Optic Disc and Retinal Architecture Changes in Patients with Spinocerebellar Ataxia Type 2.

BACKGROUND: ATXN2 is the causative gene of spinocerebellar ataxia type 2 (SCA2) and has been implicated in glaucoma pathogenesis. Therefore, studying ocular changes in SCA2 could uncover clinically relevant changes. OBJECTIVE: The aim was to investigate optic disc and retinal architecture in SCA2. METHODS: We evaluated 14 patients with SCA2 and 26 controls who underwent intraocular pressure measurement, fundoscopy, and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We compared SD-OCT measurements in SCA2 and controls, and the frequency of glaucomatous changes among SCA2, controls, and 76 patients with other SCAs (types 1, 3, 6, and 7). RESULTS: The macula, peripapillary retinal nerve fiber and inner plexiform layers were thinner in SCA2 than in controls. Increased cup-to-disc ratio was more frequent in SCA2 than in controls and other SCAs. CONCLUSIONS: Ocular changes are part of SCA2 phenotype. Future studies should further investigate retinal and optic nerve architecture in this disorder.

Characterization of Retinal Architecture in Spinocerebellar Ataxia Type 3 and Correlation with Disease Severity.

BACKGROUND: Neurodegeneration affects the brain and peripheral nervous system in spinocerebellar ataxia type 3 (SCA3). As the retina is also involved, studying the retinal architecture in a cohort of patients could reveal clinically relevant biomarkers. OBJECTIVE: The aim is to investigate retinal architecture in SCA3 to identify potential biomarkers. METHODS: We evaluated 38 patients with SCA3 and 25 healthy age-matched controls, who underwent visual acuity assessment, intraocular pressure measurement, and fundoscopy and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We measured the peripapillary retinal nerve fiber layer (pRNFL) thickness in each quadrant of the temporal-superior-nasal-inferior-temporal chart and the macular layer thicknesses in each sector of the inner circle of the Early Treatment Diabetic Retinopathy Study (IC-ETDRS) grid. Linear regression analysis was employed to test the associations between retinal parameters and age, disease duration, CAG repeats, and SARA (Scale of the Assessment and Rating of Ataxia) and ICARS (International Cooperative Ataxia Rating Scale) scores in SCA3. RESULTS: In all sectors, except for the temporal quadrant, pRNFL was significantly thinner in SCA3 patients than in controls. Average total macular, ganglion cell layer (GCL), and inner plexiform layer (IPL) thicknesses were significantly decreased in SCA3 patients in comparison to controls. The average total macular thickness and the average thicknesses of RNFL, GCL, and IPL negatively correlated with ICARS scores, whereas average GCL and IPL thicknesses negatively correlated with SARA scores. CONCLUSIONS: The retinal ganglion cells, their dendrites, and axons are selectively affected in SCA3 patients. The RNFL, GCL, and IPL thicknesses in SD-OCT correlate with the clinical phenotype and represent potential biomarkers for future clinical trials and natural history studies. © 2021 International Parkinson and Movement Disorder Society.

Retinal Architecture in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Insights into Disease Pathogenesis and Biomarkers.

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) causes unique retinal abnormalities, which have not been systematically investigated. OBJECTIVE: To deeply phenotype the retina in ARSACS in order to better understand its pathogenesis and identify potential biomarkers. METHODS: We evaluated 29 patients with ARSACS, 66 with spinocerebellar ataxia (SCA), 38 with autosomal recessive cerebellar ataxia (ATX), 22 with hereditary spastic paraplegia (SPG), 21 cases of papilledema, and 20 healthy controls (total n = 196 subjects). Participants underwent visual acuity assessment, intraocular pressure measurement, fundoscopy, and macular and peripapillary optical coherence tomography (OCT). Macular layers thicknesses in ARSACS were compared with those of age-matched healthy controls. Ophthalmologists analyzed the scans for abnormal signs in the different patient groups. Linear regression analysis was conducted to look for associations between retinal changes and age, age at onset, disease duration, and Scale for the Assessment and Rating of Ataxia (SARA) scores in ARSACS. RESULTS: Only patients with ARSACS exhibited peripapillary retinal striations (82%) on fundoscopy, and their OCT scans revealed foveal hypoplasia (100%), sawtooth appearance (89%), papillomacular fold (86%), and macular microcysts (18%). Average peripapillary retinal nerve fiber layer (pRNFL) was thicker in ARSACS than in SCA, ATX, SPG, and controls; a cut-off of 121 µm was 100% accurate in diagnosing ARSACS. All macular layers were thicker in ARSACS when compared to healthy controls. RNFL thickness in the inferior sector of the macula positively correlated with SARA scores. CONCLUSIONS: Retinal abnormalities are highly specific for ARSACS, and suggest retinal hyperplasia due to abnormal retinal development. OCT may provide potential biomarkers for future clinical trials. © 2021 International Parkinson and Movement Disorder Society.

A Proposal for Classification of Retinal Degeneration in Spinocerebellar Ataxia Type 7.

The aim of this study is to propose a classification system for the spinocerebellar ataxia type 7 retinal degeneration (SCA7-RD). Twenty patients with molecularly confirmed SCA7 underwent slit lamp examination, fundus photography, and optical coherence tomography (Spectralis®). Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale (ICARS) were applied, and age, sex, age at symptom onset, and number of CAG expansions were recorded. After analyzing the ophthalmological findings in each participant, a panel of retinal disease experts created a qualitative classification system for SCA7-RD comprising four stages. We assessed the correlations of retinal degeneration severity with SARA and ICARS scores, number of CAG repeats in ATXN7 allele, and age at symptom onset. We graded retinal degeneration as stage 1 in nine participants, as stage 2 in five, and as stage 3 in six. No differences in age and visual symptoms duration were found between groups. SARA and ICARS scores correlated with the severity of SCA7-RD on the classification system (p = 0.024 and p = 0.014, respectively). After adjusting for disease duration, retinal disease stage association with SARA and ICARS scores remained significant (ANCOVA, p < 0.05). The classification system for SCA7-RD was able to characterize different disease stages representing the landmarks in the cone-rod dystrophy natural history. Neurodegeneration appears to occur in parallel in the cerebellum and in the visual pathway. We conclude that retinal degeneration in SCA7 is a potential biomarker of the neurological phenotype severity.

VALUE OF CLINICAL, LABORATORY PARAMETERS AND ANALYSIS OF RETINAL VASCULARIZATION IN PEDIATRIC PATIENTS WITH PORTAL HYPERTENSION.

BACKGROUND: Portal hypertension is one of the complications of cirrhosis and is associated with numerous systemic manifestations, including renal, brain, pulmonary, cardiac and vascular changes. In routine ophthalmological examinations performed at our service, we observed that some children diagnosed with portal hypertension had increased retinal vascular tortuosity. OBJECTIVE: 1. To evaluate the presence of retinal vascular abnormalities (vascular tortuosity) in children diagnosed with portal hypertension; 2. To investigate the association between retinal vascular tortuosity and the presence of gastroesophageal varices in these children; 3. To evaluate the use of clinical and laboratory parameters to predict the presence of gastroesophageal varices in children with portal hypertension. METHODS: This was a cross-sectional and observational study that included patients aged <18 years with a diagnosis of portal hypertension. The participants included were submitted to dilated fundus examination and fundus photography with Visucam (Carl Zeiss Meditec AG) device. Besides, clinical and laboratorial data were collected from the patients' medical records. RESULTS: A total of 72 patients were included in this study, and 36% of them had an increase in retinal vascular tortuosity. Platelet count (P=0.001), bilirubin dosage (P=0.013) and aspartate transaminase dosage (AST) (P=0.042) were associated with the presence of gastroesophageal varices in digestive endoscopy. There was no association between retinal vascular tortuosity and the presence of gastroesophageal varices (P=0.498). CONCLUSION: The results of this study suggest that platelet count, bilirubin dosage, and aspartate transaminase dosage were associated with the presence of gastroesophageal varices in digestive endoscopy. Regarding the retinal findings, we found that there was an increase in retinal vascular tortuosity in 36% of pediatric patients, but no association was found with the presence of gastroesophageal varices.

Valor de parâmetros clínicos, laboratoriais e análise da vascularização da retina em pacientes pediátricos com hipertensão portal / Value of clinical, laboratory parameters and analysis of retinal vascularization in pediatric patients with portal hypertension

ABSTRACT BACKGROUND: Portal hypertension is one of the complications of cirrhosis and is associated with numerous systemic manifestations, including renal, brain, pulmonary, cardiac and vascular changes. In routine ophthalmological examinations performed at our service, we observed that some children diagnosed with portal hypertension had increased retinal vascular tortuosity. OBJECTIVE: 1. To evaluate the presence of retinal vascular abnormalities (vascular tortuosity) in children diagnosed with portal hypertension; 2. To investigate the association between retinal vascular tortuosity and the presence of gastroesophageal varices in these children; 3. To evaluate the use of clinical and laboratory parameters to predict the presence of gastroesophageal varices in children with portal hypertension. METHODS: This was a cross-sectional and observational study that included patients aged <18 years with a diagnosis of portal hypertension. The participants included were submitted to dilated fundus examination and fundus photography with Visucam (Carl Zeiss Meditec AG) device. Besides, clinical and laboratorial data were collected from the patients' medical records. RESULTS: A total of 72 patients were included in this study, and 36% of them had an increase in retinal vascular tortuosity. Platelet count (P=0.001), bilirubin dosage (P=0.013) and aspartate transaminase dosage (AST) (P=0.042) were associated with the presence of gastroesophageal varices in digestive endoscopy. There was no association between retinal vascular tortuosity and the presence of gastroesophageal varices (P=0.498). CONCLUSION: The results of this study suggest that platelet count, bilirubin dosage, and aspartate transaminase dosage were associated with the presence of gastroesophageal varices in digestive endoscopy. Regarding the retinal findings, we found that there was an increase in retinal vascular tortuosity in 36% of pediatric patients, but no association was found with the presence of gastroesophageal varices.

RESUMO CONTEXTO: A hipertensão portal é uma das complicações da cirrose e está associada a inúmeras manifestações sistêmicas, incluindo alterações renais, cerebrais, pulmonares, cardíacas e vasculares. Nos exames oftalmológicos de rotina realizados em nosso serviço, observamos que algumas crianças diagnosticadas com hipertensão portal apresentaram aumento da tortuosidade vascular da retina. OBJETIVO: 1. Avaliar a presença de anormalidades vasculares da retina (tortuosidade vascular) em crianças diagnosticadas com hipertensão portal; 2. Investigar a associação entre tortuosidade vascular da retina e presença de varizes gastroesofágicas nessas crianças; 3. Avaliar o uso de parâmetros clínicos e laboratoriais para prever a presença de varizes gastroesofágicas em crianças com hipertensão portal. MÉTODOS: Estudo transversal e observacional, que incluiu pacientes com idade <18 anos com diagnóstico de hipertensão portal. Os participantes incluídos foram submetidos ao exame de fundo de olho dilatado e fotografia de fundo com dispositivo Visucam (Carl Zeiss Meditec AG). Além disso, foram coletados dados clínicos e laboratoriais dos prontuários dos pacientes. RESULTADOS: Um total de 72 pacientes foi incluído neste estudo e 36% deles apresentaram aumento da tortuosidade vascular da retina. Contagem de plaquetas (P=0,001), dosagem de bilirrubina (P=0,013) e dosagem de aspartato transaminase (AST) (P=0,042) foram associados à presença de varizes gastroesofágicas na endoscopia digestiva. Não houve associação entre tortuosidade vascular da retina e presença de varizes gastroesofágicas (P=0,498). CONCLUSÃO: Os resultados deste estudo sugerem que a contagem de plaquetas, a dosagem de bilirrubina e a aspartato transaminase foram associadas à presença de varizes gastroesofágicas na endoscopia digestiva. Em relação aos achados da retina, descobrimos que houve um aumento na tortuosidade vascular da retina em 36% dos pacientes pediátricos, mas nenhuma associação foi encontrada com a presença de varizes gastroesofágicas.

Impact of manual correction over automated segmentation of spectral domain optical coherence tomography.

OBJECTIVE: To study the automated segmentation of retinal layers using spectral domain optical coherence tomography (OCT) and the impact of manual correction over segmentation mistakes. METHODS: This was a retrospective, cross-sectional, comparative study that compared the automated segmentation of macular thickness using Spectralis™ OCT technology (Heidelberg Engineering, Heidelberg, Germany) versus manual segmentation in eyes with no macular changes, macular cystoid edema (CME), and choroidal neovascularization (CNV). Automated segmentation of macular thickness was manually corrected by two independent examiners and reanalyzed by them together in case of disagreement. RESULTS: In total, 306 eyes of 254 consecutive patients were evaluated. No statistically significant differences were noted between automated and manual macular thickness measurements in patients with normal maculas, while a statistically significant difference was found in central thickness in patients with CNV and with CME. Segmentation mistakes in macular OCTs were present in 5.3% (5 of 95) in the normal macula group, 16.4% (23 of 140) in the CME group, and 66.2% (47 of 71) in CNV group. The difference between automated and manual macular thickness was higher than 10% in 1.4% (2 of 140) in the CME group and in 28.17% (20 of 71) in the CNV group. Only one case in the normal group had a higher than 10% segmentation error (1 of 95). CONCLUSION: The evaluation of automated segmented OCT images revealed appropriate delimitation of macular thickness in patients with no macular changes or with CME, since the frequency and magnitude of the segmentation mistakes had low impact over clinical evaluation of the images. Conversely, automated macular thickness segmentation in patients with CNV showed a high frequency and magnitude of mistakes, with potential impact on clinical analysis.

Observational study of intraocular lens tilt in sutureless intrascleral fixation versus standard transscleral suture fixation determined by ultrasound biomicroscopy.

BACKGROUND: The position of the intraocular lens (IOL) is a major factor that affects the final visual acuity after cataract surgery. However, no prospective study has compared the IOL positions associated with the sutureless intrascleral technique and the standard transscleral suturing technique. The current study compared the IOL positions in the two techniques using ultrasound biomicroscopy (UBM) in vivo. METHODS: Twenty-one eyes of 21 patients were included in this observational study conducted between February and May 2015. Eleven patients underwent the sutureless intrascleral technique, and 10 patients underwent transscleral fixation with suturing. Ophthalmologic examination and UBM were performed in all patients. Optic tilt was measured in relation to the iris plane. The haptic location was defined. Mann-Whitney test and multiple linear regression were used to analyze the vertical and horizontal gradients. Significant differences were considered when p ≤ 0.05. RESULTS: The most common indication for scleral fixation was a complication during phacoemulsification (81.81% in the sutureless group and 60% in the suture group). The mean vertical and horizontal tilts were, respectively, 0.24 ± 0.21 and 0.25 ± 0.19 mm in the sutureless group and 0.14 ± 0.17 and 0.23 ± 0.16 mm in the suture group. No significant differences were seen in the vertical tilt and horizontal tilt (p = 0.888 and p = 0.148, respectively) between the groups. Gender (p = 0.835), age (p = 0.888), follow-up time (p = 0.915), and surgical duration (p = 0.094) were not associated with optic tilt. Of the 22 haptics in the sutureless group, 21 (95.45%) were in the intrascleral tunnel; of the 20 haptics in the suture group, 13 (65%) were posterior to the ciliary body, four (20%) anterior to the ciliary body, and three (15%) in the ciliary sulcus. CONCLUSION: This study showed that there are no significant differences in the IOL positions between the two techniques.