Correlation Between Ophthalmologic and Neuroradiologic Findings in Type 1 Neurofibromatosis.

BACKGROUND: Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings. METHODS: This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established. RESULTS: Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings. CONCLUSIONS: This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients.

Cone dystrophy with supernormal rod responses: A rare KCNV2 gene variant.

PURPOSE: To describe the clinical, electrophysiological, and genetic findings of three Portuguese families with a rare variant in the KCNV2 gene resulting in "cone dystrophy with supernormal rod responses" (CDSRR). METHODS: Retrospective clinical revision of five individuals from three unrelated families with CDSRR. Ophthalmological examination was described in all patients and included color vision testing, fundus photography, fundus autofluorescence (FAF) imaging, spectral domain-optical coherence tomography (SD-OCT), pattern electroretinogram (ERG), and full-field ERG. The mutational screening of the KCNV2 gene was performed with Sanger and Next Generation Sequencing. RESULTS: All patients showed childhood-onset photophobia and progressive visual acuity loss with varying degrees of severity. In multimodal imaging, various degrees of retinal pigment epithelium disturbances and outer retinal atrophy, which tend to be worst with advancing age, were observed. Molecular screening identified a rare presumed truncating variant (p.Glu209Ter) in homozygosity in two families and in compound heterozygosity in a third family. Three patients showed ERG changes characteristic of CDSRR, however, two patients presented with incomplete electrophysiological features of the disease. CONCLUSION: A rare variant in the KCNV2 gene was identified in five patients from three Portuguese families. This variant often leads to a severe and progressive form of retinopathy. Considerable variability in the ERG responses among patients with this KCNV2 variant was observed.

Corneal structure and endothelial morphological changes after uneventful phacoemulsification in type 2 diabetic and nondiabetic patients / Alterações da estrutura e endotélio da cornea após facoemulsificação sem complicações em pacientes diabéticos tipo 2 e não diabéticos

ABSTRACT Purpose: The aim of this study was to compare corneal structure and endothelial morphological changes after uneventful phacoemulsification cataract surgery between type 2 diabetic and nondiabetic patients and to determine the preoperative and intraoperative factors that may predict greater endothelial cell density loss. Methods: Forty-five diabetic pa­tients (45 eyes) and 43 controls (43 eyes) with age-related cataract were enrolled in this prospective observational study. Corneal (thickness and volume) and anterior segment parameters were measured by Scheimpflug tomography; endothelial cell density and morphology (coefficient of variation of cell size, hexagonal cells) were recorded using noncontact specular microscopy. Patients were evaluated preoperatively and at one and six months after surgery. Univariate and multivariate linear regression analyses were performed to evaluate the relationship between demographic, clinical, ocular, and intraoperative parameters and postoperative endothelial cell density changes at six months. Results: Significant postoperative endothelial cell loss occurred one month after surgery in both groups (p<0.001), which remained stable until month 6; there were no differences between patients with and without diabetes mellitus at any time point. The mean postoperative central corneal thickness at one and six months did not change significantly from the mean preoperative value in either group (p>0.05). Multivariate linear regression analysis showed that older age (p=0.042) and higher cataract grades (p=0.001) were significantly associated with greater endothelial cell density reduction at six-month follow-up. Conclusion: This study showed that older age and denser cataracts might be associated with greater endothelial cell density reduction after cataract surgery. Other factors, such as diabetes mellitus and preoperative anterior segment parameters, did not influence postoperative changes in endothelial cell density.

RESUMO Objetivo: Comparar a estrutura da córnea e as alterações mor­fológicas endoteliais após cirurgia de catarata por facoemulsificação sem intercorrências entre pacientes com diabetes mellitus tipo 2 e não diabéticos; e determinar quais fatores pré e intra-operatórios relacionados com a maior redução da densidade celular endotelial. Métodos: Quarenta e cinco diabéticos (45 olhos) e 43 (43 olhos) controlos com catarata relacionada à idade foram incluídos neste estudo observacional prospectivo. Os parâmetros da córnea (espessura e volume) e do segmento anterior foram medidos pela tomografia Scheimpflug; a densidade e morfologia celular endotelial (coeficiente de variação do tamanho das células, células hexagonais) foram registrados usando microscopia especular não contato. Os pacientes foram avaliados no pré-operatório, 1 e 6 meses após a cirurgia. Foi realizada uma análise de regressão linear uni e multivariada para avaliar a relação entre os parâmetros demográficos, clínicos, oculares e intra-operatórios com a redução da densidade celular endotelial aos 6 meses. Resultados: Nos dois grupos houve uma perda significativa de células endoteliais ao 1º mês pós-ope­ratório (p<0,001), que permaneceu estável até ao 6º mês; sem diferenças estatisticas entre os grupos diabetes mellitus e não diabetes mellitus em qualquer avaliação. A espessura média da córnea no pós-operatório central aos 1 e 6 meses não mudou significativamente em relação ao valor médio pré-operatório nos dois grupos (p>0.05). A análise de regressão multivariada linear mostrou que a idade avançada (p=0.042) e os graus mais elevados de catarata (p=0.001) foram significativamente associados à maior redução densidade celular endotelial aos 6 meses de seguimento. Conclusão: Este estudo mostrou que a idade avançada e as cataratas mais densas podem predispor a uma maior redução densidade celular endotelial após a cirurgia de catarata. Outros fatores, como diabetes mellitus e parâmetros pré-operatórios do segmento anterior, não influenciaram significativamente as alterações pós-operatórias da densidade celular endotelial.

Corneal structure and endothelial morphological changes after uneventful phacoemulsification in type 2 diabetic and nondiabetic patients.

PURPOSE: The aim of this study was to compare corneal structure and endothelial morphological changes after uneventful phacoemulsification cataract surgery between type 2 diabetic and nondiabetic patients and to determine the preoperative and intraoperative factors that may predict greater endothelial cell density loss. METHODS: Forty-five diabetic pa-tients (45 eyes) and 43 controls (43 eyes) with age-related cataract were enrolled in this prospective observational study. Corneal (thickness and volume) and anterior segment parameters were measured by Scheimpflug tomography; endothelial cell density and morphology (coefficient of variation of cell size, hexagonal cells) were recorded using noncontact specular microscopy. Patients were evaluated preoperatively and at one and six months after surgery. Univariate and multivariate linear regression analyses were performed to evaluate the relationship between demographic, clinical, ocular, and intraoperative parameters and postoperative endothelial cell density changes at six months. RESULTS: Significant postoperative endothelial cell loss occurred one month after surgery in both groups (p<0.001), which remained stable until month 6; there were no differences between patients with and without diabetes mellitus at any time point. The mean postoperative central corneal thickness at one and six months did not change significantly from the mean preoperative value in either group (p>0.05). Multivariate linear regression analysis showed that older age (p=0.042) and higher cataract grades (p=0.001) were significantly associated with greater endothelial cell density reduction at six-month follow-up. CONCLUSION: This study showed that older age and denser cataracts might be associated with greater endothelial cell density reduction after cataract surgery. Other factors, such as diabetes mellitus and preoperative anterior segment parameters, did not influence postoperative changes in endothelial cell density.

Evaluation of Corneal Structure and Endothelial Morphological Characteristics in Type 2 Diabetic and Non-Diabetic Patients.

PURPOSE: To compare corneal structure and endothelial morphological features between patients with type 2 diabetes mellitus (DM) and non-diabetic patients; and determine if the DM duration, glycated hemoglobin (HbA1c) levels, and diabetic retinopathy (DR) stage affect corneal morphological properties. PATIENTS AND METHODS: Sixty diabetic patients and 47 age- and sex-matched controls were enrolled in this cross-sectional study. DM group was analyzed according disease duration, HbA1c levels, and presence of retinopathy. Endothelial cell density (ECD) and morphology (average and coefficient of variation [CV] of cell size, percentage of hexagonal cells) were recorded using non-contact specular microscopy. Central corneal thickness (CCT) and corneal volume were measured by scheimpflug tomography. Univariate and multivariate linear regression analyses were performed to evaluate the relationship between demographical, clinical, and ocular variables with CCT and ECD. RESULTS: There were no statistically significant differences in the endothelium cell density or morphology between DM and non-DM groups (p>0.05). Also, there was no statistical difference between groups for CCT or corneal volume (p>0.05). Multivariate linear regression analysis showed that older age (p=0.028) was significantly associated with lower ECD; CCT was found to be significantly greater in males (p<0.001) and positively associated with corneal volume (p<0.001). CONCLUSION: The present study did not find any statistically significant differences between the corneal structural and endothelial characteristics of diabetic and non-diabetic subjects; other demographical parameters, such as age and gender, seem to be more determinant for the corneal properties.

Agreement between IOLMaster® 500 and Pentacam® HR for keratometry assessment in type 2 diabetic and non-diabetic patients.

AIM: To evaluate inter-device agreement of anterior keratometry obtained by the IOLMaster® 500 and Pentacam® HR in type 2 diabetic and non-diabetic patients. METHODS: Corneal measurements were sequentially performed in 60 diabetes mellitus (DM) and 48 age and sex-matched controls undergoing cataract surgery. Variables recorded included flat and steep keratometry, mean keratometry (Km), astigmatism magnitude, axis location, J0 and J45 components. Bland-Altman plots and intraclass correlation coefficients were used for examination of agreement. Subgroup analyses were performed for astigmatism magnitude, diabetes duration, hemoglobin A1c (HbA1c) levels and diabetic retinopathy (DR) stage. RESULTS: Agreement for Km and astigmatism magnitude were considered good and moderate, with 95% limits of agreement (LoA) of -1.09 to 1.23 diopters (D) and -0.83 to 0.86 D in DM group, respectively; and -0.59 to 0.72 D and -0.98 to 0.75 D in non-DM group, respectively. In contrast, the 95% LoA for corneal axis exceeded the clinically relevant margins in both groups. In the total sample, only 41 eyes (38%) had a smaller than 5-degree difference. Diabetes duration, HbA1c levels and DR stage were not found to significantly affect agreement. Logistic regression showed that higher corneal power (P=0.021) and astigmatism magnitude (P=0.011) were associated with a decreased risk of having a difference in axis location greater than 10-degrees. CONCLUSION: In both groups, IOLMaster and Pentacam agree well for corneal power and moderately for astigmatism. However, axis location disagreement is frequent in eyes with flatter corneas and small amounts of astigmatism.

Corneal Biomechanical Changes After Uneventful Phacoemulsification in Patients With Type 2 Diabetes Mellitus and Patients Without Diabetes.

PURPOSE: To compare corneal biomechanical changes after uneventful phacoemulsification cataract surgery between type 2 diabetic (DM) and nondiabetic patients. METHODS: Forty-four diabetic (44 eyes) and 44 (44 eyes) age and sex-matched non-DM controls with age-related cataract were enrolled in this prospective observational study. Corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated intraocular pressure (IOPcc) were evaluated by using the ocular response analyzer; central corneal thickness was recorded by using the Pentacam HR. Patients were evaluated preoperatively and 1 and 6 months after surgery. RESULTS: In the DM group, CH was observed to be significantly lower than preoperative value (9.8 ± 1.5 mm Hg) at 1 month (9.4 ± 1.2 mm Hg, P = 0.040), but not at the 6-month follow-up (9.6 ± 1.6 mm Hg, P = 0.437),whereas it did not change significantly in the non-DM group (preoperative 9.8 ± 1.3 mm Hg vs. 1 month 9.6 ± 1.1 mm Hg vs. 6 months 10.1 ± 1.1 mm Hg, P > 0.05). CRF was significantly lower than the preoperative values at 1 and 6 months in both groups (P ≤ 0.001). Postoperative CH change was significantly associated with preoperative CH (P < 0.001), preoperative IOPcc (P = 0.004), and IOPcc change (P < 0.001), whereas CRF change was only correlated with preoperative CRF (P < 0.001). There was a significant postoperative IOPcc reduction 6 months after surgery (P < 0.001) in both DM and non-DM groups; however, central corneal thickness was not found to significantly change in the postoperative period (P > 0.05). CONCLUSIONS: This study showed that phacoemulsification causes a significant and persistent decrease in intraocular pressure and CRF in both groups, whereas CH recovered to preoperative values, although more slowly in patients with diabetes.

Clinical Characteristics of the Charles Bonnet Syndrome in Patients with Neovascular Age-Related Macular Degeneration: The Importance of Early Detection.

PURPOSE: We investigated the characteristics, prognosis, and clinical outcome of the Charles Bonnet syndrome (CBS) in patients with neovascular age-related macular degeneration (AMD). METHODS: Five hundred psychiatrically healthy patients with neovascular AMD were screened for CBS. The individuals that fulfilled the inclusion criteria were systematically interviewed using a structured questionnaire that covered the impact, prognosis, risk factors, phenomenology, symptoms, and knowledge about the syndrome. A control group of 45 patients was used for comparison. Demographic data, current medication, and ocular risk factors were collected in all patients. RESULTS: Forty-five patients with CBS were identified. The majority of patients reported images that consisted of colored (62%) animals (44%) or faces (42%) that lasted for seconds (53%). Most patients reported a self-limited disease with a median duration of symptoms between 9 and 11.5 months, with only 7% knowing about CBS at symptom onset. The degree of visual deficit did not predict the characteristics, complexity, frequency, duration, or impact of visual hallucinations. One-third of patients reported negative outcome, which was associated with shorter duration of CBS (p = 0.023), fear-inducing images (p < 0.001), and impact on daily activities (p = 0.015). CONCLUSION: The prevalence of CBS in neovascular AMD patients is high and clinically relevant. Patients with recent onset of visual hallucinations and describing fear-inducing images are at greater risk for negative outcome. Periodic screening may minimize the negative consequences of this disease.

Adequacy of the Fogging Test in the Detection of Clinically Significant Hyperopia in School-Aged Children.

PURPOSE: To evaluate the efficacy of the "fogging test," performed with a +2 diopters (D) lens, in the exclusion of clinically significant hyperopia in school-aged children. METHODS: We studied 54 children between 5 and 11 years of age, with 10/10 best-corrected bilateral visual acuity (VA) without significant degree of correction. VA was assessed in each eye with a "bilateral" +2 D sphere over-refraction followed by cycloplegic retinoscopy. The capacity of the test to detect hyperopia of ≥+2 D and ≥+1.5 D was evaluated by examining the respective receiver operating characteristic (ROC) curves and sensitivity and specificity values for different cutoff values of VA. RESULTS: For the detection of hyperopia ≥+2 D, the area under the ROC curve (AUC) was 0.955 (p ≤ 0.001). The VA cutoff with best discriminative capacity was ≥5/10, with a sensitivity of 100%, specificity of 79%, positive predictive value (PPV) of 57%, and negative predictive value (NPV) of 100%. In respect of ≥+1.5 D hyperopia, the test capacity was lower (AUC = 0.832; p ≤ 0.001). The best VA cutoff was also of ≥5/10, with a PPV of 81% and a NPV of 85%. CONCLUSION: The accuracy of the test was high for the evaluation of ≥+2 D hyperopia but lower for ≥+1.5 D hyperopia. For the detection of ≥+2 D hyperopia, the VA cutoff of <5/10 may permit the exclusion of clinically significant hyperopia in selected children, without the need for cycloplegia. For the same cutoff, the PPV was low, meaning that in children with ≥5/10 VA cycloplegic refraction remains obligatory.

Intraocular Pressure and Anterior Segment Morphometry Changes after Uneventful Phacoemulsification in Type 2 Diabetic and Nondiabetic Patients.

PURPOSE: To compare intraocular pressure (IOP) and anterior segment (AS) morphometry changes after uneventful phacoemulsification between nonglaucomatous eyes with open-angles from patients with and without type 2 diabetes mellitus (DM) and determine which factors may predict greater IOP-lowering effect. METHODS: Forty-five diabetic (45 eyes) and 44 (44 eyes) age- and sex-matched non-DM patients with age-related cataract were enrolled in this prospective observational study. Goldmann applanation tonometry and AS Scheimpflug tomography (Pentacam® HR) were performed preoperatively and at 1- and 6-month follow-up. Linear regression analysis was performed to evaluate the clinical variables related to postoperative IOP changes at 6 months. RESULTS: There was a significant postoperative IOP reduction 6 months after surgery (p < 0.001) by an average of 2.9 ± 2.9 mmHg (15.5%) and 2.4 ± 2.8 mmHg (13.0%) in the DM group and non-DM groups (p = 0.410), respectively. All AS parameters (anterior chamber depth, volume, and angle) increased significantly postoperatively (p < 0.001). Multivariate linear regression analysis showed that higher preoperative IOP was significantly associated with IOP reduction at 6-month follow-up (p < 0.05). CONCLUSION: Nonglaucomatous eyes with open-angles from both type 2 diabetic and nondiabetic patients experienced similar AS changes and IOP reductions following uneventful phacoemulsification, and this IOP-lowering effect was strongly correlated with preoperative IOP.

Structural and Biomechanical Corneal Differences between Type 2 Diabetic and Nondiabetic Patients.

PURPOSE: To analyze and compare corneal structural and biomechanical properties, characterized by corneal hysteresis (CH) and resistance factor (CRF), between patients with and without type 2 diabetes mellitus (DM), and determine the main ocular variables that influence them. METHODS: Sixty diabetic and 48 age- and sex-matched non-DM patients were enrolled in this cross-sectional study. The DM group was analyzed according to DM duration (