Drugs

Aging 19: 101–133.

Crafoord S (2002): Submacular surgery update.

[Abstract.] Acta Ophthalmol Scand 80: 416.

Crafoord S, Algvere PV, Kopp ED & Seregard S

(2000a): Cyclosporine treatment of RPE

allografts in the rabbit subretinal space. Acta


Crafoord S, Algvere PV, Seregard S &

Kopp ED (1999): Longterm outcome of

RPE allografts to the subretinal space of

rabbits. Acta Ophthalmol Scand 77: 247–254.

Crafoord S, Dafgard Kopp E, Seregard S &

Algvere PV (2000b): Cellular migration into

neural retina following implantation of mel-

anin granules in the subretinal space.

Graefes Arch for Clin Exp Ophthalmol

238: 682–689.

Crafoord S, Geng L, Seregard S & Algvere PV

(2001): Experimental transplantation of

autologous iris pigment epithelial cells to

the subretinal space. Acta Ophthalmol

Scand 79: 509–514.

Dinparvar D, HaugenOH&Reigstad H (2002):

An epidemiological study on retinopathy of

prematurity in a Norwegian county. Acta


Ehinger B, Bergstrom A, Seiler M, Aramant RB,

Zucker CL, Gustavii B & Adolph AR (1991):

Ultrastructure of human retinal cell transplants

with long survival times in rats. ExpEyeRes 53:

447–460.

Eide N (2002a): When and how should chor-

oidal haemangioma be treated? Acta


Eide N (2002b): Primary transpupillary thermo-

therapy for small choroidal melanoma. A

critical review. Acta Ophthalmol Scand 80:

413.

Eskelin S & Pyrhonen S (2002): A prognostic

model and staging for metastatic uveal

melanoma. Acta Ophthalmol Scand 80: 681.

Eysteinsson T, Jonasson F, Sasaki H,

Arnarsson A, Sverrisson T, Sasaki K &

Stefansson E (2002): Central corneal thick-

ness, radius of the corneal curvature and

intraocular pressure in normal subjects using

non-contact techniques; The Reykjavik Eye

Study. Acta Ophthalmol Scand 80: 11–15.

Fagerholm P (2002): Corneal wound healing: a

multitude of aspects. Acta Ophthalmol

Scand 80: 431.

Floren I, Skarin A & Myers A (2002): Three

cases of acanthamoeba keratitis in 3 months.


Frennesson C & Nilsson SEG (2002): Prophy-

lactic laser to drusen. An update. Acta


Ghosh F & Arner K (2002): Transplantation of

full-thickness retina in the normal porcine

eye: surgical and morphologic aspects.

Retina 22: 478–486.

Ghosh F, Arner K & Ehinger B (1998): Trans-

plant of full-thickness embryonic rabbit

retina using pars plana vitrectomy. Retina

18: 136–142.

Ghosh F, BruunA&Ehinger B (1999a): Graft�host connections in longterm full-thickness

embryonic rabbit retinal transplants. Invest

Ophthalmol Visual Sci 40: 126–132.

Ghosh F, Bruun A & Ehinger B (1999b):

Immunohistochemical markers in full-

thickness embryonic rabbit retinal transplants.

Ophthalmic Res 31: 5–15.

Ghosh F, Johansson K & Ehinger B (1999c):

Longterm full-thickness embryonic rabbit

retinal transplants. Invest Ophthalmol

Visual Sci 40: 133–142.

Grødum K, Heijl A & Bengtsson B (2002a):

Which glaucoma patients are missed and

does it matter? Acta Ophthalmol Scand 80:

680.

Grødum K, Heijl A & Bengtsson B (2002b): A

comparison of glaucoma patients identified

through mass screening and in routine clin-

ical practice. Acta Ophthalmol Scand 80:

627–631.


564

Haugen OH (2002): Visual disorders related to

Down’s syndrome. Acta Ophthalmol Scand

80: 433.

Haugen OH, Hovding G & Lundstrom I (2001):

Refractive development in children with

Down’s syndrome: a population-based,

longitudinal study. Br J Ophthalmol 85:

714–719.

Hedin A (1988): Eyelid surgery in dysthyroid

ophthalmopathy. Eye 2: 201–206.

Heegaard S, Spang-Thomsen M, Prause JU

(2002): Establishment of human uveal malig-

nant melanoma xenotransplants in nude

mice. Acta Ophthalmol Scand 80: 681

Hesellund A (2002): Characterization of retinal

vasomotion in vitro. Acta Ophthalmol

Scand 80: 425.

Hietanen J & Kivela T (2002): Is exfoliation

syndrome a systemic disease? Acta Ophthal-

mol Scand 80: 417.

Hietanen J, Soissalon-Soininen S, Kivela T &

Tarkkanen A (2002): Evaluation of the clin-

ical association between exfoliation syn-

drome and abdominal aortic aneursym.


Holm O (2002): Contrast enhancement of

fundus images. Acta Ophthalmol Scand 80:

431.

Holmstrom G, Azazi M, Jacobson L, Sachs D,

Sule J & Lennerstrand G (1993): Epidemiol-

ogy of ROP in the Stockholm area of

Sweden. Acta Ophthalmol Scand 80 (Suppl):

44–47.

Hjortdal (2002): Customized refractive ablation

of the cornea. Acta Ophthalmol Scand 80:

XXXV Nordic meeting abstract book p. 60.

JacobsonL,HellstromA,FlodmarkO,MartinL&

Ygge J (2002a): Visual function, eye motility

and optic disc appearance in cerebral visual

impairment. Acta Ophthalmol Scand 80: 433.

Jacobson L, Ygge J, Flodmark O & Ek U

(2002b): Visual and perceptual characteris-

tics, ocular motility and strabismus in

children with periventricular leukomalacia.

Strabismus 10: 179–183.

Jakobsen JE (2002): Circuital trabeculotomy

for developmental glaucoma. Acta Ophthal-

mol Scand 80: 407.

Jensen PK (2002): Digital fundus photography.


Jensen PK, Eysteinsson T, PedersenDB, BangK,

Beach J & Stefansson E (2002): Non-invasive

retinal oxymetry in normal human subjects.


Jeppesen P (2002): Measurement of dynamic

changes in retinal vascular diameter in vivo.


Jonasson F, Ning-Pu L, Vance JM,

Dew-Knight S, Reyner M, Akama TO,

Fukuda MN & Klintworth GK (2002a):

Mutation in corneal carbohydrate sulfo-

transferase 6 (SHST6) gene causes macular

corneal dystrophy in Iceland.ActaOphthalmol

Scand 80: 430.

Jonasson F, Sverrisson T & Arnarsson A et al.

(2002b): The prevalence of age-related

maculopathy in Iceland. The Reykjavik Eye

Study. Acta Ophthalmol Scand 80: 682.

Juliusson B, Bergstrom A, van Veen T &

Ehinger B (1993): Cellular organization in

retinal transplants using cell suspensions or

fragments of embryonic retinal tissue. Cell

Transplant 2: 411–418.

Juliusson B, Mieziewska K, Bergstrom A,

Wilke K, Van Veen T & Ehinger B (1994):

Interphotoreceptor matrix components in

retinal cell transplants. Exp Eye Res 58:

615–621.

Kiilgaard JF, Scherfig E, KlassenH,WarfingeK,

Prause JU & Young MJ (2003): Trans-

plantation of xenogeneic retinal stem cells

to pig subretinal space. [ARVO Abstract

A483.] Invest Ophthalmol Vis Sci 80: 681.

Kiilgaard JF, Scherfig E, la Cour M &

Prause JU (2002a): Prevention of choroidal

neovascularization by transplantation of the

amniotic membrane to the subretinal space

in pigs. [Abstract.] Acta Ophthalmol Scand

80: 443.

Kiilgaard JF, Wiencke AK, Scherfig E,

Prause JU & la Cour M (2002b): Transplan-

tation of the allogenic anterior lens capsule

to the subretinal space in pigs. Acta


Kivela T (2002a): What should an ophthal-

mologist managing glaucoma know about

uveal melanoma? Acta Ophthalmol Scand

80: 456.

Kivela T (2002b): Collaborative Ocular Mela-

noma Study (COMS) randomized trial of

iodine-125 brachytherapy for choroidal mel-

anoma: initial mortality findings. A critical

review. Acta Ophthalmol Scand 80: 413.

Koivula A & Zetterstrom C (2002): Scleral

fixated capsular tension ring and IOL in

the bag in patients with ectopia lentis. Acta


Kugelberg U & Magnusson G (2002): Screen-

ing for congenital cataract in Sweden. Acta


Kugelberg M, Shafiei K & Zetterstrom C

(2002): Topical treatment with dexametha-

sone inhibits growth in the newborn rabbit.


Kugelberg M & Zetterstrom C (2002): Up to

what age should paediatric cataract surgery

be performed with anterior vitrectomy? Acta


Larsen M (2002a): Arterial hypertension and

other factors of importance for the course of

diabetic retinopathy. Acta Ophthalmol

Scand 80: 415.

Larsen M (2002b): Assessment of the perform-

ance of automated fundus photography

analysis in diabetic retinopathy screening.


Larsen M (2002c): Overlapping characteristics

of diabetic retinopathy and branch retinal

vein occlusion. Acta Ophthalmol Scand 80:

426.

Larsson LI (2002): Efficacy of Xalcom in

glaucoma treatment. Acta Ophthalmol

Scand 80: 458.

Larsson E, Carle-Petrelius BF, Cernerud G,

Ots L, Wallin A & Holmstrom G (2002):

Incidence of ROP in two consecutive

Swedish population-based studies. Br J

Ophthalmol 86: 1122–1126.

Larsson J, Juliusson B & Ehinger B (1998):

Survival and MHC-expression of embryonic

retinal transplants in the choroid. Acta


Linnet J, Hegedus L & Bjerre P (2001): Results

of a neurosurgical two-wall orbital decom-

pression in the treatment of severe thyroid

associated ophthalmopathy. Acta Ophthal-

mol Scand 79: 49–52.

Lundstrom M (2002): Aspects of cataract sur-

gery and quality of life: an analysis of 10 000

completed Catquest questionnaires. Acta


Lundvall A & Kugleberg U (2002): Outcome of

treatment of congenital unilateral cataract.


Lundvall A & Zetterstrom C (2002): Outcome

after treatment of congenital cataract. Acta


Makinen P, Pietila J & Uusitalo H (2002):

Photorefractive keratectomy (PRK) for

myopia: 8 years follow-up. Acta Ophthalmol

Scand 80: 421.

Mika H (2002): Conversion of ocular hypoten-

sion to capsular glaucoma and progression

of capsule glaucoma. Acta Ophthalmol

Scand 80: 417.

Møller Pedersen T (2002): Confocal micro-

scopic imaging of the cornea.ActaOphthalmol

Scand 80: 430.

Montan P (2002): Post-operative endophthal-

mitis following cataract surgery in Sweden:

national and single centre incidence data and

their relationship to prophylaxis. Acta


Mourits MP & Sasim IV (1999): A single

technique to correct various degrees of

upper lid retraction in patients with Graves’

orbitopathy. Br J Ophthalmol 83: 81–84.

Narfstrom K, Katz ML & Bragadottir R et al.

(2003a): Functional and structural recovery

of the retina after gene therapy in the RPE65

null mutation dog. Invest Ophthalmol

Visual Sci 44: 1663–1672.

Narfstrom K, Katz ML, Ford M, Redmond

TM, Rakoczy PE & Bragadottir R (2003b):

In vivo gene therapy in young and adult

RPE65-/- dogs produces longterm visual

improvement. J Hered 94: 31–37.

Nicolini J, Kiilgaard JF, Wiencke AK,

Heegaard S, Scherfig E, Prause JU &

la Cour M (2000): The anterior lens capsule

used as support material in RPE cell-

transplantation. Acta Ophthalmol Scand 78:

527–531.

Nilson SEG, Sundelin S, Wihlmark U,

Roberg K & Brunk U (2002): Oxidative

reactions in the retinal pigment epithelium,

antioxidants and age-related macular

degeneration. Acta Ophthalmol Scand

80: 415.

Ohrstrom A, Svensson B, Celadet C, Tegenfeldt S

&Lignell B (2002):Thevisco-silicon connection.


Pedersen DB, Kiilgaard JF, Jensen PK,

Eysteinsson T, la Cour M, Bang K &

Stefansson E (2002): Carbonic anhydrase

inhibitors and optic nerve oxygen tension.


Prause JU (2002): Which conjunctival lesions

should be removed for diagnosis? Acta



565

Puska PM (2002): Unilateral exfoliation syn-

drome: conversion to bilateral exfoliation and

to glaucoma. A prospective 10-year follow-up

study. Acta Ophthalmol Scand 80: 417.

Rødahl E & Mjanger Ø (2002): Surgery for

upper eyelid retraction in thyroid eye syn-

drome. Acta Ophthalmol Scand 81: 684.

Rosenberg ME, Tervo TMT, Muller LJ,

Moilanen AO & Vesaluoma MH (2002): In

vivo confocal microscopy after herpes kera-

titis. Cornea 21: 265–269.

Seregard S (2002): Which choroidal nevi

should be sent for second opinion? Acta


Sharma RK, Bergstrom A & Ehinger B (1997):

Influence of technique and transplantation site

on rosette formation in rabbit retinal

transplants. ActaOphthalmol Scand 75: 3–10.

Sharma RK, Bergstrom A, Zucker CL, Adolph

AR & Ehinger B (2000): Survival of long-

term retinal cell transplants. Acta Ophthal-

mol Scand 78: 396–402.

Sharma RK & Ehinger B (1997a): Cell

proliferation in retinal transplants. Cell

Transplant 6: 141–148.

Sharma RK & Ehinger B (1997b): Mitosis in

developing rabbit retina: an immunohisto-

chemical study. Exp Eye Res 64: 97–106.

ShatosMA, KlassenH, Scherfig E, Kiilgaard JF,

Warfinge K, Prause JU & Young MJ (2003):

Isolation, characterization and expansion of

porcine retinal progenitor cells. [ARVO

Abstract A1694.] Invest Ophthalmol Vis Sci

44.

Shields CL, Shields JA, Carvalho C, Rundle P

& Smith AF (2001): Conjunctival lymphoid

tumours: clinical analysis of 117 cases and

relationship to systemic lymphoma.

Ophthalmology 108: 979–984.

Sirpa L & Risto K (2002): Perimacular

microcirculatory flow velocity during type 1

diabetic pregnancy and the early postpartum

period. Acta Ophthalmol Scand 80: 445.

Sjo NC, Lindeberg H,Heegaard S, Buchwald C,

Prause JU, Flamant P & Orth G (2002a):

Lacrimal sac tumours and human papillo-

mavirus. Acta Ophthalmol Scand 80: 681.

Sjo NC, Lindeberg H,Heegaard S, Buchwald C,

Prause JU, Flamant P & Orth G (2002b):

Epithelial tumours of the conjunctiva and

human papillomavirus. Acta Ophthalmol

Scand 80: 681.

Sjølie AK (2002): Retinoprotection: newmethods

of altering the development and progression of

retinopathy. Acta Ophthalmol Scand 80: 409.

Stefansson E (2001): The therapeutic effects of

retinal laser treatment and vitrectomy. A

theory based on oxygen and vascular

physiology. Acta Ophthalmol Scand 79:

435–440.

Stefansson E (2002): Diabetic retinopathy

and the mechanism of treatment. Acta


Stefansson E, Bek T, Porta M, Larsen N,

Kristinsson JK & Agardh E (2000): Screen-

ing and prevention of diabetic blindness.


Stefansson E, Pedersen DB & Kiilgaard JF

et al. (2002): Optic nerve oxygen metabolism

and carbonic anhydrase inhibitors: an

overview. Acta Ophthalmol Scand 80: 424.

Stenevi U, Hanson F, Claesson M,

Roneliusson E & Ek S (2002): Survival of

transplanted human corneal stem cells. Case

Report. Acta Ophthalmol Scand 80: 105–108.

Tallstedt L, Papatziamos G, Lundblad L &

Anggard A (2000): Results of transantral

orbital decompression in patients with

thyroid-associated ophthalmopathy. Acta


Thygesen J (2002): Prostaglandin F2a propertiesin travoprost and other prostaglandin deriva-

tives: clinical aspects. Acta Ophthalmol Scand

80: 459.

Thygesen J & Kessing SV (2002): Congenital

glaucomas: 25 years of experience. Acta


Uusitalo R, Sen N & Laatikainen L (2002):

Quality of vision in patients with monofocal

or multifocal intraocular lenses. Acta


Valimaki J (2002): Problems related to glaucoma

drainage implant surgery. Acta Ophthalmol

Scand 80: 414.

Veske A, Nilsson SE, Narfstrom K & Gal A

(1999): Retinal dystrophy of Swedish briard/

briard-beagle dogs is due to a 4-bp deletion

in RPE65. Genomics 57: 57–61.

Virtamo T, Summanen PA, Hyttinen VT,

Tuomilehto J, Jaakko OI & Laatikainen LT

(2002): Diabetic retinopathy and visual

impairment in juvenile onset diabetic

patients in Finland. Acta Ophthalmol

Scand 80: 452.

VonWendtGC,Heikkala KV& Summanen PA

(2002): Detection of retinal neovascular-

izations using 45� and 60� photographic

fields: varying 45� fields simulated on 60�

photographs. Acta Ophthalmol Scand 80:

453.

Vuori ML (2002): Glaucoma implant surgery

for complicated glaucoma cases. Acta


Warfinge K, Kiilgaard JF, Larvik E, Klassen H,

Scherfig E, Langer R & Young MJ (2003):

Survival, integration and differentiation of

retinal progenitor cells from GFP transgenic

mice transplanted subretinally to adult,

normal pigs. [ARVO Abstract A483.] Invest

Ophthalmol Vis Sci.

Wasselius J & Ghosh F (2001): Adult rabbit

retinal transplants. Invest Ophthalmol Vis

Sci 42: 2632–2638.

Wejde G (2002): Postoperative endophthalmi-

tis following cataract surgery: risk factor

analysis based on retrospective single centre

data. Acta Ophthalmol Scand 80: 426.

Wiencke AK, Kiilgaard JF, Nicolini J, Bund-

gaard M, Ropke C & la Cour M (2003):

Growth of cultured porcine retinal pigment

epithelial cells. Acta Ophthalmol Scand 81:

170–176.

Zetterstrom C (2002): IOL implantation in the

newborn eye. Acta Ophthalmol Scand 80:

420.

Zhang Y, Arner K, Ehinger B & Perez MT

(2003): Limitation of anatomical integration

between subretinal transplants and the host

retina. Invest Ophthalmol Vis Sci 44: 324–

331.

Zhang Y, Sharma RK, Ehinger B & Perez MT

(1999): Nitric oxide-producing cells project

from retinal grafts to the inner plexiform

layer of the host retina. Invest Ophthalmol

Vis Sci 40: 3062–3066.

Zucker CL, Ehinger B, Seiler M, Aramant RB

& Adolph AR (1994): Ultrastructural circui-

try in retinal cell transplants to rat retina. J

Neural Transplant Plast 5: 17–29.

Received on July 10th, 2003.

Accepted on August 20th, 2003.

Correspondence:

Einar Stefansson MD

University of Iceland

Landspıtali-haskolasjukrahus

Augndeild

101 Reykjavık

Iceland

Tel:þ 354 543 7217

Fax:þ 354 543 4831

Email: [email protected]


566

Documents

Nordic research in ophthalmology