RESUMO
BACKGROUND: KCNV2-associated retinopathy is an autosomal recessive inherited retinal disease classically named cone dystrophy with supernormal rod response (CDSRR). This study aims to identify the best biomarker for evaluating the condition. METHODS: A retrospective review of eight patients from seven families with genetically confirmed KCNV2-associated retinopathy was performed. The best corrected visual acuity (BCVA), full-field electroretinogram (ffERG), pattern ERG (pERG), fundus imaging: retinal photograph and fundus autofluorescence (FAF), and optical coherence tomography (OCT) were analysed. RESULTS: There was a disproportionate increase in b-wave amplitude with a relatively small light intensity increase, especially between the two dimmest stimuli of DA 0.002 and 0.01 (-2.7 and -2.0 log cd.s/m2). The a-wave amplitude was normal. The a-wave peak time was delayed in all stimuli. The b-wave peak time was delayed compared to normal, but the gap tightened as intensity increased. The b:a wave ratio was above or at the upper limit for the reference values. FAF bull's eye maculopathy pattern was prominent and variable foveal disruption on OCT was apparent in all patients. Legal blindness was reached before the age of 25. CONCLUSIONS: We identified three potential electrophysiology biomarkers to assist in evaluating future therapies: the disproportionate b-wave amplitude jump, delayed a-wave and b-wave peak time, and the higher than normal b:a wave ratio. Any of these biomarkers found with photoreceptor ellipsoid zone foveal-perifoveal disruption should prompt consideration for KCNV2 retinopathy. The BCVA natural history data suggests the probable optimum therapeutic window in the first three decades of life.
Assuntos
Biomarcadores , Eletrorretinografia , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Masculino , Feminino , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Adulto , Acuidade Visual/fisiologia , Biomarcadores/metabolismo , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Criança , Angiofluoresceinografia/métodos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Distrofia de Cones/genética , Distrofia de Cones/diagnóstico , Distrofia de Cones/fisiopatologia , MutaçãoRESUMO
BACKGROUND: Neuronal ceroid lipofuscinosis is a group of neurodegenerative disorders with varying visual dysfunction. CLN3 is a subtype which commonly presents with visual decline. Visual symptomatology can be indistinct making early diagnosis difficult. This study reports ocular biomarkers of CLN3 patients to assist clinicians in early diagnosis, disease monitoring, and future therapy. METHODS: Retrospective review of 5 confirmed CLN3 patients in our eye clinic. Best corrected visual acuity (BCVA), electroretinogram (ERG), ultra-widefield (UWF) fundus photography and fundus autofluorescence (FAF), and optical coherence tomography (OCT) studies were undertaken. RESULTS: Five unrelated children, 4 females and 1 male, with median age of 6.2 years (4.6-11.7) at first assessment were investigated at the clinic from 2016 to 2021. Four homozygous and one heterozygous pathogenic CLN3 variants were found. Best corrected visual acuities (BCVAs) ranged from 0.18 to 0.88 logMAR at first presentation. Electronegative ERGs were identified in all patients. Bull's eye maculopathies found in all patients. Hyper-autofluorescence ring surrounding hypo-autofluorescence fovea on FAF was found. Foveal ellipsoid zone (EZ) disruptions were found in all patients with additional inner and outer retinal microcystic changes in one patient. Neurological problems noted included autism, anxiety, motor dyspraxia, behavioural issue, and psychomotor regression. CONCLUSIONS: CLN3 patients presented at median age 6.2 years with visual decline. Early onset maculopathy with an electronegative ERG and variable cognitive and motor decline should prompt further investigations including neuropaediatric evaluation and genetic assessment for CLN3 disease. The structural parameters such as EZ and FAF will facilitate ocular monitoring.
Assuntos
Eletrorretinografia , Doenças Retinianas , Criança , Feminino , Humanos , Masculino , Retina , Imagem Multimodal , Eletrofisiologia , Tomografia de Coerência Óptica/métodos , Glicoproteínas de Membrana/genética , Chaperonas Moleculares/genéticaRESUMO
BACKGROUND: The electronegative electroretinogram (ERG) reflecting inner retinal dysfunction can assist as a diagnostic tool to determine the anatomical location in eye disease. The aim of this study is to determine the frequency and aetiology of electronegative ERG in a tertiary ophthalmology centre and to develop a clinical algorithm to assist patient management. METHODS: Retrospective review of ERGs performed at the Save Sight Institute from January 2011 to December 2020. ERGs were performed according to ISCEV standard. The b:a ratio was analysed in dark adapted (DA) 3.0 or 12.0 recordings. Patients with ratio of ≤1.0 were included. RESULTS: A total of 4421 patients had ERGs performed during study period, of which 139 patients (3.1%) had electronegative ERG. The electronegative ERG patients' median age at referral time was 37 (0.7-90.6) years. The causative aetiologies were photoreceptor dystrophy (48, 34.5%), Congenital Stationary Night Blindness (CSNB) (33, 23.7%), retinal ischemia (18, 12.9%), retinoschisis (15, 10.8%), paraneoplastic autoimmune retinopathy (PAIR) and nonPAIR (14, 10.1%), batten disease (4, 2.9%), and inflammatory retinopathy (4, 2.9%). There were three patients with an unclassified diagnosis. Thirty-two patients (23%) had good vision and a normal fundus appearance. Eleven patients (7.9%) had good vision and normal results in all multimodal imaging. CONCLUSIONS: The frequency of electronegative ERG in our referral centre was 3.1% with photoreceptor dystrophy as the main aetiology. A significant number of the cases had good vision with normal fundus or normal multimodal imaging. This further highlights the value of an ERG in this modern multimodal imaging era.
Assuntos
Doenças Autoimunes , Cegueira Noturna , Doenças Retinianas , Eletrorretinografia/métodos , Humanos , Imagem Multimodal , Cegueira Noturna/diagnóstico , Doenças Retinianas/diagnósticoRESUMO
BACKGROUND: Inosine monophosphate dehydrogenase (IMPDH) is a key regulatory enzyme in the de novo synthesis of the purine base guanine. Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) are causative for RP10 autosomal dominant retinitis pigmentosa (adRP). This study reports a novel variant in a family with IMPDH1-associated retinopathy. We also performed a comprehensive review of all reported IMPDH1 disease causing variants with their associated phenotype. MATERIALS AND METHODS: Multimodal imaging and functional studies documented the phenotype including best-corrected visual acuity (BCVA), fundus photograph, fundus autofluorescence (FAF), full field electroretinogram (ffERG), optical coherence tomography (OCT) and visual field (VF) data were collected. A literature search was performed in the PubMed and LOVD repositories. RESULTS: We report 3 cases from a 2-generation family with a novel heterozygous likely pathogenic variant p. (Lys314Gln) (exon 10). The ophthalmic phenotype showed diffuse outer retinal atrophy with mild pigmentary changes with sparse pigmentary changes. FAF showed early macular involvement with macular hyperautofluorescence (hyperAF) surrounded by hypoAF. Foveal ellipsoid zone island can be found in the youngest patient but not in the older ones. The literature review identified a further 56 heterozygous, 1 compound heterozygous, and 2 homozygous variant. The heterozygous group included 43 missense, 3 in-frame, 1 nonsense, 2 frameshift, 1 synonymous, and 6 intronic variants. Exon 10 was noted as a hotspot harboring 18 variants. CONCLUSIONS: We report a novel IMPDH1 variant. IMPDH1-associated retinopathy presents most frequently in the first decade of life with early macular involvement.
Assuntos
Degeneração Retiniana , Retinose Pigmentar , Humanos , Inosina Monofosfato , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Mutação , Oxirredutases/genética , Tomografia de Coerência Óptica , Eletrorretinografia , Linhagem , IMP Desidrogenase/genéticaRESUMO
PURPOSE: Mer tyrosine kinase-retinitis pigmentosa (MERTK-RP) causes a primary defect in the retinal pigment epithelium, which subsequently affects rod and cone photoreceptors. The study aims to identify the most appropriate MERTK-RP biomarkers to measure disease progression for deciding the optimum therapeutic trial intervention time. MATERIALS AND METHODS: Patients' data from baseline (BL) and last follow-up (LFU) were reviewed. Best corrected visual acuity (BCVA), spectral domain-optical coherence tomography (SD-OCT), ultra-widefield fundus autofluorescence (UWF-FAF) patterns, kinetic perimetry (KP), and electroretinography (ERG) parameters were analyzed. RESULTS: Five patients were included with the mean age of 17.7 ± 14.4 years old (6.7-42.3) at BL and mean BCVA follow-up of 8.4 ± 5.1 years. Mean BCVA at BL and LFU were 0.84 ± 0.86 LogMAR and 1.14 ± 0.86 LogMAR, respectively. The BCVA decline rate was 0.05 ± 0.03 LogMAR units/year. Ellipzoid zones (EZ) were measurable in eight eyes with mean BL length of 1293.75 ± 421.07 µm and reduction of 140.95 ± 69.28 µm/year and mean BL CMT of 174.2 ± 37.52 µm with the rate of 11.2 ± 12.77 µm declining/year. Full-field ERG (ffERG) and pattern ERG (pERG) were barely recordable. UWF-FAF showed central macular hyper-autofluorescence (hyperAF). KP (III4e and V4e) was normal in two eyes, restricted nasally in four eyes, superior wedge defect in two eyes and undetectable in two eyes. The four restricted nasally KPs became worse, while the others stayed almost unchanged. CONCLUSIONS: This cohort showed early visual loss, moderately rapid EZ reduction and macular hyperAF. EZ, CMT, and BCVA were consistently reduced. Relative rapid decline in these biomarkers reflecting visual function suggests an early and narrow timespan for intervention.