Fluoreskeiiniangiografia (FA) kostean silmänpohjan ikärappeuman diagnostiikassa

Tanja Laukkala

Näytön aste: C

Fluoreskeiiniangiografia (FA) on ilmeisesti edelleen kostean silmänpohjan ikärappeuman diagnostiikan kulmakivi valokerroskuvaukseen (OCT-tutkimus) verrattuna, ellei tutkimuksen suorittamiselle ole terveydellisiä esteitä.

Flureskeiiniangiografiatutkimuksessa verisuoneen ruiskutettu väriaine kulkeutuu verenkierron mukana verkkokalvolle, ja verkkokalvon alle kasvaneista uudissuonista tihkuva tai verkkokalvon turvotusalueille kertyvä väriaine on keskeinen poikkeava löydös kostessa silmänpohjarappeumassa.

The aim of the systematic review «Mowatt G, Hernández R, Castillo M ym. Optical cohe...»1 was to determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected neovascular age-related macular degeneration (nAMD) and in monitoring those previously diagnosed with the disease.

Electronic databases searched included MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Bioscience Information Service, Science Citation Index, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Medion, Health Technology Assessment database, PsycINFO, Applied Social Sciences Index and Abstracts, conference abstracts from the American Academy of Ophthalmology, the Association for Research in Vision and Ophthalmology, the European Association for Vision and Eye Research and current research registers. Searches were carried out from 1995 to March 2013 other than for conference abstracts (2009 to November 2012).

Types of studies considered included direct or indirect comparisons reporting diagnostic outcomes. The population was people with newly suspected nAMD or those previously diagnosed with the disease and under surveillance monitoring. The index test was TD-OCT or SD-OCT and comparator tests considered were clinical evaluation, visual acuity (VA), Amsler grid, colour fundus photographs, infrared reflectance, red-free images or blue reflectance, fundus autofluorescence (FAF) imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry (PHP) and microperimetry. The reference standard was FA. Two reviewers independently screened the titles and abstracts of all reports identified by the search strategy and full-text papers were obtained for assessment. Data extraction was undertaken by one reviewer and checked by a second. Two reviewers independently assessed the risk of bias of the studies using the quality assessment of diagnostic accuracy studies, version 2 instrument.

Altogether 22 diagnostic studies with 2124 patients were included in the systematic review. 21 studies reported eyes as an unit of analysis (number of eyes 1754) and one study reported that 155 patients were included. 45.4% (N=742) were male. Age: median 76.0 years (range 51.4–84.6).

Tests reported in the included diagnostic studies; OCT 13 studies (N=1335); TS –OCT 12 studies and SD-OCT 1 (N=19), ICGA 8 studies (N=458), PHP three studies (N=491) and FP (N=185), Amsler grid (N=98) and FAF one study (N=62).

Four studies, all TD-OCT, reported both sensitivity and specificity, providing sufficient data for inclusion in a meta-analysis.The pooled sensitivity and specificity (95%CI) was 88% (46% to 98%) and 78% (64% to 88%), LR+ was 4.08 (95% confidence interval 2.37 to 7.04), LR - 0.15 (95% confidence interval 0.02–0.98) and DOR 26.86 (95% confidence interval 3.36–214.81).

In descriptive analyses, median sensitivity was high for ICGA (93.2 %, range 84.6–100.0 %; four studies) and FAF (93.3 %; one study), followed by PHP (81.5 %, range 50.0–84.8 %; three studies), colour fundus photography (70.0 %; one study) and lowest for Amsler grid (41.7 %; one study). Specificity was highest for colour fundus photography (95 %; one study), followed by PHP (84.6 %and 87.7 %; two studies), and was low for FAF (37.1 %; one study) and ICGA (36.8 %;one study).

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Kommentti: Katsauksen laatijoiden mukaan tutkimuksissa oli heterogeenisyyttä ja erityisesti potilasvalinnassa harhan riski.

The aim of this HTA report written in German with an English abstract «Stürzlinger H, Genser D, Fröschl B. Evaluation of ...»2 was to investigate the efficacy as well as (economic) efficiency of OCT compared to FA in the diagnostics of AMD. A systematic literature search was performed in 34 international databases which yielded 2324 articles. Following a two-part selection process according to predefined selection criteria only eight medical publications remained for inclusion for assessment. According to the defined criteria the quality of the studies was low except for one study. The number of investigated patients was below 35 in four publications, between 35 and 61 in three studies, and above 100 in only one publication. The study with the highest quality evaluated the diagnostic accuracy of OCT compared to FA in 131 eyes of 118 patients suspected of having choroidal neovascularisation. For OCT the sensitivity for detecting new potentially treatable lesions (84 eyes with classic or occult choroidal neovascularisation or serous pigment epithelial detachment) was 96% and the specificity was 66%. Including stereo colour images led to a sensitivity of 94% and a specificity of 89%. The authors conclude that OCT cannot replace the gold standard FA during the primary diagnostic procedure. OCT yields diagnostic findings in addition to FA results, unclear findings of FA can be clarified and in certain cases OCT can possibly replace FA. No recommendation was made from the economic point of view, as no economic assessments were available. In the studies published so far older models of OCT had been used and using newer models might change the findings for some classes or stages of AMD.

  • Tutkimuksen laatu: heikko
  • Sovellettavuus suomalaiseen väestöön: hyvä

Kommentti: Laatuarvio perustuu HTA-katsauksen englanninkieliseen abstraktiin. Rajausta kostean silmänpohjarappeuman diagnostiikkaan ei ole mainittu abstraktissa.

According to European Society of Retina Specialists (EURETINA) guideline «Schmidt-Erfurth U, Chong V, Loewenstein A ym. Guid...»3 fluorescein angiography (FA) is the only diagnostic examination that can confirm the mere existence of a CNV and if not contraindicated for systemic risks is routinely mandatory.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

Kommentti: Yleinen, väittämään liittyvä kommentti. Kirjallisuudessa kuvattu anafylaktinen reaktio fluoreskeiiniväriaineelle on este uusintatutkimukselle samalla väriaineella.

The aim of this retrospective UK study was to evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) for neovascular age-related macular degeneration, nAMD «Wilde C, Patel M, Lakshmanan A ym. The diagnostic ...»4. A retrospective review of all SD-OCT, colour fundus photographs (FP) and fundus fluorescein angiography (FA) pf 411 consecutive patients (822) eyes that were referred to rapid access Macular Clinic from February 2009 to February 2013. Inclusion criteria were all patients over 50 years of age that were referred for suspected nAMD by optometrists, general practitioners or other ophthalmologists and had symptoms of reduced vision, metamorphopsia, or signs suggestive of nAMD as determined by referring clinician. Also patients who may have had treatment 6 or more months previously with verteporfin photodynamic therapy or antiVEGF but were thought to have new CNV lesions were included. A small number of individuals may have been myopic and these were not excluded from the analysis. Exclusion criteria included all patients that had either no SD-OCT or FP/FA available for analysis or those patients where one imaging modelity was deemed ungradable. In addition, if the SD-OCT or FA were not performed within 7 days of each other the patient was excluded. Patients with CNV secundary to angioid streaks or evidence of chorioretinitis were excluded.

278 eyes were graded as having CNV with OCT, and had both gradable FA and SD-OCT. Within this group the mean age was 80.6 years (range 51–97) and 115 were male and 163 female. All SD-OCT images were graded by at least two ophthalmologists and if there was disagreement then adjudication by a third ophthalmologist took place. After the assignment of the SD-OCT grade the patient's mydriatic colour FP was reviewed. FA images were graded as classic, predominantly classic, minimally classic, occult, disciform scar, peripapillary CNV, no CNV, or other pathology. CNV was considered present if classic or occult leakage was detected. With SD-OCT CNV was considered present with the grading of changes at the level of inner choroid the RPE or retina, also shown by pictures in the study. There were a total of 47 false positives with SD-OCT (16.9%), seven of these were diagnosed as disciform scars (inactive chronic CNV scars). Reference to FP did not change any of SD-OCT grades. One false negative was present. The sensitivity and specifity of SD-OCT alone for detecting CNV was 100% and 80.8%. The authors conclude that SD-OCT is highly sensitive in detecting nAMD but specifity and false-positive rates compared to FA are currently unacceptable.

  • Tutkimuksen laatu: heikko
  • Sovellettavuus suomalaiseen väestöön: hyvä


  1. Mowatt G, Hernández R, Castillo M ym. Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration: a systematic review and economic evaluation. Health Technol Assess 2014;18:1-254 «PMID: 25436855»PubMed
  2. Stürzlinger H, Genser D, Fröschl B. Evaluation of optical coherence tomography in the diagnosis of age related macula degeneration compared with fluorescence angiography. GMS Health Technol Assess 2007;3:Doc02 «PMID: 21289936»PubMed
  3. Schmidt-Erfurth U, Chong V, Loewenstein A ym. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol 2014;98:1144-67 «PMID: 25136079»PubMed
  4. Wilde C, Patel M, Lakshmanan A ym. The diagnostic accuracy of spectral-domain optical coherence tomography for neovascular age-related macular degeneration: a comparison with fundus fluorescein angiography. Eye (Lond) 2015;29:602-9; quiz 610 «PMID: 25907206»PubMed