PMID- 30903310 OWN - NLM STAT- MEDLINE DCOM- 20190605 LR - 20240109 IS - 1435-702X (Electronic) IS - 0721-832X (Linking) VI - 257 IP - 6 DP - 2019 Jun TI - The absence of fundus abnormalities in Stargardt disease. PG - 1147-1157 LID - 10.1007/s00417-019-04280-8 [doi] AB - PURPOSE: To raise awareness of Stargardt disease (STGD1) patients without fundus abnormalities. METHODS: Medical records were evaluated for age at onset, initial symptoms and diagnosis, reason for delay of diagnosis, age at STGD1 diagnosis, best-corrected visual acuity (BCVA), ophthalmoscopy, fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), color vision test, and the presence of ABCA4 variants. RESULTS: In 11.1% of our STGD1 cohort of 280 patients, no fundus abnormalities were observed at first ophthalmic consultation. The median age at onset was 8 years (range, 1-18). There was a median delay in diagnosis of 3 years (range, 0-19) in 27 out of 31 patients, which resulted in a median age at diagnosis of 12 years (range, 7-26). Patients were misdiagnosed with amblyopia, myopia, optic disk pathology, mental health problems, tension headache, neuritis bulbaris, and uveitis. Subtle abnormalities, such as lipofuscin accumulation, were seen on FAF at an earlier disease stage than in ophthalmoscopy. On SD-OCT, this included a thickened external limiting membrane. Color vision tests showed red-green insufficiency in 79% of patients. Reduced ERG amplitudes were only present in 26% (N = 8) and a dark choroid sign in 65% of the patients. Visual acuity considerably fluctuated in the first 5 years after onset. The majority of the patients (65%) carried a least one variant with a severe effect on ABCA4 function. CONCLUSIONS: Childhood-onset STGD1 patients were diagnosed with a delay of median 3 years. The presence of accurate competence, equipment, and the possibility for genetic screening is required; therefore, we recommend to refer children with visual complaints without initial fundus abnormalities to a specialized ophthalmologic center. In particular, to diagnose patients at an early stage of disease is of increased importance with the advent of new therapeutic possibilities. FAU - Bax, Nathalie M AU - Bax NM AD - Department of Ophthalmology (400), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. FAU - Lambertus, Stanley AU - Lambertus S AD - Department of Ophthalmology (400), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. FAU - Cremers, Frans P M AU - Cremers FPM AD - Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. FAU - Klevering, B Jeroen AU - Klevering BJ AD - Department of Ophthalmology (400), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. FAU - Hoyng, Carel B AU - Hoyng CB AD - Department of Ophthalmology (400), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Carel.Hoyng@Radboudumc.nl. LA - eng GR - ./Stichting A.F. Deutman Oogheelkunde Researchfonds/ GR - ./Nederlandse Oogonderzoek Stichting/ GR - ./UitZicht/ PT - Journal Article DEP - 20190322 PL - Germany TA - Graefes Arch Clin Exp Ophthalmol JT - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JID - 8205248 RN - 0 (ABCA4 protein, human) RN - 0 (ATP-Binding Cassette Transporters) SB - IM MH - ATP-Binding Cassette Transporters/genetics/metabolism MH - Adolescent MH - Adult MH - Child MH - Child, Preschool MH - Diagnostic Errors MH - Electroretinography/*methods MH - Female MH - Fluorescein Angiography/*methods MH - Fundus Oculi MH - Genetic Testing MH - Humans MH - Infant MH - Macular Degeneration/*congenital/diagnosis/genetics/metabolism MH - Male MH - Ophthalmoscopy MH - Retinal Pigment Epithelium/*pathology MH - Stargardt Disease MH - Tomography, Optical Coherence/*methods MH - *Visual Acuity MH - Young Adult OTO - NOTNLM OT - Childhood-onset STGD1 OT - Fundus abnormalities OT - Retinal dystrophy OT - Stargardt disease EDAT- 2019/03/25 06:00 MHDA- 2019/06/06 06:00 CRDT- 2019/03/24 06:00 PHST- 2018/08/20 00:00 [received] PHST- 2019/02/18 00:00 [accepted] PHST- 2018/12/09 00:00 [revised] PHST- 2019/03/25 06:00 [pubmed] PHST- 2019/06/06 06:00 [medline] PHST- 2019/03/24 06:00 [entrez] AID - 10.1007/s00417-019-04280-8 [pii] AID - 10.1007/s00417-019-04280-8 [doi] PST - ppublish SO - Graefes Arch Clin Exp Ophthalmol. 2019 Jun;257(6):1147-1157. doi: 10.1007/s00417-019-04280-8. Epub 2019 Mar 22.