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PURPOSE: The aim of this study was to explore the potential benefits of retinal pigment epithelium replacement therapy in patients with Bietti crystalline dystrophy (BCD) by assessing the disease pathology with the distinctive relationship between fundus autofluorescence (FAF) abnormality and visual field defect. METHODS: Sixteen eyes from 16 patients with BCD and 16 eyes from 16 patients with RHO-associated retinitis pigmentosa were included. Fundus autofluorescence, optical coherence tomography, and Goldmann perimetry results were retrospectively reviewed and assessed using image analyses. RESULTS: In patients with BCD, the FAF abnormality area was not correlated with the overall visual field defect area and median overall visual field defect area (57.5%) was smaller than FAF abnormality area (98.5%). By contrast, the ellipsoid zone width was significantly correlated with the central visual field area (r = 0.806, P < 0.001). In patients with RHO-associated retinitis pigmentosa, the FAF abnormality area and ellipsoid zone width were significantly correlated with the overall visual field defect area (r = 0.833, P < 0.001) and central visual field area (r = 0.887, P < 0.001), respectively. CONCLUSION: The FAF abnormality shown in patients with BCD involves retinal pigment epithelium degeneration without complete loss of photoreceptors or visual function. These results suggest that patients with BCD are good candidates for retinal pigment epithelium replacement therapy for preservation of residual visual function.
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Distrofias Hereditárias da Córnea , Angiofluoresceinografia , Fundo de Olho , Epitélio Pigmentado da Retina , Tomografia de Coerência Óptica , Acuidade Visual , Testes de Campo Visual , Campos Visuais , Humanos , Campos Visuais/fisiologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/fisiopatologia , Angiofluoresceinografia/métodos , Adulto , Epitélio Pigmentado da Retina/patologia , Idoso , Acuidade Visual/fisiologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/fisiopatologia , Transtornos da Visão/fisiopatologia , Transtornos da Visão/diagnóstico , Imagem Óptica , Retinose Pigmentar/fisiopatologia , Retinose Pigmentar/diagnóstico , Adulto JovemRESUMO
BACKGROUND: This study aimed to identify the features of ocular biometry in patients with EYS-related retinitis pigmentosa using IOLMaster 700. METHODS: We retrospectively reviewed the medical records of patients with retinitis pigmentosa. Patients with records of the following were included: (1) ocular biometry measurements using the IOLMaster 700 and (2) genetic diagnostic tests. Axial length, keratometry, anterior chamber depth, aqueous depth, lens thickness, central corneal thickness (CCT), and corneal diameter (white to white) measurements were extracted. Based on keratometry measurements, (1) standard keratometric astigmatism, (2) posterior corneal astigmatism, and (3) total corneal astigmatism were obtained. Demographics and biometric parameters were compared between patients with EYS-related retinitis pigmentosa and other patients with retinitis pigmentosa. RESULTS: A total of 86 eyes of 44 patients (23 females and 21 males; mean age: 47.7 years) with retinitis pigmentosa were included. Of these, 18 were identified as having EYS variants. CCT was significantly thinner (P < 0.001) and the posterior corneal curvature at the steepest meridian was significantly smaller (P = 0.024) in patients with EYS-related retinitis pigmentosa than in other patients with retinitis pigmentosa. The magnitudes of all corneal astigmatism measurements was higher in patients with EYS-related RP, although these differences were not statistically significant. CONCLUSION: Patients with EYS-related retinitis pigmentosa had unique features in ocular biometry, such as thinner central corneal thickness and smaller posterior corneal curvature radius at the steepest meridian compared with other patients with retinitis pigmentosa. The findings suggest that patients with retinitis pigmentosa have different ocular dimension features among the different causative genes.
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Retinose Pigmentar , Tomografia de Coerência Óptica , Comprimento Axial do Olho/anatomia & histologia , Comprimento Axial do Olho/diagnóstico por imagem , Biometria , Proteínas do Olho , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate tangential morphological changes in the outer retina and assess their correlation with the degree of metamorphopsia in patients with idiopathic epiretinal membrane (ERM). METHODS: This retrospective study included patients with idiopathic ERM who underwent vitrectomy between January 2018 and December 2019. We evaluated the preoperative examination results. Using cross-sectional spectral-domain optical coherence tomography (OCT) images along the horizontal/vertical meridian through the fovea, we defined a new parameter, tangential displacement (TD), as the tangential component of the position vector of the distorted outer nuclear layer caused by ERM. Visual function measurements included M-CHARTS results (vertical/horizontal metamorphopsia score [MV/MH]) and best-corrected visual acuity (BCVA). The correlations among the OCT parameters including TD and central foveal thickness (CFT) with visual function measurements were determined. RESULTS: Overall, 78 eyes of 76 patients (49 females; mean age, 67.9 [± standard deviation, 7.5 years]) were included. The mean horizontal TD was 24.0 ± 73.9 µm, which was significantly different from 0 (p = 0.005). The mean vertical TD was 6.0 ± 76.2 µm, which was not significantly different from 0. The absolute value of horizontal TD was significantly correlated with MV (r = 0.513, p < 0.01) and MH (r = 0.423, p < 0.01). The absolute value of vertical TD was also significantly correlated with MV (r = 0.274, p = 0.02) and MH (r = 0.413, p < 0.01). However, neither value was significantly correlated with BCVA. Multiple regression analysis showed that the horizontal absolute TD was an independent factor associated with both MV (ß = 0.635, p < 0.001) and MH (ß = 0.259, p = 0.048). CONCLUSION: We found that ERM tended to distort the outer retinal layer toward the temporal side of the fovea. The tangential distortion of this layer was associated with the degree of metamorphopsia, suggesting that misalignment of parafoveal photoreceptors causes metamorphopsia in patients with ERM.
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Membrana Epirretiniana , Idoso , Estudos Transversais , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Feminino , Humanos , Retina , Estudos Retrospectivos , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico , Acuidade Visual , VitrectomiaRESUMO
We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).
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Células-Tronco Pluripotentes Induzidas/citologia , Degeneração Macular/terapia , Epitélio Pigmentado da Retina/citologia , Idoso , Técnicas de Cultura de Células , Diferenciação Celular , Estudos de Viabilidade , Feminino , Fibroblastos , Humanos , Masculino , Epitélio Pigmentado da Retina/transplante , Transplante AutólogoRESUMO
USH2A is a common causal gene of retinitis pigmentosa (RP), a progressive blinding disease due to retinal degeneration. Genetic alterations in USH2A can lead to two types of RP, non-syndromic and syndromic RP, which is called Usher syndrome, with impairments of vision and hearing. The complexity of the genotype-phenotype correlation in USH2A-associated RP (USH2A-RP) has been reported. Genetic and clinical characterization of USH2A-RP has not been performed in Japanese patients. In this study, genetic analyses were performed using targeted panel sequencing in 525 Japanese RP patients. Pathogenic variants of USH2A were identified in 36 of 525 (6.9%) patients and genetic features of USH2A-RP were characterized. Among 36 patients with USH2A-RP, 11 patients had syndromic RP with congenital hearing problems. Amino acid changes due to USH2A alterations were similarly located throughout entire regions of the USH2A protein structure in non-syndromic and syndromic RP cases. Notably, truncating variants were detected in all syndromic patients with a more severe retinal phenotype as compared to non-syndromic RP cases. Taken together, truncating variants could contribute to more serious functional and tissue damages in Japanese patients, suggesting important roles for truncating mutations in the pathogenesis of syndromic USH2A-RP.
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Proteínas da Matriz Extracelular/genética , Perda Auditiva/genética , Doenças Retinianas/genética , Adulto , Idade de Início , Idoso , Povo Asiático/genética , Proteínas da Matriz Extracelular/química , Proteínas da Matriz Extracelular/metabolismo , Feminino , Estudos de Associação Genética , Variação Genética , Perda Auditiva/congênito , Perda Auditiva/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/etiologia , Retinose Pigmentar/genética , Síndromes de Usher/genética , Acuidade Visual/genéticaRESUMO
Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro "drug-lymphocytes-grafts immune reaction (Drug-LGIR)" test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of Drug-LGIR, we applied cyclosporine A or local steroid (triamcinolone) therapy to two monkeys, and successfully suppressed RPE-related immune rejections with RPE grafts, which survived without any signs of rejection under drug administration. We propose that our new preoperational in vitro Drug-LGIR test, which specifies the most efficacious medication for each recipient, is useful for controlling immune attacks with personalized treatment for each patient after retinal transplantation.
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Células Epiteliais , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/terapia , Células-Tronco Pluripotentes Induzidas , Medicina de Precisão , Epitélio Pigmentado da Retina/citologia , Transplante de Células-Tronco , Animais , Biomarcadores , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Ciclosporina/administração & dosagem , Modelos Animais de Doenças , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Xenoenxertos , Humanos , Imuno-Histoquímica , Imunofenotipagem , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Macaca fascicularis , Complicações Pós-Operatórias , Medicina de Precisão/métodos , Epitélio Pigmentado da Retina/metabolismo , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/métodos , Esteroides/administração & dosagem , Transplante Heterólogo , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to investigate the deformation of the outer nuclear layer using optical coherence tomography in patients with epiretinal membrane (ERM) and its relationship with metamorphopsia. METHODS: Thirty-nine eyes from 39 patients with ERM were included in the study. Patients with the subtypes of pseudo macula hole and lamellar hole were excluded. Twenty-one fellow eyes without macular disease were included as normal controls. Forty-nine B-scan images were obtained in the range of 20 degrees around the macula using SD-OCT. The outer nuclear layer (ONL) was evaluated as a three-dimensional image (3D-ONL) reconstructed using the distance between the ONL and retinal pigment epithelium (RPE) line. The deformation of the ONL was figured at the reference plane and evaluation plane (ONL-B). The characteristic parameters of the ONL-B were defined as circularity, area ratio, and axis ratio. The correlations between these parameters and visual acuity and MCHART score ratio (MH/MV) were then evaluated. RESULTS: ONL height was significantly higher in ERM patients than in normal controls (54.1 ± 5.3 µm and 84.1 ± 12.9 µm, respectively; P < 0.001). In ERM patients, the MV score was 0.53 ± 0.50, the MH score was 0.71 ± 0.61, and the distance from the RPE line to the ONL-B was 153.5 ± 13.5 µm. The axis of the ONL-B in normal controls and ERM patients was - 6.25 ± 21.8 and - 1.28 ± 29.1, respectively, which indicates that the ONL is horizontally long in both normal individuals and ERM patients. The circularity and area ratio were significantly smaller in ERM patients than in normal controls. In all ERM patients, MH/MV had a significant correlation with axis (r = - 0.29, p = 0.034), circularity (r = - 0.28, p = 0.044), and area ratio (r = - 0.47, p = 0.001). Moreover, we found that the correlation was more significant if the subjects had an axis of the ONL within ±10 degrees (n = 16); the correlations of MH/MV with axis (r = - 0.29, p = 0.034), circularity (r = - 0.53, p = 0.021), and area ratio were more significant (r = - 0.78, P < 0.0001). CONCLUSION: The ONL is horizontally long in normal individuals and ERM patients. The direction of metamorphopsia is correlated with the direction of ONL deformation.
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Membrana Epirretiniana/patologia , Retina/patologia , Transtornos da Visão/patologia , Idoso , Estudos de Casos e Controles , Membrana Epirretiniana/fisiopatologia , Feminino , Humanos , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologiaRESUMO
Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74-90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p.C759F in arRP and p.E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.
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Proteínas da Matriz Extracelular/genética , Genes Recessivos/genética , Mutação , Retinose Pigmentar/genética , Síndromes de Usher/genética , Povo Asiático/genética , Análise Mutacional de DNA , Éxons/genética , Saúde da Família , Feminino , Frequência do Gene , Genótipo , Humanos , Japão , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Retinose Pigmentar/etnologia , Retinose Pigmentar/patologia , População Branca/genéticaRESUMO
BACKGROUND: A prior phase I/IIa clinical trial provided evidence for safety, feasibility and potential efficacy of i.m. injection of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ cells in patients with critical limb ischemia (CLI). METHODS AND RESULTS: A phase II trial of CD34+ cell therapy was conducted in patients with CLI to explore endpoint selection and timing. No-option CLI patients (n=11) underwent i.m. transplantation of G-CSF-mobilized CD34+ cells isolated by magnetic sorting. Ischemic rest pain scales improved from week 2 vs. baseline (P<0.05). Skin perfusion pressure (P=0.0175), transcutaneous partial oxygen pressure (P=0.0446) and pain-free walking distance (P=0.0056) improved from week 2, total walking distance from week 8 (P=0.0182) and toe brachial pressure index from week 12 (P=0.0174) vs. baseline. These parameters peaked at week 36 or 52. Rutherford's category improved from week 24 vs. baseline (P=0.0065). CLI-free ratio serially increased and peaked (85.7%) at week 36. Serial change in Rutherford's category correlated with that in Rest Pain Scale (P=0.0374), but not with that in any physiological parameters. CONCLUSIONS: Ischemic rest pain scales and physiological parameters improved relatively early after cell therapy, then plateaued later accompanied by recovery from the CLI state. Rutherford's category and CLI-free ratio at week 36 or later may be suitable endpoints in cell therapy clinical trials for CLI. Functional parameters should be evaluated independently of such clinical endpoints for ischemia severity. ( CLINICAL TRIAL REGISTRATION: URL: https://dbcentre3.jmacct.med.or.jp/jmactr/Default.aspx. Unique identifier: JMA-IIA00022)
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Antígenos CD34 , Isquemia , Extremidade Inferior , Manejo da Dor , Dor/fisiopatologia , Transplante de Células-Tronco , Células-Tronco , Adulto , Idoso , Autoenxertos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Feminino , Humanos , Isquemia/fisiopatologia , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
This study evaluates the transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into patients with advanced retinitis pigmentosa using adaptive optics optical coherence tomography (AO-OCT) to monitor retinal changes over two years post transplantation. Our results confirmed successful engraftment and increased retinal thickness, with AO-OCT providing detailed visualization of cellular structures such as an outer plexiform layer-like line and highly reflective particles within rosette-like formations, indicative of photoreceptor development. Immunohistological analysis in a parallel monkey model confirmed these structures as mature, functional photoreceptor rosettes. The integration of high-resolution AO-OCT with immunohistology provides critical insights into the structural and functional outcomes of transplantation and represents a promising advancement in the treatment of retinal degenerative diseases.
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OBJECTIVE: Cystoid macular edema (CME) in retinitis pigmentosa (RP) is an important complication causing visual dysfunction. We investigated the effect of CME on photoreceptors in RP patients with previous or current CME, using an adaptive optics (AO) fundus camera. METHODS: We retrospectively observed the CME and ellipsoid zone (EZ) length (average of horizontal and vertical sections) by optical coherence tomography. The density and regularity of the arrangement of photoreceptor cells (Voronoi analysis) were examined at four points around 1.5° from superior to inferior and temporal to nasal. We also performed a multivariate analysis using CME duration, central macular thickness and transversal length of CME. RESULTS: We evaluated 18 patients with previous or current CME (18 eyes; age, 48.7 ± 15.6 years) and 24 patients without previous or current CME (24 eyes; age, 46.0 ± 14.5 years). There were no significant differences in age, logMAR visual acuity, or EZ length. In groups with and without CME, cell density was 11967 ± 3148 and 16239 ± 2935 cells/mm2, and sequence regularity was 85.5 ± 3.4% and 88.5 ± 2.8%, respectively; both parameters were significantly different. The correlation between photoreceptor density and age was more negative in group with CME. The CME group tended toward greater reductions in duration of CME. CONCLUSION: Complications of CME in RP patients may lead to a decrease in photoreceptor density and regularity. Additionally, a longer duration of CME may result in a greater reduction in photoreceptor density.
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Edema Macular , Retinose Pigmentar , Humanos , Adulto , Pessoa de Meia-Idade , Edema Macular/complicações , Estudos Retrospectivos , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico por imagem , Fóvea Central , Tomografia de Coerência Óptica/métodos , Células FotorreceptorasRESUMO
This study aimed to investigate how the extent and central/peripheral location of the residual visual field (VF) in patients with late-stage inherited retinal diseases (IRDs) are related to retinal sensitivity detected using full-field stimulus testing (FST). We reviewed the results of Goldmann perimetry and FST from the medical records of patients with IRDs whose VF represents central (within 10°) and/or peripheral islands, or undetectable. In total, 19 patients (19 eyes) were analyzed in this study. The median value of residual VF area was 1.38%. The median values of rod and cone sensitivities were - 14.9 dB and 7.4 dB, respectively. Patients with only the peripheral island (- 33.9 dB) had better median rod sensitivity than other groups (only central, - 18.9 dB; both, - 3.6 dB). VF area significantly correlated with rod sensitivity (r = - 0.943, p = 0.005) in patients with only peripheral island, but not with cone sensitivity. Peripheral VF islands were significant contributors to FST results, especially rod sensitivity. With reduced or loss of central vision, the extent of residual peripheral VF significantly affected rod sensitivity, suggesting that FST can be useful in quantitatively estimating the overall remaining vision in patients with late-stage IRD.
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Degeneração Retiniana , Campos Visuais , Humanos , Testes de Campo Visual/métodos , Adaptação à Escuridão , RetinaRESUMO
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy and a major cause of blindness. RP is caused by several variants of multiple genes, and genetic diagnosis by identifying these variants is important for optimizing treatment and estimating patient prognosis. Next-generation sequencing (NGS), which is currently widely used for diagnosis, is considered useful but is known to have limitations in detecting copy number variations (CNVs). In this study, we re-evaluated CNVs in EYS, the main causative gene of RP, identified via NGS using multiplex ligation-dependent probe amplification (MLPA). CNVs were identified in NGS samples of eight patients. To identify potential CNVs, MLPA was also performed on samples from 42 patients who were undiagnosed by NGS but carried one of the five major pathogenic variants reported in Japanese EYS-RP cases. All suspected CNVs based on NGS data in the eight patients were confirmed via MLPA. CNVs were found in 2 of the 42 NGS-undiagnosed RP cases. Furthermore, results showed that 121 of the 661 patients with RP had EYS as the causative gene, and 8.3% (10/121 patients with EYS-RP) had CNVs. Although NGS using the CNV calling criteria utilized in this study failed to identify CNVs in two cases, no false-positive results were detected. Collectively, these findings suggest that NGS is useful for CNV detection during clinical diagnosis of RP.
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Variações do Número de Cópias de DNA , Proteínas do Olho , Sequenciamento de Nucleotídeos em Larga Escala , Retinose Pigmentar , Humanos , Retinose Pigmentar/genética , Retinose Pigmentar/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Feminino , Masculino , Proteínas do Olho/genética , Pessoa de Meia-Idade , Adulto , Reação em Cadeia da Polimerase Multiplex/métodosRESUMO
OBJECTIVE: To predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa by measuring ellipsoid zone (EZ) width using spectral-domain optical coherence tomography. METHODS: This retrospective study included patients with retinitis pigmentosa who underwent uncomplicated cataract surgery between December 2017 and June 2020. Preoperative best-corrected visual acuity (BCVA) and the best postoperative BCVA during follow-up were collected. EZ width was measured on preoperative cross-sectional optical coherence tomography images along the horizontal/vertical meridian through the fovea. RESULTS: Thirty-eight eyes of 38 patients (22 female; mean [±standard deviation] age, 62.1 ± 11.8 years) were included. The median preoperative logarithm of the minimum angle of resolution BCVA of 0.52 (range, 0.00-3.00) significantly improved to 0.07 (range, -0.18-3.00) after surgery (P < 0.001). On preoperative spectral-domain optical coherence tomography images, the median horizontal, vertical, and average EZ widths were 783 (range, 0-9837), 761 (range, 0-10 250), and 769 (range, 0-10 043) µm, respectively. Postoperative BCVA significantly correlated with the horizontal (r = -0.784, P < 0.001), vertical (r = -0.777, P < 0.001), and average EZ widths (r = -0.777, P < 0.001). The area under the receiver operating characteristic curve for the ability of the horizontal, vertical, and average EZ widths to discriminate eyes with and without postoperative BCVA ≤ 0.3 was 0.971, 0.960, and 0.963, respectively, with best cut-off values of 513, 608, and 515 µm, respectively. CONCLUSIONS: EZ width measurement can help predict the visual prognosis of cataract surgery in patients with retinitis pigmentosa. A preferable visual acuity prognosis can be expected in patients with an EZ width of approximately 600 µm.
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Opacificação da Cápsula , Retinose Pigmentar , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos Transversais , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico , Retina , Prognóstico , Tomografia de Coerência Óptica/métodosRESUMO
PURPOSE: To describe a novel case of bilateral rapidly progressive retinopathy after immunotherapy with pembrolizumab for metastatic urothelial carcinoma. METHODS: Case report. RESULTS: A 64-year-old man undergoing pembrolizumab immunotherapy was referred to our hospital because of bilateral acute vision loss. His best-corrected visual acuity was 20/30 in the right eye and 20/320 in the left eye, and a visual field test revealed central and paracentral scotomas in the right eye and central scotoma in the left eye. We suspected immune-related retinopathy based on the progressive photoreceptor damage with abnormal electroretinogram findings, absence of overt intraocular inflammation, and presence of malignancy. Cessation of pembrolizumab and steroid pulse therapy followed by decreasing oral prednisolone improved visual function and photoreceptor damage, although there was recurrence after pembrolizumab was restarted. CONCLUSION: We reported a case of rapidly progressive retinopathy that may have been triggered by pembrolizumab immunotherapy for metastatic urothelial carcinoma. High-dose corticosteroid pulse therapy was effective in reversing photoreceptor damage.
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Carcinoma de Células de Transição , Doenças Retinianas , Neoplasias da Bexiga Urinária , Masculino , Humanos , Pessoa de Meia-Idade , Doenças Retinianas/induzido quimicamente , Cegueira , Escotoma , Imunoterapia/efeitos adversosRESUMO
PURPOSE: To identify the genotypic and phenotypic characteristics of rhodopsin (RHO)-associated retinitis pigmentosa (RP) in the Japanese population. STUDY DESIGN: Cross-sectional, single-center study METHODS: The medical records of 1336 patients with RP who underwent genetic testing at our clinic between November 2008 and September 2021 were reviewed, and patients with RHO variants were included. The patients were divided into class A and class B to assess genotype-phenotype correlations based on previous reports. The clinical findings, including best-corrected visual acuity (BCVA), OCT parameters (ellipsoid zone [EZ] width and central retinal thickness [CRT]), and presence of macular degeneration, of the 2 groups were compared. RESULTS: The study included 28 patients diagnosed with RHO-associated RP (class A, 19; class B, 9). The BCVA was significantly worse in class A patients than in class B patients (P = 0.045). Superior EZ width was significantly shorter in class A than in class B patients (P = 0.016). Class A patients tended to have thinner CRT and shorter inferior EZ width than those of class B patients, although this difference was not significant. Macular degeneration was observed in 61.5% of class A and 12.5% of class B patients, demonstrating that macular degeneration can be a common complication in class A variants. CONCLUSION: Patients with class A variants presented with a severer form of RP than that of patients with class B variants in the Japanese population. These results suggest that the phenotype of RHO-associated RP is linked to the location of the variants and that such a genotype-phenotype correlation is less affected by ethnicities with different genetic backgrounds.
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Degeneração Macular , Retinose Pigmentar , Humanos , Rodopsina/genética , Estudos Transversais , População do Leste Asiático , Tomografia de Coerência Óptica/métodos , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Fenótipo , GenótipoRESUMO
Purpose: Novel therapeutic options, such as regenerative medicine and gene therapy, are now emerging as viable treatment options for patients with severe visual impairments, such as retinitis pigmentosa (RP). Gradable assessment of patients' visual function is essential to consider treatment options and to evaluate treatment outcomes; however, evaluation of visual function in patients with advanced low vision is often challenging because of patients' poor and sometimes unpredictable responses. In this study, we attempted to accurately assess visual capabilities and disease stage in patients with RP with a visual acuity (VA) of ≤ 0.01. Design: Retrospective analysis of visual function indicators, including VA, retinal thickness, full-field stimulus testing (FST), and chromatic pupillometry. Subjects: Overall, 43 patients (84 eyes) with advanced RP with a VA of ≤ 0.01 visited Kobe City Eye Hospital from 2019 to 2021. Methods: Hierarchical (multilevel) Bayesian modeling was used to estimate individual eye's pupil response and FST threshold, taking into account the ambiguity and randomness often observed in patients with ultralow vision. Using the estimated ability obtained from each test, the correlation between each test and retinal thickness was further analyzed to make a comprehensive assessment of the data. Main Outcome Measures: Visual acuity, retinal thickness, FST threshold, and pupil diameter change to different light stimuli. Results: Full-field stimulus testing and pupillometry measurements were moderately correlated with VA but exhibited a wide range of values within the same VA groups. Full-field stimulus testing was not correlated with central retinal thickness at counting fingers/hand motion VA range and seemed to reflect overall remaining photoreceptor function, including peripheral retina. Pupillometry may be able to distinguish between different levels of inner retinal function. Conclusions: The combination of pupillometry and FST allowed for graded evaluation of visual function within patients grouped in the same VA groups in patients with advanced RP with ultralow vision. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.
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Transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into retinal disease animal models has yielded promising results, and several clinical trials on iPSC-derived retinal pigment epithelial cell transplantation have confirmed its safety. In this study, we performed allogeneic iPSC-derived retinal organoid sheet transplantation in two subjects with advanced retinitis pigmentosa (jRCTa050200027). The primary endpoint was the survival and safety of the transplanted retinal organoid sheets in the first year post-transplantation. The secondary endpoints were the safety of the transplantation procedure and visual function evaluation. The grafts survived in a stable condition for 2 years, and the retinal thickness increased at the transplant site without serious adverse events in both subjects. Changes in visual function were less progressive than those of the untreated eye during the follow-up. Allogeneic iPSC-derived retinal organoid sheet transplantation is a potential therapeutic approach, and the treatment's safety and efficacy for visual function should be investigated further.
Assuntos
Células-Tronco Pluripotentes Induzidas , Retinose Pigmentar , Animais , Humanos , Retina , Retinose Pigmentar/terapia , Visão Ocular , OrganoidesRESUMO
Purpose: To compare the accuracy of intraoperative aberrometry (IA) for predicting postoperative refraction between eyes with emmetropia and myopia targets. Patients and Methods: This retrospective analysis included patients with axial myopia (axial length ≥ 25.0 mm) who underwent uncomplicated phacoemulsification cataract surgery with IA to achieve emmetropia (plano to -0.5 D) or intentional myopia (-2.5 D to -5.0 D). Preoperative ocular biometry was performed in all eyes using an IOLMaster. Refractive prediction errors in IA were compared between eyes with emmetropia and myopia targets. Refractive prediction errors in IA for both groups were also compared with those predicted by intraocular lens power calculation formulas including the SRK/T, Holladay 1, Hoffer Q, Holladay 2, Haigis, and Barrett Universal II formulas. Results: Thirty-nine eyes of 39 patients with a target of emmetropia and 22 eyes of 22 patients with a target of intentional myopia were included in the final analysis. The mean numerical error was significantly different from zero (myopic trend) in myopia-targeted eyes (-0.37 ± 0.54 D, one-sample t-test, P = 0.004, 95% confidence interval: -0.61 to -0.14), while it was close to zero in emmetropia-targeted eyes. The mean absolute error was significantly smaller in emmetropia-targeted eyes (0.28 ± 0.27 D) than in myopia-targeted eyes (0.51 ± 0.41 D, P = 0.01). IA was revealed as the most accurate method for predicting postoperative refraction in eyes with emmetropia target, whereas Barrett Universal II formula was found to be the most accurate for eyes with myopia target. Conclusion: In patients with axial myopia, the performance of IA was altered when targeting intentional myopia compared with emmetropia. Myopic shift in the refractive outcome should be considered when IA is used to target myopia.
RESUMO
This study aimed to evaluate the distribution of retinal pigment epithelium (RPE) melanin in patients with retinitis pigmentosa (RP) using entropy measurements by custom-made polarization-sensitive optical coherence tomography (PS-OCT) images, and compare entropy with the intensity of short-wavelength (SW) and near-infrared (NIR) autofluorescence (AF). We retrospectively reviewed the retinal images, including PS-OCT, SW-AF, and NIR-AF of patients with RP who had a hyperautofluorescent ring on AF. A total of 12 eyes of 12 patients (8 women and 4 men; mean age: 37.9 years) were included. There was a strong positive correlation between entropy value and NIR-AF intensity (r = 0.626, p < 0.001), and there was a very weak negative correlation between entropy value and SW-AF (r = - 0.197, p = 0.001). The mean values of the entropy in the foveal, temporal (2 mm from the fovea), and nasal (2 mm from the fovea) sections were 0.41 (± 0.09), 0.29 (± 0.08), and 0.26 (± 0.08), respectively. The entropy was significantly higher in the foveal section than in the temporal and nasal sections (p = 0.002 and p = 0.003, respectively). There was no significant difference between the entropies values for the temporal and nasal sections (p = 0.157). Age, logMAR best-corrected visual acuity, ellipsoid zone width, and central retinal thickness were not correlated with foveal entropy. We presented RPE melanin imaging in patients with RP using PS-OCT for the first time. PS-OCT can be a useful tool for monitoring patients with RP.