We aim to report the ocular phenotype and molecular genetic findings in two Czech families with Sorsby fundus dystrophy and to review all the reported TIMP3 pathogenic variants. Two probands with Sorsby fundus dystrophy and three first-degree relatives underwent ocular examination and retinal imaging, including optical coherence tomography angiography. The DNA of the first proband was screened using a targeted ocular gene panel, while, in the second proband, direct sequencing of the TIMP3 coding region was performed. Sanger sequencing was also used for segregation analysis within the families. All the previously reported TIMP3 variants were reviewed using the American College of Medical Genetics and the Association for Molecular Pathology interpretation framework. A novel heterozygous variant, c.455A>G p.(Tyr152Cys), in TIMP3 was identified in both families and potentially de novo in one. Optical coherence tomography angiography documented in one patient the development of a choroidal neovascular membrane at 54 years. Including this study, 23 heterozygous variants in TIMP3 have been reported as disease-causing. Application of gene-specific criteria denoted eleven variants as pathogenic, eleven as likely pathogenic, and one as a variant of unknown significance. Our study expands the spectrum of TIMP3 pathogenic variants and highlights the importance of optical coherence tomography angiography for early detection of choroidal neovascular membranes.

• MeSH
• lidé MeSH
• makulární degenerace * MeSH
• mutace MeSH
• neovaskularizace choroidey * MeSH
• oči MeSH
• tkáňový inhibitor metaloproteinasy 3 genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

PURPOSE: Danon disease (DD) is a rare X-linked disorder caused by pathogenic variants in LAMP2. DD primarily manifests as a severe cardiomyopathy. An early diagnosis is crucial for patient survival. The aim of the study was to determine the usefulness of ocular examination for identification of DD. METHODS: Detailed ocular examination in 10 patients with DD (3 males, 7 females) and a 45-year-old asymptomatic female somatic mosaic carrier of a LAMP2 disease-causing variant. RESULTS: All patients with manifest cardiomyopathy had pigmentary retinopathy with altered autofluorescence and diffuse visual field loss. Best corrected visual acuity (BCVA) was decreased (<0.63) in 8 (40%) out of 20 eyes. The severity of retinal pathology increased with age, resulting in marked cone-rod involvement overtime. Spectral-domain optical coherence tomography in younger patients revealed focal loss of photoreceptors, disruption and deposition at the retinal pigment epithelium/Bruch's membrane layer (corresponding to areas of marked increased autofluorescence), and hyperreflective foci in the outer nuclear layer. Cystoid macular oedema was seen in one eye. In the asymptomatic female with somatic mosaicism, the BCVA was 1.0 bilaterally. An abnormal autofluorescence pattern in the left eye was present; while full-field electroretinography was normal. CONCLUSIONS: Detailed ocular examination may represent a sensitive and quick screening tool for the identification of carriers of LAMP2 pathogenic variants, even in somatic mosaicism. Hence, further investigation should be undertaken in all patients with pigmentary retinal dystrophy as it may be a sign of a life-threatening disease.

• MeSH
• dospělí MeSH
• elektroretinografie MeSH
• glykogenóza typu IIb komplikace   diagnóza   genetika   MeSH
• lidé MeSH
• membránový protein 2 asociovaný s lyzozomy biosyntéza   genetika   MeSH
• mladý dospělý MeSH
• optická koherentní tomografie metody   MeSH
• regulace genové exprese * MeSH
• retinální pigmentový epitel patologie   MeSH
• retinopathia pigmentosa diagnóza   etiologie   genetika   MeSH
• RNA genetika   MeSH
• rodokmen MeSH
• zraková ostrost * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dospělí MeSH
• Fabryho nemoc * MeSH
• fundus oculi MeSH
• katarakta MeSH
• lidé MeSH
• oční symptomy * MeSH
• retina patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Cíle: Premakulární krvácení a krvácení pod vnitřní limitující membránu (ILM) sítnice patří mezi příčiny náhlého zhoršení centrální zrakové ostrosti. Retrospektivně byly hodnoceny anatomické a funkční výsledky různých terapeutických možností. Materiál a metody: Soubor tvořily tři oči tří pacientů (2 ženy a 1 muž). Pomocí vyšetření optickou koherenční tomografií se spektrální doménou byla upřesněna u obou žen subhyaloidní lokalizace premakulárního krvácení a u muže krvácení pod ILM sítnice. Vstupní centrální zraková ostrost (CZO) byla u obou žen 0,63, u muže 0,16. U pacientky s juxtafoveolárním krvácením při antikoagulační terapii warfarinem byl zvolen konzervativní postup, pacientka s krvácením v souvislosti s proliferativní diabetickou retinopatií (PDR) podstoupila Nd:YAG laserovou hyaloidotomii zadní sklivcové membrány. U muže s neobjasněnou příčinou krvácení byla provedena 25-Gauge pars plana vitrektomie s peelingem ILM a následné ultrastrukturální morfometrické a histopatologické vyšetření ILM. Výsledky: U všech pacientů bylo dosaženo zlepšení jak CZO, tak nálezu na sítnici. Výsledná CZO byla u pacientky s PDR 0,8, u ostatních pacientů 1,0. Po dobu sledování nebyly zaznamenány žádné komplikace. Histopatologické a morfometrické vyšetření prokázalo variabilní tloušťku ILM (2,70 ±1,58 μm) a fibroblasty a makrofágy s depozity hemosiderinu na retinální straně ILM. Závěr: Volba léčebného postupu u premakulárního krvácení či krvácení pod ILM závisí na vstupních parametrech, jakými jsou CZO, rozsah a lokalizace krvácení, a také celkový zdravotní stav pacienta. Nd:YAG laserová hyaloidotomie zadní sklivcové membrány je efektivní metoda pro rychlou obnovu zrakových funkcí. Chirurgické sloupnutí ILM a následné odsátí krvácení vede k odstranění rozpadových produktů hemoglobinu a k minimalizaci rizika vzniku sekundárních membrán na povrchu sítnice.

Introduction: Premacular hemorrhage (PH) and sub-internal limiting membrane hemorrhage (sub-ILM-H) are among the causes of sudden deterioration of central visual acuity. Anatomical and functional outcomes of different therapeutic options were evaluated retrospectively. Methods: The study included three eyes of three patients (2 females and 1 male). Location of the hemorrhage was determined by spectral domain optical coherence tomography. Subhyaloid premacular location of the hemorrhage was proven in one eye of each woman and sub-ILM location of the hemorrhage in one eye of the male. The baseline best corrected visual acuity (BCVA) was 0.63 in the eyes of the females and 0.16 in the eye of the male. Conservative treatment option was chosen in case of juxtafoveolar PH in the eye of the female patient on anticoagulant warfarin therapy. The female patient with PH secondary to proliferative diabetic retinopathy (PDR) underwent Nd: YAG laser hyaloidotomy. The male patient with unexplained cause of the sub- ILM-H underwent 25-Gauge vitrectomy with ILM peeling and subsequent ultrastructural morphometric and histopathological examination of the ILM. Results: Both BCVA and retinal finding improvement were achieved in all patients. Final BCVA was 0.8 in the eye of the female patient with PDR and 1.0 in rest of the eyes of the other patients. No complications were recorded at follow-up visits. Histopathological and morphometric examination demonstrated variable ILM thickness (2.70 ±1.58 μm) and proved presence of fibroblasts and macrophages with hemosiderin deposits on the retinal side of ILM. Conclusion: The choice of the treatment option of PH and sub-ILM-H depends on input parameters such as the initial BCVA, the extent and the location of the hemorrhage, as well as the overall health of the patient. Nd: YAG laser hyaloidotomy is an effective method for rapid recovery of visual functions. Surgical ILM peeling and aspiration of the underlying hemorrhage result in the removal of breakdown products of hemoglobin and minimization of the risk of secondary epiretinal membranes development.

• MeSH
• bazální membrána MeSH
• epiretinální membrána chirurgie   MeSH
• lidé MeSH
• optická koherentní tomografie MeSH
• retinální krvácení * chirurgie   diagnóza   etiologie   MeSH
• retrospektivní studie MeSH
• vitrektomie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

CONTEXT: Methanol poisoning induces acute optic neuropathy with possible long-term visual damage. OBJECTIVE: To study the dynamics and key determinants of visual pathway functional changes during 4 years after acute methanol poisoning. METHODS: A total of 42 patients with confirmed methanol poisoning (mean age 45.7 ± 4.4 years) were examined 4.9 ± 0.6, 25.0 ± 0.6, and 49.9 ± 0.5 months after discharge. The following tests were performed: visual evoked potential (VEP), retinal nerve fiber layer (RNFL) measurement, brain magnetic resonance imaging (MRI), complete ocular examination, biochemical tests, and apolipoprotein E (ApoE) genotyping. RESULTS: Abnormal VEP P1 latency was registered in 18/42 right eyes (OD) and 21/42 left eyes (OS), abnormal N1P1 amplitude in 10/42 OD and OS. Mean P1 latency shortening during the follow-up was 15.0 ± 2.0 ms for 36/42 (86%) OD and 14.9 ± 2.4 ms for 35/42 (83%) OS, with maximum shortening up to 35.0 ms. No significant change of mean N1P1 amplitude was registered during follow-up. A further decrease in N1P1 amplitude ≥1.0 mcV in at least one eye was observed in 17 of 36 patients (47%) with measurable amplitude (mean decrease -1.11 ± 0.83 (OD)/-2.37 ± 0.66 (OS) mcV versus -0.06 ± 0.56 (OD)/-0.83 ± 0.64 (OS) mcV in the study population; both p < .001). ApoE4 allele carriers had lower global and temporal RNFL thickness and longer initial P1 latency compared to the non-carriers (all p < .05). The odds ratio for abnormal visual function was 8.92 (3.00-36.50; 95%CI) for ApoE4 allele carriers (p < .001). The presence of ApoE4 allele was further associated with brain necrotic lesions (r = 0.384; p = .013) and brain hemorrhages (r = 0.395; p = .011). CONCLUSIONS: Improvement of optic nerve conductivity occurred in more than 80% of patients, but evoked potential amplitude tended to decrease during the 4 years of observation. ApoE4 allele carriers demonstrated lower RNFL thickness, longer P1 latency, and more frequent methanol-induced brain damage compared to non-carriers.

• MeSH
• apolipoprotein E4 genetika   MeSH
• časové faktory MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• methanol otrava   MeSH
• následné studie MeSH
• nemoci zrakového nervu chemicky indukované   diagnóza   genetika   patofyziologie   MeSH
• nervus opticus účinky léků   patofyziologie   MeSH
• poruchy zraku chemicky indukované   diagnóza   genetika   patofyziologie   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• reakční čas MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• zrak účinky léků   genetika   MeSH
• zrakové evokované potenciály MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

PURPOSE: In this prospective observational comparative case series, we aimed to study the peripapillary capillary network with spectral-domain optical coherence tomography angiography (OCT-A) in Leber hereditary optic neuropathy (LHON). METHODS: Twelve eyes of six individuals, of these three males (five eyes) after clinical onset of visual impairment were imaged by OCT-A with scans centred on optic discs. Control group consisted of 6 eyes with no visual impairment. RESULTS: The three affected individuals lost vision 6 years (at age 22 years), 2 years and 3 months (at age 26 years) and 1 year and 2 months (at age 30 years) prior to OCT-A examination. All five affected eyes had alterations in density of the radial peripapillary microvascular network at the level of retinal nerve fibre layer, including an eye of a patient treated with idebenone that underwent almost full recovery (best corrected visual acuity 0.87). Interestingly, the other eye showed normal ocular findings 14 months after onset. Results of OCT-A examination in this eye were unfortunately inconclusive due to a delineation error. At the level of the ganglion cell layer differences could be also noted, but only in two severely affected individuals. There were no differences between unaffected mutation carriers and control eyes. CONCLUSION: Optical coherence tomography angiography scans confirmed that the peripapillary microvascular network is highly abnormal in eyes manifesting visual impairment due to LHON. These findings support the hypothesis that microangiopathy contributes to the development of vision loss in this mitochondrial disorder.

• MeSH
• discus nervi optici krevní zásobení   diagnostické zobrazování   MeSH
• dítě MeSH
• dospělí MeSH
• fluoresceinová angiografie metody   MeSH
• fundus oculi MeSH
• Leberova atrofie zrakového nervu diagnóza   patofyziologie   MeSH
• lidé MeSH
• mikrocévy diagnostické zobrazování   MeSH
• mikrocirkulace fyziologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nervová vlákna patologie   MeSH
• optická koherentní tomografie metody   MeSH
• prospektivní studie MeSH
• retinální cévy diagnostické zobrazování   patofyziologie   MeSH
• retinální gangliové buňky patologie   MeSH
• zraková ostrost * MeSH
• zraková pole MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH

Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a severe metabolic disease manifesting as muscle hypotonia, developmental delay, cerebellar ataxia and ocular symptoms; typically, nystagmus and optic disc pallor. Recently, early onset retinal dystrophy has been reported as an additional feature. In this study, we summarize ocular phenotypes and SRD5A3 variants reported to be associated with SRD5A3-CDG. We also describe in detail the ophthalmic findings in a 12-year-old Czech child harbouring a novel homozygous variant, c.436G>A, p.(Glu146Lys) in SRD5A3. The patient was reviewed for congenital nystagmus and bilateral optic neuropathy diagnosed at 13 months of age. Examination by spectral domain optical coherence tomography and fundus autofluorescence imaging showed clear signs of retinal dystrophy not recognized until our investigation. Best corrected visual acuity was decreased to 0.15 and 0.16 in the right and left eye, respectively, with a myopic refractive error of -3.0 dioptre sphere (DS) / -2.5 dioptre cylinder (DC) in the right and -3.0 DS / -3.0 DC in the left eye. The proband also had optic head nerve drusen, which have not been previously observed in this syndrome.

• MeSH
• 3-oxo-5-alfa-steroid-4-dehydrogenasa chemie   genetika   MeSH
• dítě MeSH
• fenotyp MeSH
• homozygot MeSH
• lidé MeSH
• membránové proteiny chemie   genetika   MeSH
• mutace genetika   MeSH
• oči patologie   MeSH
• rodokmen MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• vrozené poruchy glykosylace enzymologie   genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

PURPOSE: To describe the ocular findings of 12 subjects with paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance (MGUS). METHODS: Ocular examination included corneal spectral domain optical coherence tomography. In three individuals with an initial diagnosis of a lattice or Thiel-Behnke corneal dystrophy, the TGFBI gene was screened by conventional Sanger sequencing. RESULTS: We confirmed a diagnosis of MGUS by systemic examination and serum protein electrophoresis in 12 individuals (9 males and 3 females), with a mean age at presentation of 52.2 years (range 24-63 years) and mean follow-up 6.4 years (range 0-17 years). The best-corrected visual acuity (BCVA) at presentation ranged from 1.25 to 0.32. In all individuals, the corneal opacities were bilateral. The appearances were diverse and included superficial reticular opacities and nummular lesions, diffuse posterior stromal opacity, stromal lattice lines, superficial and stromal crystalline deposits, superficial haze and a superficial ring of hypertrophic tissue. In one individual, with opacities first recorded at 24 years of age, we documented the progression of corneal disease over the subsequent 17 years. In another individual, despite systemic treatment for MGUS, recurrence of deposits was noted following bilateral penetrating keratoplasties. The three individuals initially diagnosed with inherited corneal dystrophy were negative for TGFBI mutations by direct sequencing. CONCLUSION: A diagnosis of MGUS should be considered in patients with bilateral corneal opacities. The appearance can mimic corneal dystrophies or cystinosis. In our experience, systemic treatment of MGUS did not prevent recurrence of paraproteinemic keratopathy following keratoplasty.

• MeSH
• dospělí MeSH
• keratoplastika perforující škodlivé účinky   MeSH
• konfokální mikroskopie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• monoklonální gamapatie nejasného významu komplikace   MeSH
• následné studie MeSH
• optická koherentní tomografie MeSH
• paraproteinemie komplikace   diagnóza   MeSH
• předpověď * MeSH
• recidiva MeSH
• rohovka patologie   MeSH
• senioři MeSH
• vyšetření štěrbinovou lampou MeSH
• zákal rohovky diagnóza   etiologie   MeSH
• zraková ostrost MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• Fabryho nemoc * diagnostické zobrazování   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci rohovky diagnostické zobrazování   MeSH
• oční symptomy MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• lidé MeSH
• methanol MeSH
• nemoci zrakového nervu * MeSH
• prospektivní studie MeSH
• zánět zrakového nervu * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH