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Purpose: To describe a novel case of Norrie disease and X-linked Kabuki syndrome caused by a microdeletion encompassing multiple genes on the X chromosome. Observations: A 3-day-old boy born at full term had bilateral retrolental fibrovascular plaques. Surgery with lensectomy and vitrectomy revealed bilateral, closed funnel retinal detachments consistent with a clinical diagnosis of Norrie disease. In addition, the baby had congenital heart defects, hearing loss, and dysmorphic facies. His mother carried a clinical diagnosis of Kabuki syndrome. Genetic testing of the baby revealed an Xp11.3 microdeletion that included the NDP and KDM6A genes, confirming the baby had both Norrie disease and X-linked Kabuki syndrome. The mother was found via ultrawide-field fluorescein angiography to have asymptomatic peripheral retinal vascular anomalies, consistent with NDP-associated familial exudative vitreoretinopathy (FEVR). Conclusions and importance: This is the first reported case of Norrie disease together with X-linked Kabuki syndrome. Contiguous gene deletions may explain some of the variable systemic involvement in Norrie disease.
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OBJECTIVE: Choroidal neovascularization (CNV) is usually considered to be a late-stage complication in Best vitelliform macular dystrophy (BVMD) and can be difficult to diagnose with fluorescein angiography. This study used swept-source (SS) OCT angiography (OCTA) to evaluate the prevalence of CNV in BVMD, identify structural features associated with CNV, and provide insight into the role of CNV in vitelliform lesion evolution. DESIGN: Institutional review board-approved, retrospective, cross-sectional, and longitudinal study. PARTICIPANTS: Patients with molecularly confirmed BVMD. METHODS: Charts from consecutive patients with BVMD imaged with SS-OCTA (PLEX Elite 9000, Carl-Zeiss Meditec Inc) at the University of Iowa from September 2017 to October 2021 were reviewed. Clinical data, including age, gender, best-corrected visual acuity (BCVA), and treatment with intravitreal anti-VEGF injections were recorded. The presence of CNV on SS-OCTA was determined by expert graders and correlated with structural features, such as interstitial fluid, subretinal fluid, nodular subretinal pillar, focal choroidal excavation (FCE), and subfoveal choroidal thickness, with a P value of < 0.05 considered statistically significant. MAIN OUTCOME MEASURES: Presence of CNV on SS-OCTA and correlation with structural features on SS-OCT. RESULTS: A total of 53 eyes from 27 patients (13 women; 48.1%) were included. The mean age was 45 years (range, 8-79 years), and the mean logarithm of the minimum angle of resolution BCVA was 0.38 (range, 0-1). Choroidal neovascularization was identified on SS-OCTA in 27 eyes (50.9%), of which 63.0% had a vitelliform (Gass stage 2) lesion. In 40.7% (11 of 27) of eyes, there was no prior clinical diagnosis of CNV. Other structural features associated with CNV included FCEs (15.1%, 8 of 53 eyes) and nodular pillars (15.1%, 8 of 53 eyes) (P < 0.01). Seven patients had available longitudinal imaging, and most of these patients had CNV visible on SS-OCTA (71.4%; 10 of 14 eyes). CONCLUSION: Choroidal neovascularization is common in BVMD, including in the early stages of the disease. The presence of FCEs or nodular pillars should heighten the clinical suspicion of CNV, which may accelerate vitelliform lesion evolution. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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Neovascularização de Coroide , Distrofia Macular Viteliforme , Humanos , Feminino , Pessoa de Meia-Idade , Distrofia Macular Viteliforme/complicações , Distrofia Macular Viteliforme/diagnóstico , Distrofia Macular Viteliforme/patologia , Estudos Retrospectivos , Estudos Longitudinais , Estudos Transversais , Tomografia de Coerência Óptica/métodos , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologiaRESUMO
AIMS: Automated machine learning (AutoML) is a novel tool in artificial intelligence (AI). This study assessed the discriminative performance of AutoML in differentiating retinal vein occlusion (RVO), retinitis pigmentosa (RP) and retinal detachment (RD) from normal fundi using ultra-widefield (UWF) pseudocolour fundus images. METHODS: Two ophthalmologists without coding experience carried out AutoML model design using a publicly available image data set (2137 labelled images). The data set was reviewed for low-quality and mislabeled images and then uploaded to the Google Cloud AutoML Vision platform for training and testing. We designed multiple binary models to differentiate RVO, RP and RD from normal fundi and compared them to bespoke models obtained from the literature. We then devised a multiclass model to detect RVO, RP and RD. Saliency maps were generated to assess the interpretability of the model. RESULTS: The AutoML models demonstrated high diagnostic properties in the binary classification tasks that were generally comparable to bespoke deep-learning models (area under the precision-recall curve (AUPRC) 0.921-1, sensitivity 84.91%-89.77%, specificity 78.72%-100%). The multiclass AutoML model had an AUPRC of 0.876, a sensitivity of 77.93% and a positive predictive value of 82.59%. The per-label sensitivity and specificity, respectively, were normal fundi (91.49%, 86.75%), RVO (83.02%, 92.50%), RP (72.00%, 100%) and RD (79.55%,96.80%). CONCLUSION: AutoML models created by ophthalmologists without coding experience can detect RVO, RP and RD in UWF images with very good diagnostic accuracy. The performance was comparable to bespoke deep-learning models derived by AI experts for RVO and RP but not for RD.
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Inteligência Artificial , Oclusão da Veia Retiniana , Humanos , Curva ROC , Fundo de Olho , Aprendizado de Máquina , RetinaRESUMO
BACKGROUND: X-linked retinitis pigmentosa (XLRP) is the most severe form of retinitis pigmentosa (RP) and accounts for 15-20% of all RP cases. In this study, we investigated the progression of visual acuity loss across age groups in female carriers and compared it to affected males. METHODS: A PubMed literature search was conducted, and RP2 cases were included based on specific inclusion criteria. Visual acuity (VA), refractive error spherical equivalent (SE), and retinal findings were recorded. Cross-sectional analyses investigated the relationship between VA and age in carrier females and affected males. Genotype-phenotype VA correlations were studied using t-tests. RESULTS: 35 carrier females and 28 affected males with confirmed RP2 mutations were collected from 13 studies. The mean age and logMAR VA of carrier females were 44.2 ± 17.4 years, and 0.5 ± 0.5, respectively. 78.8% of carrier females showed abnormal XLRP-related fundus findings and had significantly reduced VA compared to those with normal fundi (0.6 ± 0.5 vs. 0.1 ± 0.1; p = 0.03). Compared to affected males, no statistical correlation was found between logMAR VA and advancing age in carrier females (p = 0.75). Statistically significant linear correlations were found between logMAR VA and SE in each of carrier females (p = 0.01). There were no observed differences in logMAR VA based on mutation type (p = 0.97) or mutation location (p = 0.83). Anisometropia was observed in 38% of carrier females and 68% of affected males; these prevalence numbers are statistically significant between the two groups (1.7 ± 0.3 vs. 3.9 ± 10.9 dioptres; p = 0.03). CONCLUSIONS: RP2 carrier females generally maintain good VA throughout their lifetime, as opposed to affected males, whose vision progressively declines. Our study provides important VA prognostic data that is crucial for patient counseling.
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Proteínas de Ligação ao GTP , Retinose Pigmentar , Masculino , Feminino , Humanos , Estudos Transversais , Proteínas de Ligação ao GTP/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Olho/genética , Proteínas de Membrana/genética , Campos Visuais , Eletrorretinografia , Genótipo , Acuidade Visual , Mutação , Retinose Pigmentar/genéticaRESUMO
The overlapping genetic and clinical spectrum in inherited retinal degeneration (IRD) creates challenges for accurate diagnoses. The goal of this work was to determine the genetic diagnosis and clinical features for patients diagnosed with an IRD. After signing informed consent, peripheral blood or saliva was collected from 64 patients diagnosed with an IRD. Genetic testing was performed on each patient in a Clinical Laboratory Improvement Amendments of 1988 (CLIA) certified laboratory. Mutations were verified with Sanger sequencing and segregation analysis when possible. Visual acuity was measured with a traditional Snellen chart and converted to a logarithm of minimal angle of resolution (logMAR). Fundus images of dilated eyes were acquired with the Optos® camera (Dunfermline, UK). Horizontal line scans were obtained with spectral-domain optical coherence tomography (SDOCT; Spectralis, Heidelberg, Germany). Genetic testing combined with segregation analysis resolved molecular and clinical diagnoses for 75% of patients. Ten novel mutations were found and unique genotype phenotype associations were made for the genes RP2 and CEP83. Collective knowledge is thereby expanded of the genetic basis and phenotypic correlation in IRD.
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Retina , Degeneração Retiniana , Humanos , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/genética , Testes Genéticos , Mutação , Estudos de Associação GenéticaRESUMO
PURPOSE: The overall goal was to restore a normal and synchronous blink in unilateral lagophthalmos. We describe the biocompatibility profiling of a novel ferromagnetic implant used for electromagnetic eyelid force generation. METHODS: A non-contact blink detection system and an electromagnetic stimulation system were designed and tested. A modified Lester-Burch speculum equipped with strain gauge technology was used in blinking force measurement. Samarium-cobalt magnets were prototyped and coated with parylene-C. Biocompatibility testing was performed using NIH/3T3 mouse fibroblast cells with MTT colorimetric assay cytotoxic quantification. OUTCOME MEASURES: Cellular viability and interleukin concentrations. RESULTS: Our system was capable of detecting 95.5 ± 3.6% of blinks in various lighting conditions. Using our force measuring device, the difference between non-paralyzed and paralyzed orbicularis oculi (OO) for normal and forceful blinking closure was 40.4 g and 101.9 g, respectively. A 16.6 × 5.0 × 1.5 mm curved shaped samarium cobalt eyelid implant was successfully developed and showed a reproducible blink at 100 ms with full corneal coverage with external eyelid taping. Compared to gold weights, parylene-C coated samarium cobalt implants showed not only excellent cell viability (82.0 ± 4.9% vs. 88.4 ± 0.9%, respectively, p > .05), but also below detection threshold for pro-inflammatory marker concentrations (interleukin-6 < 2 pg/mL and interleukin-10 < 3 pg/mL). CONCLUSIONS: We demonstrated excellent in-vitro biocompatibility of our parylene-C coated samarium cobalt implants. We believe that our novel approach can improve the quality-of-life of affected individuals and provides new understanding of blinking biomechanics.
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Piscadela , Doenças Palpebrais , Animais , Pálpebras , Humanos , Fenômenos Magnéticos , Camundongos , Próteses e ImplantesRESUMO
PURPOSE: The mitochondrial DNA A3243G (m.3243A>G) variant causes a wide spectrum of phenotypes, with pigmentary retinopathy as the most common ocular finding. We undertook this meta-analysis to investigate the clinical course of visual acuity (VA) in patients with m.3243A>G variant and provide key clinical correlations with systemic manifestations. METHODS: A PubMed literature search was performed and studies were selected after satisfying pre-set inclusion criteria. Demographic and clinical data, including retinal findings and systemic manifestations were recorded. Cross-sectional and linear regression analyses were used to investigate the relationship between VA and age, as well as between the age at diagnosis of retinopathy and the mean ages at diagnosis of sensorineural hearing loss or diabetes. The age and prevalence of systemic manifestations among patients with and without retinopathy were studied using t-tests and Mann-Whitney U-tests (performed on binarized data). Likelihood ratios were computed. RESULTS: The mean VA (average of both eyes) of 90 patients (72.2% female; 65/90) were collected from 18 studies published between 1990 and 2018. The baseline mean age was 45.2 years (range 17 to 92). The mean logMAR VA was 0.10 (- 0.12 to 1.39). There was a statistically significant linear correlation between the logMAR VA and age (p = .008). The VA of patients less than or equal to 50 years of age was significantly better than that of patients older than 50 years (0.06 vs.0.18 logMAR, p = .002). 67 patients (74.4%) showed a characteristic pigmentary retinopathy with a mean age at diagnosis of 47.9 years (17 to 92) and VA of 0.14 logMAR (- 0.12 to 1.24). Age at diagnosis of retinopathy was linearly correlated with age at diagnosis of hearing loss or diabetes (p < .001). Patients with retinopathy were more likely to have hearing loss (83.6% vs. 56.5%, p = .03) or diabetes (56.7% vs. 17.4%, p = .001) than those without retinopathy. Those with both hearing loss and diabetes had an earlier onset of retinopathy than those without (46.4 vs. 60.4 years, p = .01). Patients without both hearing loss and diabetes were 5.3-fold less likely to develop a retinopathy. CONCLUSIONS: Patients with m.3243A>G variant pigmentary retinopathy maintain highly functional VA until around the fifth decade of life, after which significant visual decline ensues. Patients without hearing loss and diabetes have a lower likelihood of exhibiting a retinopathy, which tends to appear about one decade after hearing loss and diabetes are diagnosed.
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DNA Mitocondrial/genética , Doenças Mitocondriais/genética , Mutação Puntual , Doenças Retinianas/genética , Acuidade Visual/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Análise Mutacional de DNA , Feminino , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/fisiopatologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/fisiopatologia , Epitélio Pigmentado da Retina/patologia , Adulto JovemRESUMO
Cellular function and survival are critically dependent on the proper functionality of the mitochondrion. Neurodegenerative cellular processes including cellular adenosine triphosphate production, intermediary metabolism control, and apoptosis regulation are all mitochondrially mediated. The A to G transition at position 3243 in the mitochondrial MTTL1 gene that encodes for the leucine transfer RNA (m.3243A>G) causes a variety of diseases, including maternally inherited loss of hearing and diabetes syndrome (MIDD), mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS). Ophthalmological findings-including posterior sub-capsular cataract, ptosis, external ophthalmoplegia, and pigmentary retinopathy- have all been associated with the m.3243A>G variant. Pigmentary retinopathy is, however, the most common ocular finding, occurring in 38% to 86% of cases. To date, little is known about the pathogenesis, natural history, and heteroplasmic and phenotypic correlations of m.3243A>G-associated pigmentary retinopathy. We summarize the current understanding of mitochondrial genetics and pathogenesis of some associated diseases. We then review the pathophysiology, histology, clinical features, treatment, and important ocular and systemic phenotypic manifestations of m.3243A>G variant associated retinopathy. Mitochondrial diseases require a multidisciplinary team approach to ensure effective treatment, regular follow-up, and accurate genetic counseling.
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Síndrome MELAS , Doenças Mitocondriais , Doenças Retinianas , DNA Mitocondrial/genética , Humanos , Síndrome MELAS/genética , Síndrome MELAS/patologia , Mitocôndrias/genética , Doenças Mitocondriais/genéticaRESUMO
We aimed to assess the feasibility of machine learning (ML) algorithm design to predict proliferative vitreoretinopathy (PVR) by ophthalmologists without coding experience using automated ML (AutoML). The study was a retrospective cohort study of 506 eyes who underwent pars plana vitrectomy for rhegmatogenous retinal detachment (RRD) by a single surgeon at a tertiary-care hospital between 2012 and 2019. Two ophthalmologists without coding experience used an interactive application in MATLAB to build and evaluate ML algorithms for the prediction of postoperative PVR using clinical data from the electronic health records. The clinical features associated with postoperative PVR were determined by univariate feature selection. The area under the curve (AUC) for predicting postoperative PVR was better for models that included pre-existing PVR as an input. The quadratic support vector machine (SVM) model built using all selected clinical features had an AUC of 0.90, a sensitivity of 63.0%, and a specificity of 97.8%. An optimized Naïve Bayes algorithm that did not include pre-existing PVR as an input feature had an AUC of 0.81, a sensitivity of 54.3%, and a specificity of 92.4%. In conclusion, the development of ML models for the prediction of PVR by ophthalmologists without coding experience is feasible. Input from a data scientist might still be needed to tackle class imbalance-a common challenge in ML classification using real-world clinical data.
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Aprendizado de Máquina , Complicações Pós-Operatórias/etiologia , Descolamento Retiniano/cirurgia , Vitrectomia/efeitos adversos , Vitreorretinopatia Proliferativa/etiologia , Idoso , Algoritmos , Diagnóstico por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oftalmologistas , Estudos Retrospectivos , Fatores de Risco , Vitrectomia/métodosRESUMO
PURPOSE: To investigate the prognostic value of peripheral retinal nonperfusion in patients with diabetic retinopathy using ultra-widefield fluorescein angiography (UWFA). METHODS: A cross-sectional study included 78 treatment-naïve eyes with nonproliferative and proliferative diabetic retinopathy (NPDR and PDR). Eyes were divided into three groups: mild/moderate NPDR (n = 31), severe NPDR (n = 31), and PDR (n = 16). Three nonperfusion variables were calculated reflecting the proportion of nonperfused to visible retina based on initial UWFA: central nonperfusion (CNP) index, peripheral nonperfusion (PNP) index, and PNP ratio. The relationships between these indices and central subfield thickness (CST) and spectacle-corrected visual acuity (SCVA) were evaluated. RESULTS: CNP and PNP indices were significantly higher in the PDR group vs. mild/moderate NPDR group (p = 0.007 and 0.008, respectively) but not in the PDR group vs. severe NPDR group (p = 0.149 and p = 0.535, respectively). A significant linear correlation was found between the CNP and PNP indices in both severe NPDR and PDR groups (R2 = 0.141, p = 0.041, and R2 = 0.311, p = 0.025, respectively). Nonperfusion predominance was not statistically correlated with the presence of macular edema (p = 0.058) or disorganization of retinal inner layers (p = 1). In the severe NPDR group, there was a moderately positive correlation between CNP index and CST (rs = 0.496, p = 0.019) and no correlation between CNP index and SCVA when controlling for CST (p = 0.160). In the PDR group, a strong negative correlation between PNP ratio and CST was found (rs = -0.659, p = 0.014), but no correlation was observed between CNP index, CST, and SCVA. In the PDR group, a positive correlation was found between PNP index, PNP ratio, and SCVA (rs = 0.549, p = 0.027, and rs = 0.626, p = 0.010, respectively), even after controlling for CST (rs = 0.599, p = 0.040). CONCLUSIONS: Higher amounts of retinal nonperfusion are seen in patients with more severe retinopathy. Increased CNP is associated with macular thickening and subsequent vision loss. Having predominantly PNP was independently associated with worse VA, regardless of macular thickness. Further studies are needed to investigate the role of PNP in vision loss in diabetic retinopathy.
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Diabetes Mellitus , Retinopatia Diabética , Estudos Transversais , Retinopatia Diabética/diagnóstico , Angiofluoresceinografia , Humanos , Prognóstico , Retina , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência ÓpticaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Purpose: Neonatal retinal folds and/or vitreoretinal traction can be signs of isolated ocular or syndromic disorders. Etiologies include retinopathy of prematurity, perinatal infections or inherited vitreoretinal disorders such as familial exudative vitreoretinopathy (FEVR) or Norrie disease. We present the clinical and genetic findings of a two-month-old infant with microcephaly, mild motor developmental delay, and FEVR, who required urgent surgical interventions.Methods: The patient underwent an initial examination under anesthesia (EUA) with fluorescein angiography (FA) and subsequent medical and surgical treatments. Genetic testing was undertaken to identify the etiology.Results: Examination at 2 months of age demonstrated microcephaly with a head circumference smaller than the 1st percentile. Family history was negative for microcephaly or retinal disease. Anterior segment eye exam was normal OU. There were bilateral macular folds involving the fovea and extending from the disc to the temporal periphery. FA demonstrated bilateral incomplete vascularization of the retina most notable nasally. Indirect laser was applied to ischemic retina OU. Scleral buckling procedures were performed OU as well as a vitrectomy in the left eye. Follow-up examinations demonstrated the stable appearance of the folds and attached retinas OU. Genetic testing identified a novel dominant heterozygous c.2046_2047del [p.Phe683Glnfs*9] mutation in CTNNB1, predicted to result in a frameshift causing a truncated protein.Conclusions: CTNNB1 mutations are an uncommon cause of FEVR with microcephaly.
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Vitreorretinopatias Exsudativas Familiares/etiologia , Mutação da Fase de Leitura , beta Catenina/genética , Vitreorretinopatias Exsudativas Familiares/patologia , Vitreorretinopatias Exsudativas Familiares/cirurgia , Humanos , Lactente , Masculino , PrognósticoRESUMO
PURPOSE: To study the anatomical and surgical prognostic factors related to developing postoperative intraretinal cystoid spaces (ICS) six months after 25-gauge pars plana vitrectomy (PPV) for vitreomacular traction (VMT). METHODS: The study is a retrospective case series of patients presenting with VMT treated primarily with PPV. All patients underwent 25-gauge PPV by the same retina surgeon. Intra-operative parameters were all recorded. Postoperative visual acuity (VA), foveal thickness, and ICS were collected over six months of follow-up. ICS were defined as hyporeflective cysts divided by hyperreflective septa on optical coherence tomography (OCT). Patients with ICS persistence 3 months postoperatively received topical treatment extension. The primary outcome measure was odds of preoperative ICS in patients with postoperative ICS compared to controls. Secondary outcome measures were odds of presence of an attached hyaloid to the optic disc, presence of pseudophakia, the use of intra-operative air, and the use of more than one intra-operative indocyanine green (ICG) injections in patients with postoperative ICS compared to controls. RESULTS: Two hundred and eighty treatment-naïve patients with preoperative diagnosis of epiretinal membrane (ERM) were reviewed. Thirty patients with VMT, confirmed both preoperatively on OCT and intra-operatively, were included. Postoperatively, 40% (n = 12) presented with ICS at 6 months. Among these, 83% (n = 10) had ICS prior to PPV. Patients presenting with preoperative ICS were significantly more at risk of having persistent ICS postoperatively (P < 0.05). The following factors did not statistically affect ICS occurrence: optic disc hyaloid attachment status, phakia/pseudophakia, intra-operative air vs. sulfur hexafluoride (SF6), and the number of intra-operative ICG injections. CONCLUSIONS: Our data demonstrate a predictive relationship between the occurrence/persistence of ICS post-PPV for VMT and the initial foveal status. Specifically, having preoperative ICS is a major risk factor for its persistence postoperatively. Our data highlight the pathophysiological importance of the vitreous phase and its effect on visual prognosis.
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Introduction: Mutations in Kizuna (KIZ), a gene involved in ciliary function, have been previously associated with rod-cone dystrophy with relative macular sparing and a number of other systemic abnormalities.Purpose: We present a patient with a phenotype dominated by retinal dystrophy and macular cysts as a result of a homozygous nonsense mutation in KIZ.Methods: A 32-year-old female of Ashkenazi Jewish ancestry presented with progressive central vision loss and peripheral visual field loss following decades of night-blindness. She was noted to have a bull's-eye pattern of macular hyper-autofluorescence, intraretinal cystoid macular changes and outer retinal atrophy in both eyes. Visual fields were constricted to <10 degrees centrally with inferior preserved islands of vision. Genetic testing revealed a homozygous KIZ c.226 C > T (p.Arg76*) nonsense mutation. The patient was treated with topical dorzolamide and showed significant improvement in the degree of macular cysts.Conclusion: Mutations in KIZ can present with a predominantly macular phenotype and develop cystoid macular changes responsive to carbonic anhydrase inhibitor treatment. Because of the importance of KIZ in cilia function, it is critical to look for associated systemic manifestations to ensure best patient care.
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Proteínas de Ciclo Celular/genética , Códon sem Sentido , Cistos/etiologia , Homozigoto , Edema Macular/etiologia , Distrofias Retinianas/complicações , Adulto , Cistos/patologia , Feminino , Humanos , Edema Macular/patologia , Masculino , Linhagem , Fenótipo , Prognóstico , Distrofias Retinianas/genética , Acuidade VisualRESUMO
PURPOSE OF REVIEW: The literature regarding prophylactic treatment of rhegmatogenous retinal detachment in Stickler syndrome remains controversial. We review major published clinical studies and offer a critical analysis of this subject. SUMMARY: Stickler syndrome is a systemic collagenopathy affecting multiple organ systems including the eye, ear, and skeleton. Stickler syndrome is probably the most common cause of genetically determined pediatric rhegmatogenous retinal detachment. Congenital developmental anomalies constitute over half rhegmatogenous detachments (RRD) in patients less than 10 years. The majority are caused by hereditary vitreoretinopathies associated with Stickler syndrome. Sixty percent of patients with Stickler syndrome develop RRD's over their lifetime with possible severe visual loss and subsequent lifelong morbidity. In view of these complications, some have emphasized the importance of prophylactic laser treatment to the retina of patients with Stickler syndrome to reduce the occurrence of and/or prevent future rhegmatogenous retinal detachment, but there appears to be insufficient data to support the absolute benefit of such prophylactic treatment. Guidelines regarding the age at prophylactic treatment as well as type and frequency of intervention are scarce and would benefit from additional clinical investigations.
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Artrite/complicações , Doenças do Tecido Conjuntivo/complicações , Perda Auditiva Neurossensorial/complicações , Descolamento Retiniano/prevenção & controle , Criança , Feminino , Humanos , Masculino , Descolamento Retiniano/complicações , Descolamento Retiniano/etiologiaRESUMO
Leber hereditary optic neuropathy (LHON) is a syndrome of subacute loss of central vision associated with mutations in mitochondrial DNA coding for components of complex I. LHON preferentially involves small axons in the temporal optic nerve, but the reason is unclear. We performed a Monte Carlo simulation of the spread of injury in LHON axons to better understand the predilection for small axons. Optic nerve slices were modeled as grids containing axons with sizes from reported regional distributions. The propagation of injury from a localized concentration of superoxide was simulated as the spread via passive diffusion from one axon to adjacent axons, with basal production and scavenging rate proportional to axonal area and volume, respectively. Axonal degeneration occurred when intra-axonal concentrations reached a toxic threshold. Simulations demonstrated that almost all small and medium axons degenerated by the time steady-state was reached, but about 50% of large axons were preserved. The location of initial injury affected time to steady state, with nasal injuries reaching steady state faster than temporal injuries. The pattern of axonal degeneration in the simulations mirrored both visual fields and optic nerve histology from patients with LHON. These results provide insight into the nature of axonal loss in LHON.
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Axônios/patologia , Modelos Neurológicos , Atrofia Óptica Hereditária de Leber/patologia , Axônios/metabolismo , Simulação por Computador , Humanos , Nervo Óptico/patologia , Reprodutibilidade dos Testes , Superóxidos/metabolismoRESUMO
Purpose: To describe the genotypes and phenotypes of ten patients with sector retinitis pigmentosa (RP). We also review previously reported mutations associated with sector RP and provide a discussion of possible underlying pathophysiological mechanisms. Methods: Patients underwent detailed ophthalmologic examinations, fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), as well as visual field and electroretinographic testing. All patients underwent genetic testing to identify the molecular etiology of their disease. Results: A total of ten patients were studied. Among these patients, nine had mutations in RHO (c.677T>C; p.Leu226Pro (novel), c.68C>A; p.Pro23His, c.808A>C; p.Ser270Arg, c.44A>G; p.Asn15Ser, and c.325G>A; p.Gly109Arg), and one patient had a mutation in RPGR (c.3092_3093delAG; p.Glu1031Glyfs*47). All patients with missense mutations in RHO had visual acuities (VAs) better than 20/30 and showed a retained foveal ellipsoid zone and overlying retinal structures. The patient with the c.3092_3093delAG deletion in RPGR had VA of 20/60 oculus dexter (OD) and 20/400 oculus sinister (OS), as well as significant foveal thinning and contour atrophy. All patients showed pigmentary changes, or marked atrophy along the inferior arcades, or both. This pattern of degeneration corresponded to hypo- and hyperFAF and superior visual defects. Conclusions: Sector RP is an uncommon form of RP in which only one or two retinal quadrants display clinical pathological signs. The great majority of cases result from mutations in RHO. The present data confirmed previously reported phenotypic manifestations of sector RP. Inferior retinal quadrants are possibly more severely affected due to greater light exposure.
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Retinose Pigmentar/genética , Sequência de Aminoácidos , Animais , Humanos , Mutação/genética , Fenótipo , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/diagnóstico por imagem , Retinose Pigmentar/fisiopatologia , Rodopsina/química , Rodopsina/genética , Campos VisuaisRESUMO
Significant discoveries in the etiology and pathogenesis of inherited retinal diseases (IRDs) have been made in the last few decades. Of the large number genes that cause IRDs, bi-allelic mutations in RPE65 lead to Leber Congenital Amaurosis type 2 (LCA 2), and can also result in phenotypes described as severe early childhood onset retinal dystrophy (SECORD) and Retinitis pigmentosa 20 (RP20). Following the publication of the successful Phase-III clinical trials of gene augmentation surgery for RPE65-related IRDs with voretigene neparvovec, the FDA approved the commercial use of this pharmacologic agent in December 2017. In this perspective, ongoing and completed gene therapy trials for RPE65-related dystrophies are reviewed and challenges in patient selection, counseling and informed consent, as well as financial considerations of commercial treatment are discussed.