Early Stages Of Retinitis Pigmentosa Research Articles

Adaptive optics retinal imaging in patients with usher syndrome

PurposeTo determine the structure of the cone photoreceptor mosaic in the macula in eyes with retinitis pigmentosa related to Usher syndrome using adaptive optics fundus (AO) imaging and to correlate these findings with those of the standard clinical diagnostics.MethodsTen patients with a genetically confirmed retinitis pigmentosa in Usher syndrome due to biallelic variants in MYO7A or USH2A were enrolled in the study. All patients underwent a complete ophthalmological examination including best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT) with fundus autofluorescence photography (FAF), full-field (ffERG) and multifocal electroretinography (mfERG) and Adaptive Optics Flood Illuminated Ophthalmoscopy (AO, rtx1™, Imagine Eyes, Orsay, France). The cone density was assessed centrally and at each 0.5 degree horizontally and vertically from 1–4 degree of eccentricity.ResultsIn the AO images, photoreceptor cell death was visualized as a disruption of the cone mosaic and low cone density. In the early stage of the disease, cones were still visible in the fovea, whereas outside the fovea a loss of cones was recognizable by blurry, dark patches. The blurry patches corresponded to the parafoveal hypofluorescent ring in the FAF images and the beginning loss of the IS/OS line and external limiting membrane in the SD-OCT images. FfERGs were non-recordable in 7 patients and reduced in 3. The mfERG was reduced in all patients and correlated significantly (p <0.001) with the cone density. The kinetic visual field area, measured with III4e and I4e, did not correlate with the cone density.ConclusionThe structure of the photoreceptors in Usher syndrome patients were detectable by AO fundus imaging. The approach of using high-resolution technique to assess the photoreceptor structure complements the established clinical examinations and allows a more sensitive monitoring of early stages of retinitis pigmentosa in Usher syndrome.

Spatial Transcriptomic Analysis Reveals Regional Transcript Changes in Early and Late Stages of rd1 Model Mice with Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is the leading cause of inherited blindness with a genetically heterogeneous disorder. Currently, there is no effective treatment that can protect vision for those with RP. In recent decades, the rd1 mouse has been used to study the pathological mechanisms of RP. Molecular biological studies using rd1 mice have clarified the mechanism of the apoptosis of photoreceptor cells in the early stage of RP. However, the pathological changes in RP over time remain unclear. The unknown pathology mechanism of RP over time and the difficulty of clinical treatment make it urgent to perform more refined and spatially informed molecular biology studies of RP. In this study, spatial transcriptomic analysis is used to study the changes in different retinal layers of rd1 mice at different ages. The results demonstrate the pattern of photoreceptor apoptosis between rd1 mice and the control group. Not only was oxidative stress enhanced in the late stage of RP, but it was accompanied by an up-regulation of the VEGF pathway. Analysis of temporal kinetic trends has further identified patterns of changes in the key pathways of the early and late stages, to help understand the important pathogenesis of RP. Overall, the application of spatial transcriptomics to rd1 mice can help to elucidate the important pathogenesis of RP involving photoreceptor apoptosis and retinal remodeling.

ASSESSMENTS OF MACULAR FUNCTION BY FOCAL MACULAR ELECTRORETINOGRAPHY AND STATIC PERIMETRY IN EYES WITH RETINITIS PIGMENTOSA.

To assess the macular function by focal macular electroretinography and static perimetry in eyes with retinitis pigmentosa. Eighty-eight eyes of 88 retinitis pigmentosa patients were analyzed. The relationships between the focal macular electroretinography components and the mean deviations (MDs) of the Humphrey Field Analyzer 10-2 were determined. Spectral-domain optical coherence tomography was used to determine the integrity of the ellipsoid zone (EZ) and the interdigitation zone. Forward-backward stepwise regression analyses showed that the amplitudes (r = 0.45, P < 0.01) and implicit times (r = -0.29, P < 0.01) of the b-waves were significantly correlated with the MDs. Some of the eyes had reduced b-wave amplitudes (<1.0 µ V) and disrupted interdigitation zone, despite having a better MD (≥ -10.0 dB) and intact EZ. Subgroup analyses of eyes with better MD (≥ -10.0 dB) showed that the EZ width was correlated with the MDs but not with the b-wave amplitude. The thickness of the EZ-retinal pigment epithelium as an alternative indicator of interdigitation zone was correlated with the b-wave amplitude (r = 0.32, P = 0.04) but not with the MDs (r = -0.10, P = 0.53). The fact that the focal macular electroretinography amplitudes are reduced before the shortening of the EZ in the early stage of retinitis pigmentosa indicates that the focal macular electroretinography amplitudes are an earlier indicator of macular dysfunction than the Humphrey Field Analyzer 10-2 findings.

Topical Ocular Administration of Progesterone Decreases Photoreceptor Cell Death in Retinal Degeneration Slow (rds) Mice.

Retinitis pigmentosa (RP) is an inherited eye disorder which triggers a cascade of retinal disorders leading to photoreceptor cell death and for which there is currently no effective treatment. The purpose of this research was to study whether ocular administration of a solution of progesterone (PG) in β-cyclodextrins (CD) could delay photoreceptor cell death and counteract the gliosis process in an animal model of RP (rds mice). The possible effect of PG reaching the contralateral eye through the circulatory system was also evaluated. Finally, this research discusses and evaluates the diffusion of the drug from possible topical formulations for ocular administration of PG. A group of rds mice received one drop of a solution of PG in CD every 12 h for 10 days to the left eye, while the right eye was left untreated. Another group of rds mice (control) received the drug vehicle (PBS) on the left eye and, again, the right eye was left untreated. Once the treatment was finished on postnatal day 21, the animals were euthanized and histological immunofluorescence studies (TUNEL, GFAP, and DAPI staining) were carried out. Our results showed that the administration of a solution of PG in CD (CD-PG) as drops significantly decreased cell death and inflammation in the retina of the PG-treated eyes of rds mice. No effect was seen in the contralateral eye from PG that may have entered systemic circulation. In conclusion, CD-PG applied topically as drops to the eye decreases photoreceptor cell death in the early stages of RP, delaying vision loss and decreasing gliosis.

Outcomes of transcorneal electrical stimulation therapy in the early stages of retinitis pigmentosa.

To investigate the effect of transcorneal electrical stimulation (TES) therapy in patients with retinitis pigmentosa (RP). We performed TES therapy in 21 patients with RP in 12 sessions with 1-week intervals. The following parameters obtained before and after the TES therapy were compared statistically; the best corrected visual acuity (BCVA, logMAR), Ishihara color vision level, multifocal electroretinography (mf-ERG) response, automated visual field (VF) outcome, and the 25-item low vision quality-of-life (LVQOL) questionnaire points. The mean age of patients (6 females; 15 males) was 31.67 ± 9.80 years (20-50 years). While increases in BCVA level, color vision level, mf-ERG response in p1 amplitude of ring 1, and LVQOL questionnaire points were statistically significant, changes in VF test and other mf-ERG responses were not. Twenty of the patients (95.24%) stated that they were satisfied with the TES therapy. No considerable side effect was observed in any patient due to the therapy. The TES therapy may be an effective and safe treatment modality in slowing the RP progression, especially in the early stages of the disease. Longer-term follow-ups in larger patient populations are warranted.

Multifocal electroretinography in assessment of the functional state of the central retina in patients with retinitis pigmentosa

To evaluate the information content of multifocal electroretinography (mfERG) in the diagnostics of the functional state of the central retina in retinitis pigmentosa (RP). The study included 115 patients (228 eyes) with PR and 15 people (30 eyes) who comprised the control group. All subjects underwent standard ophthalmological examination, computer perimetry, color vision study, retinal spectral optical coherence tomography, ganzfeld electroretinography (gERG) and mfERG. The relationship between mfERG parameters and the degree of gERG changes, as well as various functional and morphological parameters of the retina was assessed. Visual acuity and perimetry indices varied over a wide range. GERG was unrecordable in 50.4% of cases. MfERG was registered in 214 (98.3%) eyes with varying degrees of change in visual acuity, visual field and gERG parameters. A medium degree positive relationship was revealed between the biopotential density of the retina in the foveal and parafoveal zones and visual acuity (rs=0.68; 0.63), a high degree - between the density of ttotal biopotential of the central retina (DValue) and the average light sensitivity (rs=0.9), a weak degree - between DValue and the thickness and volume of the peripheral retina (rs=0.37; 0.42), a medium negative correlation was found between the average defect in light sensitivity and the biopotential density in the periphery (Rings 4-5) on mfERG, DValue (rs= -0.67; -0.65; -0.69). MfERG detects retinal dysfunctions at an early stage of RP, in eyes with high visual acuity, normal parameters of the central visual field and gERG, as well as in low visual acuity, a pronounced decrease in light sensitivity, unrecordable gERG. MfERG can be informative in the selection of patients with RP for gene therapy.

Visual Cortex Engagement in Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a family of inherited disorders caused by the progressive degeneration of retinal photoreceptors. There is no cure for RP, but recent research advances have provided promising results from many clinical trials. All these therapeutic strategies are focused on preserving existing photoreceptors or substituting light-responsive elements. Vision recovery, however, strongly relies on the anatomical and functional integrity of the visual system beyond photoreceptors. Although the retinal structure and optic pathway are substantially preserved at least in early stages of RP, studies describing the visual cortex status are missing. Using a well-established mouse model of RP, we analyzed the response of visual cortical circuits to the progressive degeneration of photoreceptors. We demonstrated that the visual cortex goes through a transient and previously undescribed alteration in the local excitation/inhibition balance, with a net shift towards increased intracortical inhibition leading to improved filtering and decoding of corrupted visual inputs. These results suggest a compensatory action of the visual cortex that increases the range of residual visual sensitivity in RP.

Nutraceutical Supplementation Ameliorates Visual Function, Retinal Degeneration, and Redox Status in rd10 Mice.

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive degeneration of photoreceptor cells. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In this study, we investigated the effect of a mixture of nutraceuticals with antioxidant properties (NUT) on retinal degeneration in rd10 mice, a model of RP. NUT was orally administered to rd10 mice from postnatal day (PD) 9 to PD18. At PD18 retinal function and morphology were examined by electroretinography (ERG) and histology including TUNEL assay, immunolabeling of microglia, Müller cells, and poly ADP ribose polymers. Retinal redox status was determined by measuring the activity of antioxidant enzymes and some oxidative stress markers. Gene expression of the cytokines IL-6, TNFα, and IL-1β was assessed by real-time PCR. NUT treatment delayed the loss of photoreceptors in rd10 mice partially preserving their electrical responses to light stimuli. Moreover, it ameliorated redox status and reduced inflammation including microglia activation, upregulation of cytokines, reactive gliosis, and PARP overactivation. NUT ameliorated retinal functionality and morphology at early stages of RP in rd10 mice. This formulation could be useful as a neuroprotective approach for patients with RP in the future.

Degenerated Cones in Cultured Human Retinas Can Successfully Be Optogenetically Reactivated.

Biblical references aside, restoring vision to the blind has proven to be a major technical challenge. In recent years, considerable advances have been made towards this end, especially when retinal degeneration underlies the vision loss such as occurs with retinitis pigmentosa. Under these conditions, optogenetic therapies are a particularly promising line of inquiry where remaining retinal cells are made into “artificial photoreceptors”. However, this strategy is not without its challenges and a model system using human retinal explants would aid its continued development and refinement. Here, we cultured post-mortem human retinas and show that explants remain viable for around 7 days. Within this period, the cones lose their outer segments and thus their light sensitivity but remain electrophysiologically intact, displaying all the major ionic conductances one would expect for a vertebrate cone. We optogenetically restored light responses to these quiescent cones using a lentivirus vector constructed to express enhanced halorhodopsin under the control of the human arrestin promotor. In these ‘reactivated’ retinas, we show a light-induced horizontal cell to cone feedback signal in cones, indicating that transduced cones were able to transmit their light response across the synapse to horizontal cells, which generated a large enough response to send a signal back to the cones. Furthermore, we show ganglion cell light responses, suggesting the cultured explant’s condition is still good enough to support transmission of the transduced cone signal over the intermediate retinal layers to the final retinal output level. Together, these results show that cultured human retinas are an appropriate model system to test optogenetic vision restoration approaches and that cones which have lost their outer segment, a condition occurring during the early stages of retinitis pigmentosa, are appropriate targets for optogenetic vision restoration therapies.

Preservation of Visual Cortex Plasticity in Retinitis Pigmentosa

Retinitis Pigmentosa (RP) is a class of inherited disorders caused by the progressive death of photoreceptors in the retina. RP is still orphan of an effective treatment, with increasing optimism deriving from research aimed at arresting neurodegeneration or replacing light-responsive elements. All these therapeutic strategies rely on the functional integrity of the visual system downstream of photoreceptors. Whereas the inner retinal structure and optic radiation are known to be considerably preserved at least in early stages of RP, very little is known about the visual cortex. Remarkably, it remains completely unclear whether visual cortex plasticity is still present in RP. Using a well-established murine model of RP, the rd10 mouse, we report that visual cortical circuits retain high levels of plasticity, preserving their capability of input-dependent remodelling even at a late stage of retinal degeneration.

Microglia Mediate Synaptic Material Clearance at the Early Stage of Rats With Retinitis Pigmentosa.

Resident microglia are the main immune cells in the retina and play a key role in the pathogenesis of retinitis pigmentosa (RP). Many previous studies on the roles of microglia mainly focused on the neurotoxicity or neuroprotection of photoreceptors, while their contributions to synaptic remodeling of neuronal circuits in the retina of early RP remained unclarified. In the present study, we used Royal College of Surgeons (RCS) rats, a classic RP model characterized by progressive microglia activation and synapse loss, to investigate the constitutive effects of microglia on the synaptic lesions and ectopic neuritogenesis. Rod degeneration resulted in synapse disruption and loss in the outer plexiform layer (OPL) at the early stage of RP. Coincidentally, the resident microglia in the OPL increased phagocytosis and mainly engaged in phagocytic engulfment of postsynaptic mGluR6 of rod bipolar cells (RBCs). Complement pathway might be involved in clearance of postsynaptic elements of RBCs by microglia. We pharmacologically deleted microglia using a CSF1 receptor (CSF1R) inhibitor to confirm this finding, and found that it caused the accumulation of postsynaptic mGluR6 levels and increased the number and length of ectopic dendrites in the RBCs. Interestingly, the numbers of presynaptic sites expressing CtBP2 and colocalized puncta in the OPL of RCS rats were not affected by microglia elimination. However, sustained microglial depletion led to progressive functional deterioration in the retinal responses to light in RCS rats. Based on our results, microglia mediated the remodeling of RBCs by phagocytosing postsynaptic materials and inhibiting ectopic neuritogenesis, contributing to delay the deterioration of vision at the early stage of RP.

Development and evaluation of a visual aid using see-through display for patients with retinitis pigmentosa.

Patients in the early stage of retinitis pigmentosa (RP) suffer from night blindness and, therefore, have mobility problems at night. To assist such patients with walking in the dark, we developed a wearable visual aid utilizing a see-through display upon which assistive images from a high-sensitivity video camera are superimposed. We evaluated the efficacy of our new visual aid for RP patients. The device is equipped with a camera with a minimum illuminance of 0.08 lux and a view angle of 53°×40°. The experiment was conducted in a room with dimmed light (illuminance level 0.2-1.2 lux). Eight subjects with RP were instructed to arrive at a goal 16m away from the starting point, both with and without the device, passing through four 1.5-m-wide gates consisting of pairs of black square carpet pieces, white poles, red and white traffic cones and cardboard boxes with and without the device in a darkened room. Three gates, except for the boxes, which were nearest the goal, were randomly arranged along the x-axis at each trial. The number of trial failures and the time required to walk the course were assessed as outcomes. Seven of the 8 subjects could walk with the aid of the device without any failure. With the device, the number of trial failures significantly decreased in number (p<0.05) in all subjects. This device enabled the subjects to see objects that could not be recognized by the unaided eye. Our visual aid effectively assisted RP patients with night blindness.

Detection of retinitis pigmentosa by differential interference contrast microscopy.

Differential interference contrast microscopy is designed to image unstained and transparent specimens by enhancing the contrast resulting from the Nomarski prism-effected optical path difference. Retinitis pigmentosa, one of the most common inherited retinal diseases, is characterized by progressive loss of photoreceptors. In this study, Differential interference contrast microscopy was evaluated as a new and simple application for observation of the retinal photoreceptor layer and retinitis pigmentosa diagnostics and monitoring. Retinal tissues of Royal College of Surgeons rats and retinal-degeneration mice, both well-established animal models for the disease, were prepared as flatmounts and histological sections representing different elapsed times since the occurrence of the disease. Under the microscopy, the retinal flatmounts showed that the mosaic pattern of the photoreceptor layer was irregular and partly collapsed at the early stage of retinitis pigmentosa, and, by the advanced stage, amorphous. The histological sections, similarly, showed thinning of the photoreceptor layer at the early stage and loss of the outer nuclear layer by the advanced stage. To count and compare the number of photoreceptors in the normal and early-retinitis pigmentosa-stage tissues, an automated cell-counting program designed with MATLAB, a numerical computing language, using a morphological reconstruction method, was applied to the differential interference contrast microscopic images. The number of cells significantly decreased, on average, from 282 to 143 cells for the Royal College of Surgeons rats and from 255 to 170 for the retinal-degeneration mouse. We successfully demonstrated the potential of the differential interference contrast microscopy technique’s application to the diagnosis and monitoring of RP.

Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa

BackgroundThe purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease.MethodsA total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch’s membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL).ResultsThe IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, P<0.001), but hyperreflective foci in the ONL were observed in a significantly larger proportion of eyes in group Y than in group X (100% versus 69%, P<0.001).ConclusionHyperreflective foci in the INL were more frequently observed in retinas with the early stage of retinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa.

Thermal Stability of Rhodopsin and Progression of Retinitis Pigmentosa

Over 100 point mutations in the rhodopsin gene have been associated with retinitis pigmentosa (RP), a family of inherited visual disorders. Among these, we focused on characterizing the S186W mutation. We compared the thermal properties of the S186W mutant with another RP-causing mutant, D190N, and with WT rhodopsin. To assess thermal stability, we measured the rate of two thermal reactions contributing to the thermal decay of rhodopsin as follows: thermal isomerization of 11-cis-retinal and hydrolysis of the protonated Schiff base linkage between the 11-cis-retinal chromophore and opsin protein. We used UV-visible spectroscopy and HPLC to examine the kinetics of these reactions at 37 and 55 °C for WT and mutant rhodopsin purified from HEK293 cells. Compared with WT rhodopsin and the D190N mutant, the S186W mutation dramatically increases the rates of both thermal isomerization and dark state hydrolysis of the Schiff base by 1-2 orders of magnitude. The results suggest that the S186W mutant thermally destabilizes rhodopsin by disrupting a hydrogen bond network at the receptor's active site. The decrease in the thermal stability of dark state rhodopsin is likely to be associated with higher levels of dark noise that undermine the sensitivity of rhodopsin, potentially accounting for night blindness in the early stages of RP. Further studies of the thermal stability of additional pathogenic rhodopsin mutations in conjunction with clinical studies are expected to provide insight into the molecular mechanism of RP and test the correlation between rhodopsin's thermal stability and RP progression in patients.

Optical imaging of mitochondrial redox state in rodent model of retinitis pigmentosa

Oxidative stress (OS) and mitochondrial dysfunction contribute to photoreceptor cell loss in retinal degenerative disorders. The metabolic state of the retina in a rodent model of retinitis pigmentosa (RP) was investigated using a cryo-fluorescence imaging technique. The mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are autofluorescent and can be monitored without exogenous labels using optical techniques. The cryo-fluorescence redox imaging technique provides a quantitative assessment of the metabolism. More specifically, the ratio of the fluorescence intensity of these fluorophores (NADH/FAD), the NADH redox ratio (RR), is a marker of the metabolic state of the tissue. The NADH RR and retinal function were examined in an established rodent model of RP, the P23H rat compared to that of nondystrophic Sprague-Dawley (SD) rats. The NADH RR mean values were 1.11 ± 0.03 in the SD normal and 0.841 ± 0.01 in the P23H retina, indicating increased OS in the P23H retina. Electroretinographic data revealed a significant reduction in photoreceptor function in P23H animals compared to SD nozrmal rats. Thus, cryo-fluorescence redox imaging was used as a quantitative marker of OS in eyes from transgenic rats and demonstrated that alterations in the oxidative state of eyes occur during the early stages of RP.

ET-1 plasma levels and ocular blood flow in retinitis pigmentosaThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

Retinitis pigmentosa (RP) is an inherited retinal disorder clinically characterized by a pale, waxy optic nerve head, attenuated retinal blood vessels, and bone spicule pigment in the retina. Hemodynamic studies have demonstrated that RP is associated with a reduction in the retinal and choroidal blood flow. Retinal hemodynamic impairment is also present in early stages of RP, and various hypotheses have been advanced as to the cause. The authors studied 20 patients, 12 males and 8 females, aged 26-42 years (mean 35.1 years) and affected by simplex RP. The patients had a visual acuity of 0.9 +/- 0.1, visual field mean defect of -6.52 +/- 3.58 dB, and b-wave electroretinogram amplitude of 260.08 +/- 8.24 microV. An increase in plasma levels of endothelin-1 (ET-1) was found: 1.910 +/- 0.317 pg/mL versus 1.180 +/- 0.210 pg/mL in non-RP controls (p < 0.02). Moreover both an ocular and systemic vascular impairment was detected by means of color Doppler imaging and laser Doppler flowmetry performed during a cold pressor test. We found a correlation between the increase of ET-1 plasma levels in RP and the decrease of peak systolic velocity in the ophthalmic artery (p < 0.03) and in the posterior ciliary arteries (p < 0.006). It is thought that an increase of ET-1 and retinal oxygen levels in RP could lead to vasoconstriction and a decrease of the retinal blood flow, worsening the abiotrophic process.

Preservation of Macular Oscillatory Potentials in Eyes of Patients with Retinitis Pigmentosa and Normal Visual Acuity

To study the functional changes in the macula of the retina in the early stage of retinitis pigmentosa (RP), by analyzing each component of the focal macular electroretinogram (fmERG). fmERGs were recorded from 39 patients with RP with normal visual acuity (>1.0) under direct fundus observation using a modified infrared fundus camera and 5 degrees , 10 degrees , and 15 degrees stimulus spots. The amplitudes and implicit times of the a-wave, b-wave, and oscillatory potentials (OPs) in the patients with RP were compared to those from 30 age-similar normal control subjects. The amplitudes of the different components of the fmERGs in patients with RP ranged from severely reduced to normal. The degree of amplitude reduction increased as the size of the stimulus spot increased in the patients with RP. The relative amplitudes of the OPs (67% of the mean in normal subjects) were better preserved than that of the b-wave (46%) and the a-wave (39%) in a 10 degrees spot in the patients with RP. The relative preservation of the OPs in the patients with RP could be due to either the buffering effect of the large receptive fields of the OP generators or to the retinal remodeling after the progressive loss of photoreceptors. Recordings of each component of fmERG can provide important information on the different layers of the central retina in RP eyes and can add to the understanding of the pathophysiology of RP.

The Effects of Darkness on Retrobulbar Hemodynamics in Patients with Early Stages Retinitis Pigmentosa

To investigate the retrobulbar hemodynamic changes occurring in light and darkness in patients with early stages retinitis pigmentosa (RP). Eleven early stages RP patients were enrolled in the study. The peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI) and resistivity index (RI) of the ophthalmic artery (OA) and central retinal artery (CRA) were measured by color Doppler imaging in light and darkness. The results were compared with that of 10 age-matched normal subjects. PSV and EDV of the OA did not show significant differences in both groups. However, PSV and EDV of the CRA in RP patients decreased significantly in darkness (p = 0.001, p < 0.001, respectively). In addition, we found a significant increase in RI of the CRA in RP patients in darkness (p = 0.003). On the contrary, PSV and EDV of the CRA in control subjects showed a significant increase (p = 0.002, p < 0.001, respectively) and RI showed a significant decrease in darkness (p = 0.004). Darkness causes a decreased blood flow in the CRA in early stages of RP.

Contribuição diagnóstica da avaliação eletrofisiológica visual em pacientes atendidos em hospital universitário

OBJETIVO: Determinar a freqüência de diferentes categorias diagnósticas em um laboratório de eletrofisiologia visual clínica de um hospital universitário. MÉTODOS: Os pacientes participaram de um estudo transversal sendo submetidos a testes eletrodiagnósticos visuais entre outubro de 1998 e outubro de 2000 (N=570). Os exames de eletrorretinografia (ERG) foram realizados em 385 pacientes (68%) e de potenciais visuais evocados (PVE) por reversão de padrão e/ou flashes e varredura em 185 pacientes (32%). RESULTADOS: Após avaliação da eletrorretinografia, as categorias diagnósticas mais freqüentes foram identificadas na seguinte ordem: retinose pigmentária, doença de Stargardt, distrofia de cones, degeneração do tipo cone-bastonete, retinotoxicidade devido a vários agentes (cloroquina, tamoxifeno, etc) e trauma ocular, além de perdas visuais de causas idiopáticas. Em 23% dos casos, não foi possível obter o diagnóstico final ao primeiro exame. O grupo mais freqüente referido para o eletrorretinografia foi para documentar ou excluir as degenerações tapeto-retinianas (42%). Neste grupo, 110 casos de retinose pigmentária foram identificados: 91 casos isolados e 19 sindrômicos. Para o exame de potenciais visuais evocados, as categorias diagnósticas mais freqüentes foram: doenças que afetam somente o nervo óptico (atrofia de nervo óptico, neurites ópticas, edema de disco óptico, etc.); condições neurológicas afetando a via visual (esclerose múltipla, paralisia cerebral, trauma crânio-encefálico, tumores, etc.), condições neurológicas e/ou doenças oculares pediátricas (catarata congênita, deficiência visual cortical, glaucoma congênito, etc.), e opacidade de meios (leucoma, trauma ocular, etc.). CONCLUSÕES: A análise deste amplo grupo de pacientes, mostra as indicações mais freqüentes e significativas para registros eletrofisiológicos visuais e decisões diagnósticas. Vários diagnósticos podem ser de difícil conclusão sem os testes eletrofisiológicos visuais. Dentre essas doenças incluem-se estágios iniciais da retinose pigmentária, distrofia progressiva de cones, retinopatia tóxica sem alterações fundoscópicas, função de nervo óptico ou retiniana em opacidades de meios, envolvimento de nervo óptico em esclerose múltipla e avaliação da acuidade visual em doenças oculares infantis com ou sem alterações neurológicas.