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Biomedical subjects

E de Juan

Publications and source records attributed to E de Juan.

At least 19 recordsLinked to original sources

Restoration of visual responses following transplantation of intact retinal sheets in rd mice.

PURPOSE: To correlate the functional outcomes with histologic findings following transplantation of fetal retinal sheets in rd mice, and to investigate the mechanisms of visual function restoration. METHODS: Twenty-one postnatal day 31-38 rd/rd (C3H/HeJ) mice were transplanted in one eye with retinal sheets (1.0 x 0.4 mm) obtained from embryonic day (E) 17 enhanced-green-fluorescent protein (eGFP) mice. Five mice underwent sham surgery without insertion of tissue. Four to five weeks after transplantation, visual responses to a light flash were recorded across the superior colliculus (SC) in seven eyes of seven transplanted mice that had clear corneas and lenses, and in all five sham surgery mice. Following the SC recording, the eyes were enucleated and processed for immunohistochemistry and examined using confocal microscopy. RESULTS: In three out of the seven eyes (43%), positive responses were recorded in the SC in an area topographically corresponding to the placement of the transplant in the host retina. No responses were recorded in the untreated eyes of 5-week-old and 9-week-old rd/rd mice, and in the 9-week-old sham surgery mice. In contrast, visual responses were recorded over the entire SC in normal eyes. The response onset latencies of the 3 transplanted mice with responses were similar to those of normal control mice. The organization of the graft did not appear to correlate as expected with the electrophysiology results, as eyes with well-organized, laminated grafts showed no response whereas the three light-responsive eyes had rosetted or disorganized grafts. All three light-responsive eyes demonstrated much higher levels of recoverin immunoreactivity in the host retina overlying the graft compared with untreated age-matched rd/rd mice. CONCLUSION: Restoration of the SC visual response does not appear to depend on a well-organized transplant in the rd mouse. Increased recoverin-staining in the host retina in light-responsive animals suggested that host cone rescue was the likely mechanism of vision restoration in this transplant model.

Animals↗

Visual and electrical evoked response recorded from subdural electrodes implanted above the visual cortex in normal dogs under two methods of anesthesia.

Sensitive methods are required to record electrical evoked potentials over the visual cortex to evaluate the efficacy and safety of a retinal prosthesis before it can be implanted on the retinal surface of patients afflicted by outer retinal diseases. This study was designed to examine subdural electrodes as a mean to evaluate cortical evoked potentials in response to light and electrical stimulation of the retina in three dogs under two methods of anesthesia-halothane and propofol. Results showed that subdural electrodes could be stabilized over the visual cortex for several (3-5) months, and that they were 6.95 times more sensitive than subdermal electrodes in recording cortical visual evoked potentials (VEPs) and 4.31 times more sensitive in recording cortical electrical evoked potentials under both methods of anesthesia. The waveforms' shape changed for each electrode in the subdural array during 6/6 (100%) and 20/38 (52%) multi-channel recording sessions under halothane and propofol, respectively. This change could point to a cortical retinotopic organization versus hierarchical organization of different cortical areas for a given retinal stimulus. In summary, subdural electrodes show promising results for recording visual and electrical evoked responses (EERs) and thus for evaluation of the retinal prosthesis.

Anesthesia↗

Morphometric analysis of the macula in eyes with geographic atrophy due to age-related macular degeneration.

PURPOSE: To evaluate the extent of neural cell death in eyes with geographic atrophy (GA). METHODS: Ten eyes with GA and five age-matched control eyes were selected for morphometric analysis. The nuclei of the ganglion cell, inner nuclear, and outer nuclear layers were counted in contiguous 100-microm segments from 1,500 microm nasal to 1,500 microm temporal to the fovea. RESULTS: The outer nuclear layer was most severely attenuated in eyes with GA, demonstrating a 76.9% reduction relative to control eyes (P < 0.0001). A significant loss of ganglion cells (by 30.7%) was also observed (P = 0.0008). There was no significant difference in the inner nuclear layer cells (P = 0.30). Among the GA eyes, the nuclei in all three layers were significantly reduced in segments in which the retinal pigment epithelium was completely absent (P </= 0.0003). CONCLUSION: Although the nuclei of the outer nuclear layer in eyes with GA were markedly attenuated, the nuclei of the inner nuclear layer were relatively preserved. There was also a significant reduction in ganglion cells in GA eyes, but considerable numbers remained even in the areas of complete retinal pigment epithelium atrophy. This finding suggests that therapies aimed at replacing outer nuclear function (such as neural retinal and retinal pigment epithelium transplantation or implantation of the intraocular retinal prosthesis) may be feasible for restoring vision in these patients.

Aged↗

Morphometric analysis of the macula in eyes with disciform age-related macular degeneration.

PURPOSE: To evaluate the extent of neural cell death in eyes with disciform age-related macular degeneration. METHODS: Six eyes with disciform degeneration at various stages and five age-matched control eyes were selected for morphometric analysis using digitized light microscopic images. Disciform scars were classified as subneurosensory retinal, subretinal pigment epithelial, or combined lesions. The nuclei of the ganglion cell, inner nuclear, and outer nuclear layers were counted in contiguous 100 microm segments spanning a distance from 1,500 microm nasal to 1,500 microm temporal to the fovea. RESULTS: The outer nuclear layer was most severely attenuated in eyes with disciform scars, demonstrating a 69.4% reduction in cell number relative to control eyes. A loss in retinal ganglion cells (by 7.3%) and an increase in inner nuclear layer cells (by 10%) were observed, but these changes were not significant. Photoreceptor loss was most pronounced when the disciform scar was not covered by the retinal pigment epithelium. CONCLUSION: The nuclei of the outer nuclear layer are significantly attenuated in eyes with disciform age-related macular degeneration, while the ganglion cell and inner nuclear layers are relatively preserved. These findings suggest that replacement of outer nuclear function, by either retinal transplantation or implantation of the intraocular retinal prosthesis, might be a feasible therapeutic option for patients with this condition.

Aged↗

Initial experience of inferior limited macular translocation for subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration.

PURPOSE: To report our initial experience of inferior limited macular translocation in patients with subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration. METHODS: We conducted a retrospective study of 23 eyes of 22 patients with choroidal neovascularization involving the foveal center secondary to pathologic myopia (11 eyes), ocular histoplasmosis syndrome (four eyes), angioid streaks (four eyes), idiopathic neovascularization (three eyes), and multifocal choroiditis (one eye), in which the fovea was moved inferiorly by means of limited macular translocation surgery. The mean preoperative best-corrected visual acuity was 20/150, and in five of 23 eyes (21.7%) the visual acuity was 20/80 or better. The major outcome measures were preoperative and postoperative visual acuity, postoperative foveal displacement, and complications related to the surgery. RESULTS: The mean postoperative follow-up was 10.82 months (range, 6 to 18 months). Postoperative best-corrected visual acuity improved by 2 or more Snellen lines of visual acuity in 11 of 23 eyes (47.82%), remained within 1 line in seven of 23 eyes (30.43%), and worsened 2 or more lines of vision in five of 23 eyes (21.74%). The mean postoperative best-corrected visual acuity was 20/100, and in 12 of the 23 eyes (52.17%) the visual acuity achieved was 20/80 or better. Retinal detachment was the most frequent complication and occurred in six eyes (26%). CONCLUSIONS: Our initial experience with limited macular translocation shows that this treatment modality offers the potential to improve visual function in some eyes with subfoveal choroidal neovascularization secondary to myopia, ocular histoplasmosis syndrome, angioid streaks, idiopathic neovascularization, and multifocal choroiditis. Although longer and more complete follow-up is needed, the results of this initial series warrant further studies to define the precise role of macular translocation in the management of these conditions.

Adult↗

Limited macular translocation for the management of subfoveal retinal pigment epithelial loss after submacular surgery.

PURPOSE: To report a case of subfoveal retinal pigment epithelial (retinal pigment epithelium) loss after submacular surgery managed successfully by limited macular translocation. METHODS: Case report. RESULTS: A 28-year-old woman presented with a visual acuity of 20/100 caused by subfoveal choroidal neovas-cularization secondary to ocular histoplasmosis syndrome. Submacular resection of the choroidal neovascularization was complicated by inadvertent retinal pigment epithelium loss from beneath the foveal center. She underwent limited macular translocation 5 days after the initial surgery and had successful displacement of the fovea to an area inferior to the retinal pigment epithelium defect. Her visual acuity was 20/60 4 months postoperatively. CONCLUSION: This report demonstrates the feasibility of using limited macular translocation for the management of eyes with central retinal pigment epithelium defect after submacular surgery and extends the clinical indications for limited macular translocation.

Adult↗

Macular translocation: unifying concepts, terminology, and classification.

PURPOSE: To describe some unifying concepts, terminology, and classification of macular translocation so as to facilitate communication within the scientific community. METHODS: A panel of ophthalmologists with expertise in macular translocation reviewed available data and developed some unifying concepts, terminology, and classification of macular translocation. RESULTS: Macular translocation may be defined as any surgery that has a primary goal of relocating the central neurosensory retina or fovea intraoperatively or postoperatively specifically for the management of macular disease. It may be classified according to the size of the retinotomy and, where applicable, the technique of chorioscleral shortening used. The direction of macular translocation is denoted by the movement of the neurosensory macula relative to the underlying tissues. Effective macular translocation may be defined as successful intraoperative or postoperative relocation of the fovea overlying a subfoveal lesion to an area outside the border of the lesion. The concepts of minimum desired translocation and median postoperative foveal displacement can give some useful idea of the likelihood of effective macular translocation before surgery. CONCLUSIONS: Use of a common standardized terminology for macular translocation will facilitate communication within the scientific community and enhance further research in this area. However, the definitions, terms, classification, and concepts concerning macular translocation are likely to continue to evolve as macular translocation undergoes further modifications and refinements.

Humans↗

Transient formed visual hallucinations following macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To report the occurrence of transient formed visual hallucinations following macular translocation. METHODS: Two case reports. RESULTS: Two white women aged 84 and 83 years with bilateral age-related macular degeneration and unilateral subfoveal choroidal neovascularization underwent macular translocation with punctate retinotomy (limited macular translocation) and chorioscleral infolding in the eye with neovascularization. They complained of formed visual hallucinations which began within 24 hours following macular translocation and ceased 7 and 3 days postoperatively, respectively. Their symptoms occurred in the presence of normal cognition, orientation and insight, were not associated with other psychiatric symptoms, and were characteristic of Charles Bonnet syndrome (CBS). CONCLUSION: The temporary deliberate retinal detachment and/or poor vision following macular translocation may be associated with postoperative CBS, and this report extends the spectrum of conditions associated with CBS.

Aged↗

Effective nasal limited macular translocation.

PURPOSE: To describe a case of effective foveal displacement toward the optic disk (nasal limited macular translocation) in a patient with a large subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: Case report. RESULTS: A 77-year-old white man presented with decreased vision of 20/400 due to subfoveal predominantly occult CNV secondary to age-related macular degeneration in the left eye. The CNV, measuring 9 Macular Photocoagulation Study disk areas in size, was centered temporally relative to the fovea with a minimum desired translocation of 650 microm for nasal macular translocation. The patient underwent nasal LMT with punctate retinotomy and temporal chorioscleral infolding, followed by postoperative head-positioning on his right side. Effective LMT was achieved with a postoperative nasal foveal displacement of 1400 microm. The entire CNV was ablated with laser photocoagulation postoperatively. His vision improved to 20/40 6 months postoperatively. CONCLUSION: Nasal LMT is feasible and may be considered in patients with subfoveal CNV centered temporally relative to the fovea.

Aged↗

Diplopia after limited macular translocation surgery.

PURPOSE: Full macular translocation surgery relocates the fovea away from choroidal neovascularization, inducing significant postoperative torsional diplopia. In "limited macular translocation," a saline-induced retinal detachment is followed by scleral imbrication with mattress sutures and spontaneous retinal reattachment. In this study, diplopia was characterized in patients treated with limited macular translocation. METHODS: Two surgeons performed retinal translocation surgery on 250 patients over an 18-month time span. The extent and direction of the retinal translocation, and the amount and location of scleral imbrication, were recorded. All patients complaining of diplopia were referred for ocular motility evaluation and treatment. RESULTS: Thirteen (5.2%) patients complained of occasional or constant diplopia. Imbricating sutures were placed supero-temporally in all cases. Inferior foveal translocation ranged from 200 to 2115 microm (median, 1750 microm). Visual acuity ranged from 20/40 to 20/400 in the operated eye. Prism-and-cover testing underestimated the strabismus when compared with subjective testing. In 3 patients, there was no shift on alternate-cover testing despite binocular diplopia. Excyclotorsion ranged from 0 degrees to 16 degrees. Diplopia resolved in 10 cases with prism; 3 required an occlusive filter for distortion or aniseikonia. One patient underwent successful strabismus surgery to eliminate dependence on prism glasses. CONCLUSIONS: Limited macular translocation only rarely produces symptomatic diplopia. Suprisingly, traditional prism-and-cover testing does not reliably quantify the misalignment. This may result from the combination of a persistent macular scotoma and a repositioned fovea relative to the peripheral retina. Prism therapy is generally satisfactory in the absence of retinal distortion or aniseikonia.

Aged↗

Eye pain after vitreoretinal surgery: a prospective study of 185 patients.

PURPOSE: To assess subjective levels of eye pain, nausea, and sedation following vitreoretinal surgery performed with intravenous sedation and retrobulbar anesthesia. METHODS: One hundred eighty-five consecutive patients who underwent vitreoretinal surgery and had access to a standard postoperative analgesic regimen prospectively quantified levels of eye pain, nausea, and sedation 2 hours and 5 hours after surgery by using a standard visual analog scale. Analgesic requests were recorded. Responses were statistically analyzed. RESULTS: Fifty-six percent of patients had some eye pain after vitreoretinal surgery; 48% of patients requested an analgesic within 5 hours after surgery. Twenty-seven percent of patients required narcotic analgesia. There was a significant relationship between the presence of eye pain and surgery duration of >2 hours (P < 0.02). Sixteen percent of patients had postoperative nausea, which more likely occurred in those who received a narcotic analgesic (P < 0.02). Eighty percent of patients had postoperative sedation, which more likely occurred in those who received a narcotic analgesic (P < 0.02). CONCLUSION: One half of individuals undergoing vitreoretinal surgery, especially those who have lengthy procedures (>2 hours), will request pain medication within 5 hours after surgery; one half of these patients will need narcotic analgesia for pain control. Narcotics may result in nausea and sedation.

Aged↗

Light-driven retinal ganglion cell responses in blind rd mice after neural retinal transplantation.

PURPOSE: Light-elicited retinal ganglion cell (RGC) responses after fetal neural retinal transplantation have not been demonstrated in animal or human subjects blind from outer retinal degeneration, despite apparent morphologic success. This study was designed to test the hypothesis that the functional success of retinal transplantation may be enhanced by using a young host retina (13 days old). METHODS: At postnatal day (P)13 C3H/HeJ (rd/rd) retinal degenerate mice received a subretinal transplant, in one eye only, of neural retinal tissue isolated from newborn normal C57/BL6J mice. Between 33 and 35 days after transplantation, local electroretinograms (ERGs) and ganglion cell responses were recorded directly from the retinal surface using a differential bipolar surface electrode. Measurements were performed both with and without light stimulation. Similar recordings were also performed in age-matched eyes subjected to sham transplantation, in control eyes that were not subjected to surgery, and in animals eyes that underwent transplantation at 8 weeks of age. After the recordings, the eyes were processed for light and transmission electron microscopy. RESULTS: Three of 10 mice showed bursts of ganglion cell action potentials (ON response only) as well as recordable intraocular ERGs over the transplant in response to 1-second and 200-msec light stimuli. Light-driven ganglion cell responses could not be recorded in areas outside the transplant in all transplant-recipient eyes, age-matched control eyes, and sham-transplantation eyes. Light responses also could not be recorded in animal eyes that received transplants at an older age (8 weeks). Electron microscopic examination confirmed the presence of photoreceptor outer segments in the areas affected by transplantation. CONCLUSIONS: This study demonstrates the presence of light-driven ganglion cell responses after subretinal transplantation in a retinal degenerate model. This finding may reflect functional integration of the transplant with the host, but a rescue effect on remaining host photoreceptors cannot be ruled out. The findings suggest, however, that modification of host parameters, such as host age, may be important approaches for improving the functional success of retinal transplantation.

Action Potentials↗

Normalization of retinal vascular permeability in experimental diabetes with genistein.

PURPOSE: To study the effects of genistein, a tyrosine kinase inhibitor, on retinal vascular permeability in an experimental diabetic rat model. METHODS: Seventy-two rats were equally divided into four groups: (1) nondiabetic control group, (2) diabetic control group, (3) diabetic rats receiving 150 mg genistein/kg food, and (4) diabetic rats receiving 300 mg genistein/kg food. Diabetes was induced by streptozotocin injection in the three diabetic groups. Rats were fed diets with or without genistein and followed for 6 months. Retinal vascular permeability was assessed by measuring radiolabeled sucrose leakage into the retina and by Western blot analysis for total retinal albumin. Retinal phosphotyrosine levels and proliferating cell nuclear antigen (PCNA) were also evaluated by Western blot analysis. RESULTS: Diabetic control rats had markedly increased retinal vascular leakage of radiolabeled sucrose compared with nondiabetic control rats. Diabetic rats receiving oral genistein had significantly less retinal vascular leakage of radiolabeled sucrose than diabetic control rats in a dose-response fashion. Diabetic control rats had increased levels of phosphotyrosine, retinal albumin, and PCNA by Western blot analysis compared with nondiabetic control rats. Rats receiving 300 mg of genistein had decreased retinal albumin by Western blot analysis. Western blot analysis demonstrated a dose-response decrease in retinal phosphotyrosine levels and PCNA in genistein-treated diabetic rats compared with diabetic control rats. CONCLUSIONS: Long-term oral administration of genistein significantly inhibits retinal vascular leakage in experimentally induced diabetic rats. Tyrosine kinase inhibition may be a useful pharmacological approach for the treatment of diabetic-induced retinal vascular leakage.

Administration, Oral↗

Retinal pigment epithelial autotransplantation: morphological changes in retina and choroid.

BACKGROUND: Replacement of degenerating retinal pigment epithelial (RPE) cells has been proposed to promote photoreceptor survival in retinal pigment epithelial disease. However, allografts of RPE have a higher rate of immunological rejection. The investigators studied the effects of autotransplantation of RPE on the morphological changes in photoreceptors and choriocapillaris. METHODS: RPE autotransplantation (wound type 1) was performed in 25 rabbits and compared with wounds following debridement of the RPE (wound type 2). Light and electron microscopy and scanning electron microscopy of choroidal vascular casts were performed at 3, 7, 14 and 30 days after surgery. Quantitative analysis of the choriocapillaris bed area was performed by automated image analysis and the results were analyzed by paired Student's t-test. RESULTS: Retinal pigment epithelium was found to be monolayered and ill-differentiated at day 7. Differentiation occurred at day 30, with preservation of photoreceptors and other layers of the neurosensory retina in type 1 wounds. Type 2 wounds showed atrophy of the regenerating retinal pigment epithelium at day 14 and day 30 with loss of overlying photoreceptor cell layer. There was significant choriocapillaris regeneration in type 1 wounds compared to the type 2 wounds at day 7 (P=0.045), day 14 (P=0.028) & day 30 (P=0.06). CONCLUSIONS: Retinal pigment epithelial autotransplantation significantly reduced photoreceptor degeneration and choriocapillaris atrophy associated with loss of retinal pigment epithelium. This procedure supports the hypothesis that RPE autotransplantation may be helpful in geographic atrophy and conditions requiring submacular surgery.

Animals↗

Herbimycin A in the treatment of experimental proliferative vitreoretinopathy: toxicity and efficacy study.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is partially caused by peptide growth factors, stimulating the cell by binding to a transmembrane tyrosine kinase receptor. We studied the effects of herbimycin A (HA), a tyrosine kinase inhibitor, in PVR. METHODS: Toxicity studies: Electroretinography and histological studies were performed after intravitreal injection of HA. Efficacy studies: Homologous rabbit dermal fibroblasts were injected intravitreally, followed by injection of HA. The presence of tractional retinal detachment (TRD) and severity of inflammation were assessed. RESULTS: Toxicity studies: Eyes injected with HA exhibited decrease in B-wave amplitude initially, with subsequent recovery. Histologically, damage to photoreceptors was evident after injection of high but not of low doses of HA. Efficacy studies: Inflammatory response and the development of TRD were significantly reduced with all doses of HA. CONCLUSIONS: HA (20 microM) was found to be effective and safe in preventing the development of inflammation and TRD.

Animals↗