Pathways of neuronal and cognitive development in children born small-for-gestational age or late preterm.

OBJECTIVE: To assess the effects of late small-for-gestational-age (SGA) birth and late prematurity on cognitive outcomes and structural changes in the central nervous system at primary school age, using a novel approach to examine changes in neuronal integrity of the retina. METHODS: We conducted a cross-sectional study of 347 children aged 6-13 years, including in the analysis only infants born after 34 weeks' gestation. We recorded all perinatal outcomes through a survey of parents. Neuronal damage was evaluated using optical coherence tomography of the retina. In a subgroup of 112 children aged 6-8 years, visuospatial perception was evaluated with the Children's Bender Visual Motor Gestalt Test. RESULTS: The proportions of SGA and late preterm children were 11.8 and 6.3%, respectively. Prematurity and SGA were simultaneously present in five children. When compared with controls, SGA children showed significantly lower than average retinal nerve fiber layer (RNFL) thickness (94.1 vs 98.8 µm; P = 0.007) and an increased percentage of abnormal Bender scores (27.3 vs 6.2%; P = 0.017) (odds ratio 5.6 (95% CI, 1.2-26.8)). These differences increased when late SGA infants with a birth weight below the 3(rd) percentile were compared with SGA infants with a birth weight between the 3(rd) and 10(th) percentiles and with controls, for RNFL thickness (92.5 vs 94.6 and 98.8 µm, respectively; P = 0.021) and abnormal Bender tests (33.3 vs 25.0 and 6.2%, respectively; P = 0.036). However, no differences were found in retinal structure and visuomotor performance between late preterm and term infants. CONCLUSIONS: These data suggest that late SGA and late prematurity induce a distinct neuronal pattern of structural changes that persist at school age. Late-onset SGA infants are at increased risk for axonal loss in the retina and present specific visuomotor difficulties.

Three-dimensional geometries representing the retinal nerve fiber layer in multiple sclerosis, optic neuritis, and healthy eyes.

BACKGROUND: To represent and interpret the three-dimensional (3D) geometry and the distribution of the axonal damage to the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS) compared with healthy subjects. To analyze alterations in RNFL morphology in eyes of MS patients with or without previous episodes of optic neuritis (ON). METHODS: MS patients (n = 122) and age-matched healthy subjects (n = 108) were enrolled. The Spectralis optical coherence tomography system was used to determine the circumpapillary RNFL thickness. The 768 RNFL thickness measurements were used to evaluate thickness measurements in patients with or without antecedent ON and to design a 3D reconstruction of the RNFL thickness representing the mechanobiologic tissue response to neurodegeneration caused by MS and ON episodes. RESULTS: RNFL thickness was decreased in MS patients, and was higher in the MS group with previous ON. Statistical analysis and 3D RNFL reconstruction revealed greater damage to the ganglionar cells in the superonasal RNFL area (101.77 µm in MS vs. 125.47 µm in healthy subjects) and in the inferotemporal RNFL (119.05 µm in MS eyes and 149.26 µm in healthy eyes). CONCLUSIONS: The 3D representation of RNFL thickness based on measurements allows physicians to better observe damage in the temporal areas, especially in patients with previous ON.

Analysis of Retinal Layers in Fibromyalgia Patients with Premium Protocol in Optical Tomography Coherence and Quality of Life.

PURPOSE: To evaluate the inner retinal layers in fibromyalgia (FM) patients compared to control subjects using posterior pole protocol (PPole) analysis in optical coherence tomography (OCT) and to correlate structural retinal changes with subjective quality of life. METHODS: Seventy-four eyes of healthy subjects and 55 eyes of those with FM were analyzed. All subjects underwent retinal evaluation using the PPole protocol for Spectralis OCT (Heidelberg Engineering) to obtain measurements of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) in the macular area. The EuroQol (EQ-5D) questionnaire and Fibromyalgia Impact Questionnaire (FIQ) were performed to analyze health-related quality of life. Additionally, the FM group was divided into three groups depending on the disease phenotype (atypical, depressive, and biological). RESULTS: Patients with FM presented with a reduction of the RNFL thickness compared to controls in 17/64 cells of the PPole area, and a reduction of the GCL thickness in 47/64 cells. Depressive FM phenotype showed the greatest number of cells with significant reduction compared with the control group in both RNFL and GCL layers. A correlation between temporal-inferior cells of the GCL and the EuroQol 5D questionnaire results was observed. CONCLUSIONS: Patients with FM present with a reduction of the inner retinal layers in the macular area. This degeneration correlates with disease severity/reduced quality of life in these patients. The PPole protocol for OCT is a non-invasive and fast tool that might help clinicians diagnose and monitor neurodegeneration in FM patients.

Use of the new MultiColour SPECTRALIS® software for identifying retinal nerve fibre layer defects. / Utilidad del nuevo software MultiColor de SPECTRALIS® en la identificación de defectos de la capa de fibras nerviosas de la retina.

The classical fibre photography traditionally used to identify defects in the retinal nerve fibre layer (RNFL), has been partially discontinued due to poor availability. The new MultiColour module of SPECTRALIS® Optical Coherence Tomography (OCT), using three different laser wavelengths simultaneously, can provide images that identify the structures of the retina in different colours according to their depth. A small concordance study was conducted to determine the usefulness of the new MultiColour software versus traditional fibre photography in identifying RNFL defects. The inter-observer agreement in the interpretation of MultiColour images was good (κ=.746; P<.001), as by using Multicolour they were able to identify around 70% of patients with mild glaucoma. It is believed that the new Multicolour software is useful in evaluating RNFL defects, and is easy to perform.

Structure-function relationship in a series of glaucoma cases.

PURPOSE: To map retinal sensitivity and peripapillary retinal nerve fiber layer (RNFL) thickness, as measured by standard automated perimetry (SAP) and optical coherence tomography (OCT) respectively, in patients with various stages of primary open-angle glaucoma (POAG). METHODS: Ninety patients with POAG were prospectively selected for SAP and for OCT RNFL thickness measurements. Factorial analysis performed independently for each hemifield was used to identify groups of related SAP visual field points. Pearson correlation coefficients were determined between visual field regions and peripapillary RNFL sectors and these data used to construct structure-function correlation maps for the various disease stages. RESULTS: Factorial analysis identified 4 factors or visual field regions for the inferior hemifield and 5 for the superior hemifield. For all patients and the subset of patients with advanced POAG, the strongest correlation was detected between the superior hemifield and the inferior RNFL sectors, while higher correlations for incipient and moderate disease stages were observed between the inferior hemifield and the superior RNFL sectors. CONCLUSIONS: In these patients, functional and structural damage can be mapped such that each zone of related SAP points correlates with one or several peripapillary RNFL zones. Such maps could improve our understanding of structure-function relationships in glaucoma.

Ocular manifestations in patient with congenital erythropoietic porphyria.

We present the case of a 52-year-old woman referred to our service because of extreme ocular surface dryness. The patient showed corneal, conjunctival, and eyelid manifestations of ocular congenital erythropoietic porphyria (CEP). We started treatment with autologous serum, topical steroids, and cyclosporine twice a day, topical retinoids, and intense corneal lubrication. The patient referred significant improvement of ocular bothering and less discomfort since treatment was initiated. We describe the management of the herewith presented case of ocular CEP.

Effects of prenatal exposure to alcohol, tobacco and other drugs of abuse on retinal development. / Efectos de la exposición prenatal a alcohol, tabaco y otras drogas de abuso sobre el desarrollo retiniano.

PURPOSE: To assess structural changes in the retina using optical coherence tomography (OCT) in children prenatally exposed to toxic substances. METHODS: The study included a total of 49 infants, aged between 5 and 18years, exposed to toxic substances during pregnancy. Among the exposed children, 25 were exposed to tobacco, 20 were exposed to alcohol, and 4 children were exposed to other drugs of abuse. All children underwent a complete ophthalmology examination, including an OCT. The results were compared against a control group composed of 25 infants, age matched with controlled pregnancy, and not exposed to toxic substances. RESULTS: Children prenatally exposed to toxic substances showed significantly thinner average retinal nerve fibre layer (RNFL) compared with control children (81.5 vs. 99.7µm; P<.005), as well as RNFL thinning in its four quadrants (superior RNFL: 97.5 vs. 127.5µm; P<.005; nasal RNFL: 61.5 vs. 72.3µm; P<.005; inferior RNFL: 99.8 vs. 128.6µm; P<.005, temporal RNFL: 58.3 vs. 68.2µm; P<.005). Exposed children also exhibited a thinner ganglion cell layer (72.9 vs. 85.9; P<.005). Greater RNFL thinning was observed in children exposed to drugs of abuse (RNFL thinner average=72), followed by children exposed to alcohol (RNFL thinner average=72.9), and finally the least affected were those children exposed to tobacco during pregnancy (RNFL=94.6). CONCLUSION: Toxic substances during pregnancy interfere in retinal development. These results strengthen the evidence about the avoidance of any toxic substance during pregnancy.

Functional Evaluation of the Visual Pathway in Patients with Multiple Sclerosis Using a Multifunction Stimulator Monitor.

OBJECTIVES: To assess the capability of the vision monitor unit Monpack One of detecting visual function alterations in patients with multiple sclerosis (MS) and to evaluate the correlation between structural retinal parameters and functional measurements obtained with this device. METHODS: Forty-eight patients with MS and 46 healthy controls were included in a cross-sectional study. All participants underwent a complete functional evaluation of the visual pathway, which included low-contrast visual acuity (LCVA), contrast sensitivity vision (CSV), automated perimetry, multifocal visual evoked potentials (mfVEPs), and pattern electroretinogram (ERG). All tests were performed using the vision monitor unit Monpack One (Metrovision, France), a multifunction stimulator device. Retinal structural measurements were obtained in all subjects using Triton swept source optical coherence tomography (Topcon, Japan). RESULTS: Patients with MS presented reduced low-contrast VA (p < 0.001) and reduced CSV at medium (p=0.001, p=0.013) and low (p=0.001, p=0.002) spatial frequencies. All visual field parameters were found to be altered in MS patients compared with controls (≤0.001). Patients with MS presented lower amplitude of the P100 waveform of the mfVEP in areas corresponding to central (p < 0.001), inferonasal (p=0.001), and inferotemporal (p=0.003) retina. The pattern ERG did not show significant differences. Significant correlations were observed between structural retinal measurements and functional parameters, especially between the inner macular areas and measurements corresponding to contrast sensitivity and perimetry indexes. CONCLUSIONS: Patients with MS present visual dysfunction detectable with the vision monitor unit Monpack One. This device may be a fast and useful tool to provide a full evaluation of axonal damage in patients with multiple sclerosis.

Diagnostic ability of multifocal electroretinogram in early multiple sclerosis using a new signal analysis method.

PURPOSE: To determine if a novel analysis method will increase the diagnostic value of the multifocal electroretinogram (mfERG) in diagnosing early-stage multiple sclerosis (MS). METHODS: We studied the mfERG signals of OD (Oculus Dexter) eyes of fifteen patients diagnosed with early-stage MS (in all cases < 12 months) and without a history of optic neuritis (ON) (F:M = 11:4), and those of six controls (F:M = 3:3). We obtained values of amplitude and latency of N1 and P1 waves, and a method to assess normalized root-mean-square error (FNRMSE) between model signals and mfERG recordings was used. Responses of each eye were analysed at a global level, and by rings, quadrants and hemispheres. AUC (area under the ROC curve) is used as discriminant factor. RESULTS: The standard method of analysis obtains further discrimination between controls and MS in ring R3 (AUC = 0.82), analysing N1 waves amplitudes. In all of the retina analysis regions, FNRMSE value shows a greater discriminating power than the standard method. The highest AUC value (AUC = 0.91) was in the superior temporal quadrant. CONCLUSION: By analysing mfERG recordings and contrasting them with those of healthy controls it is possible to detect early-stage MS in patients without a previous history of ON.

[Diagnostic ability of GDx VCC for glaucoma diagnosis]. / Capacidad diagnóstica del GDx VCC para el diagnóstico del glaucoma.

PURPOSE: To assess the diagnostic ability of scanning laser polarimetry (GDx VCC) to differentiate between normal and glaucomatous eyes. METHODS: 417 eyes of 417 consecutive subjects were prospectively selected. They were classified into 60 healthy controls, 218 ocular hypertensive eyes, 68 glaucoma suspects, and 71 glaucomatous eyes, depending on intraocular pressure, optic nerve head morphology and standard automated perimetry results. All underwent a scanning laser polarimetry with the GDx VCC. Retinal nerve fiber layer (RNFL) parameters of the GDx-VCC were compared among the four groups. Receiver operating characteristic (ROC) curves were plotted between normal and glaucomatous eyes. The best parameters were defined according to the area under the ROC curve and the best sensitivity/specificity balance. RESULTS: Most parameters of GDx-VCC exhibited differences between the glaucoma group and the rest of the groups. Some parameters were also different between healthy patients and glaucoma suspects. The best parameter was the nerve fiber indicator (NFI; area under the ROC curve: 0.876). NFI, superior normalized area, and inferior normalized area yielded the highest sensitivities at 85% and 90% fixed specificity. CONCLUSIONS: Most RNFL parameters measured with the GDx-VCC provided good diagnostic ability for open-angle glaucoma. The best GDx-VCC parameter in differentiating between normal and glaucomatous eyes was the NFI.

Update on visual function and choroidal-retinal thickness alterations in Parkinson's disease. / Actualización sobre alteraciones de función visual y espesores coriorretinianos en la enfermedad de Parkinson.

Parkinson's disease (PD) is a neurodegenerative process that affects 7.5 million people around the world. Since 2004, several studies have demonstrated changes in various retinal layers in PD using optical coherence tomography (OCT). However, there are some discrepancies in the results of those studies. Some of them have correlated retinal thickness with the severity or duration of the disease, demonstrating that OCT measurements may be an innocuous and easy biomarker for PD progression. Other studies have demonstrated visual dysfunctions since early phases of the disease. Lastly, the most recent studies that use Swept Source OCT technology, have found choroidal thickness increase in PD patients and provide new information related to the retinal degenerative process in this disease. The aim of this paper is to review the literature on OCT and PD, in order to determine the altered retinal and choroidal parameters in PD and their possible clinical usefulness, and also the visual dysfunctions with higher impact in these patients.

Correlations between peripapillary retinal nerve fiber layer thickness and macular thickness in different various stages of primary open-angle glaucoma.

PURPOSE: To determine the relationship between macular thickness and peripapillary retinal nerve fiber layer (RNFLp) thickness in different stages of primary open-angle glaucoma (POAG). METHODS: Ninety prospectively selected patients with different stage POAG underwent spectral domain optical coherence tomography (SD-OCT) to determine macular and RNFLp thicknesses in different regions and sectors respectively. Correlations were then established through Pearson's correlation coefficient between RNFLp and macular thicknesses in the different disease stages. RESULTS: Greatest correlation was observed between the inferior RNFLp sector and the internal inferior macula both in the whole patient population and in the subset of patients with incipient glaucoma. CONCLUSIONS: When the optic nerve disc is affected by another condition, macular thickness determination may help detect POAG and monitor its progression.

Visual dysfunction and its correlation with retinal changes in patients with Alzheimer's disease.

AimTo evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Alzheimer's disease (AD).MethodsPatients with AD (n=24) and controls (n=24) underwent evaluation of visual acuity (VA), color vision (using the Farnsworth and L'Anthony desaturated (D) 15 color tests), and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV-1000E test) to measure visual dysfunction. Structural measurements of the retinal nerve fiber layer (RNFL) and macular thickness were obtained using spectral domain-optical coherence tomography (SD-OCT).ResultsCSV at three of the four spatial frequencies was significantly worse in AD patients than in controls. Color vision was significantly affected in AD patients based on the Farnsworth color test. Compared with controls, macular thinning was detected in all sectors except the fovea, and the RNFL exhibited significant thinning in the superior quadrant and lower average thickness (P<0.05). CSV was the functional parameter most strongly correlated with structural measurements in patients with AD. Color vision was strongly associated with macular volume (r>0.70, P<0.05). VA at different levels of contrast was associated with macular and RNFL thickness.ConclusionsPatients with AD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. Macular measurements may be reliable indicators of visual impairment in AD patients.

Contact topical anesthesia versus general anaesthesia in strabismus surgery.

OBJECTIVE: To evaluate the anesthetic block provided by contact topical anesthesia (CTA) in strabismus surgery in adult patients. To analyze postoperative pain and surgical outcome obtained by CTA compared with general anesthesia (GA). METHODOLOGY: Prospective longitudinal cohort study of adult patients undergoing strabismus surgery by CTA or GA. The intensity of pain perceived by patients during the course of surgery and in the postoperative period was measured using Numerical Pain Scale. The success of the surgical outcome, considered as a residual ocular deviation<10 prism diopters, was evaluated. RESULTS: Twenty-three patients were operated using CTA and 26 using AG. During the course of surgery, pain intensity experienced by patients in ATC group was 3.17±2.44. There were no differences between CTA group and AG group in the intensity of pain in the immediate postoperative period (2.13±2.39 vs. 2.77±2.18, respectively; P=.510) and during the first postoperative day (3.22±2.84 vs. 3.17±2.73; P=.923). Surgical success was significantly higher in the CTA group than in the GA group (78.3 vs. 73.1%; P=.019). CONCLUSIONS: CTA provides adequate sensory block to perform strabismus surgery. The control of postoperative pain is similar to that obtained with AG. Conservation of ocular motility providing CTA enables better surgical outcome.

Visual dysfunction and its correlation with retinal changes in patients with Parkinson's disease: an observational cross-sectional study.

OBJECTIVES: To evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinson's disease (PD). METHODS: Patients with PD (n=37) and controls (n=37) were included in an observational cross-sectional study, and underwent visual acuity (VA), colour vision (using the Farnsworth and Lanthony desaturated D15 colour tests) and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fibre layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses, were obtained using spectral domain optical coherence tomography (SD-OCT). Comparison of obtained data, and correlation analysis between functional and structural results were performed. RESULTS: VA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in patients with PD than in controls. Colour vision was significantly affected based on the Lanthony colour test. Significant GCL loss was observed in the minimum GCL+inner plexiform layer. A clear tendency towards a reduction in several macular sectors (central, outer inferior, outer temporal and superior (inner and outer)) and in the temporal quadrant of the RNFL thickness was observed, although the difference was not significant. CSV was the functional parameter most strongly correlated with structural measurements in PD. Colour vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r>0.70, p<0.05). CONCLUSIONS: Patients with PD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. GCL measurements may be reliable indicators of visual impairment in patients with PD.

Study of perfusion changes in the optic disc of patients with fibromyalgia syndrome using new colorimetric analysis software.

PURPOSE: We measured the amount of hemoglobin at the optic nerve head of fibromyalgia (FM) patients using new colorimetric analysis software. We also investigated whether perfusion defects of the optic nerve head in patients with FM lead to tissue atrophy and corresponding retinal nerve fiber layer (RNFL) thinning measured by optical coherence tomography (OCT). METHODS: We recruited for this cross-sectional study 118 FM patients and 76 sex- and age-matched healthy controls. All subjects underwent a complete neuro-ophthalmologic examination, which also included visual field testing using the Spark strategy in an Easyfield perimeter, and OCT examinations using the Spectralis. One photograph of the optic disc was obtained using a Cirrus™ Photo 800 multi-modality imager. We analyzed fundus photographs using Laguna ONhE software, a new method that allows hemoglobin levels to be measured at the optic nerve head. We compared hemoglobin percentages in different sectors of the nerve head and RNFL thicknesses between the two groups. RESULTS: Mean hemoglobin percentages and hemoglobin content in all optic nerve head sectors calculated by the Laguna ONhE program were significantly lower in FM patients than in healthy controls, and the main differences were detected in the outer ring, which corresponds with the neuroretinal rim. However, only the differences in the superotemporal RNFL were statistically significant. Correlations between the RNFL thickness and the percentage of hemoglobin in the different sectors were weak. CONCLUSION: Optic disc perfusion was decreased in patients with FM, especially within the neuroretinal rim, without clear involvement in the RNFL.

Guidelines for treatment of chronic primary angle-closure glaucoma.

OBJECTIVE: To present a clinical practice guideline update on the medical, laser, and surgical treatment of primary angle closure glaucoma (PACG) in adults. METHODS: Following the formulation of key questions using the PICO scheme (Patient/Problem, Intervention, Comparison, Outcome), a systematic review was performed on the literature published to date, including international clinical practice guidelines. The AMSTAR and Risk of Bias tools were used for evaluating the quality of the information. The level of evidence and grade of recommendation was established following the Scottish Intercollegiate Guidelines Network (SIGN) system. RESULTS: Following the above methodology, recommendations of medical, laser and surgical treatment in adult PACG and levels of evidence are presented. CONCLUSIONS: Although the level of scientific evidence for many of the questions raised is not very high, a review is presented on updated treatment recommendations for adult PACG. Among the limitations for the implementation of these recommendations is that most studies have been conducted in Asian populations, and that the effectiveness is measured almost exclusively in terms of reducing intraocular pressure, and does not include visual function, quality of life or cost-effectiveness parameters.

Short-wavelength automated perimetry and retinal nerve fiber layer evaluation in suspected cases of glaucoma.

OBJECTIVES: To determine if short-wavelength automated perimetry (SWAP) provides evidence that indicates early functional losses in ocular hypertensive subjects and to establish a direct comparison with early structural abnormalities in the retinal nerve fiber layer (RNFL). METHODS: A total of 160 eyes belonging to 83 patients with ocular hypertension (intraocular pressure >21 mm Hg and normal results on standard automated perimetry evaluation), on which a SWAP and RNFL study were performed, were examined. One hundred twenty-eight age-matched subjects without ocular hypertension were evaluated to establish the 95% and 99% confidence intervals at each of the 76 exploration points of the SWAP test. RESULTS: The RNFL study results were normal in 83 cases (51.8%) and pathologic in 77 cases (48.1%). The SWAP results were pathologic in 57 cases (35.6%). Significant differences (P<.001) were observed when comparing the distribution of normal and pathologic SWAP results among the types of defects in the RNFL (focal wedge, diffuse atrophy, and mixed atrophy). CONCLUSIONS: Short-wavelength automated perimetry is a useful test for the early detection of visual field losses. It is more sensitive than standard automated perimetry and provides a high association with RNFL assessment, which has proved capable of detecting signs of glaucomatous damage several years before the onset of the typical visual field defects.

Correlation of functional and structural measurements in eyes suspected of having glaucoma.

PURPOSE: This study was conducted to determine the correlation between structural changes in the retinal nerve fiber layer (RNFL) and functional loss detected on short-wavelength automated perimetry (SWAP) in a population of patients with suspected glaucoma. METHODS: With a selection criteria of intraocular pressure (IOP) more than 21 mmHg and normal results of conventional automated perimetry, 49 eyes of 49 patients with ocular hypertension were enrolled in the study. The SWAP was performed with a modified Humphrey field analyzer, and visual field indexes (mean deviation [MD], corrected pattern standard deviation [CPSD]) were calculated. Semiquantitative RNFL scores were given separately to diffuse and localized defects of the RNFL. RESULTS: The MD increased significantly with higher diffuse and total RNFL scores, with good correlation coefficients. A weak correlation was found between CPSD and diffuse, total, and localized RNFL scores. CONCLUSION: Diffuse RNFL loss are associated with abnormalities in visual field indexes (MD), whereas focal structural damage showed no correlation with visual field loss.