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Biomedical subjects

Eugene de Juan

Publications and source records attributed to Eugene de Juan.

At least 19 recordsLinked to original sources
PubMed2006

A new model of experimental subretinal neovascularization in the rabbit.

Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 microl of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 microl of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 microl of Matrigel only; three rabbits used as controls received subretinal injections of 20 microl phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.

Animals↗
PubMed2006

Development, implantation, in vivo elution, and retrieval of a biocompatible, sustained release subretinal drug delivery system.

A biocompatible, sustained-release subretinal drug-delivery platform was developed to overcome the therapeutic accessibility limitations of current retinal disease treatments. The prototype implants were fabricated by coating nitinol, poly(methyl methacrylate) or chromic gut core filaments, with a drug-eluting polymer matrix. The polymer coatings are manufactured and coated by SurModics. The coating is a mixture of poly(butyl methacrylate) and poly(ethylene-co-vinyl acetate). The drug is either triamcinolone acetonide or sirolimus. The rods were successfully implanted into the subretinal space of 20/24 rabbits. Four rabbits were lost to early surgery from a dysfunctional infusion line and hemorrhage. No serious complications were observed during the 4-week follow-up period. Slight conjunctival redness was reported in all rabbits by 1-day follow-up, but the redness had subsided by the following week. Intraocular lens touch occurred in six rabbits during the implantations; of these, four had a lensectomy at the time of surgery, and the remaining two developed cataract. Corneal edema developed in three rabbits by 1-week follow-up, but subsided within 2 weeks. Initial observations of the implantation and elution characteristics revealed that the implants are well tolerated by the retinal tissue and that the implant can elute triamcinolone acetonide for a period of at least 4 weeks without eliciting an inflammatory response or complications. There were adverse clinical indications with the sirolimus-loaded implants at the delivered dose. Device retrieval required an uncomplicated surgical procedure, and revealed no associated or adherent tissue. Implant drug content analysis and opacity changes to the polymer matrix coating following retrieval demonstrated the sustained elution of the drug.

Animals↗
PubMed2006

Application of a new subretinal injection device in the dog.

The use of a new subretinal injection device (RetinaJect Subretinal Cannula, SurModics, Inc., Eden Prairie, MN) to access the subretinal space in the canine model was evaluated. Subretinal injections were performed in 33 mongrel dogs between 2 and 52 months of age (median = 9 months). In 5 normal dogs the injection of 150 microl saline or India ink occurred by using a conventional subretinal injection device (CSID) with a 30-gauge anterior chamber irrigating cannula. The sclera had to be surgically exposed and penetrated before the subretinal injection with the CSID could occur. After removing the CSID, the conjunctiva over the sclerotomy site had to be closed. In a second group of 28 dogs [16 normals, 10 RPE65 mutants, and 2 with progressive rod cone degeneration (prcd)], the 25-gauge needle of the RetinaJect was used to penetrate the conjunctiva and the sclera. Once the tip of the needle was close to the retinal surface, a 39-gauge polyimide cannula was extended and brought into apposition with the retina for the subsequent subretinal injection of 150 microl saline, India ink, or adeno-associated virus (AAV). No closure of the conjunctiva was required. The animals were clinically monitored between 1 and 59 weeks after surgery. From this second group 25 eyes were harvested for routine histological analysis either immediately after surgery or after a clinical observation time of between 1 and 40 weeks. Both devices provided equally successful access to the subretinal space. The main advantage of the RetinaJect was that no surgical dissection was required; this led to a shorter procedure time and milder postoperative conjunctival swelling. In summary, the use of the RetinaJect can be recommended as an alternative to the CSID for subretinal injections in dogs.

Animals↗
PubMed2005

Fabrication, implantation, elution, and retrieval of a steroid-loaded polycaprolactone subretinal implant.

A subretinal drug delivery system was developed to overcome the limitations of current treatments for retinal disease. A rod-shaped implant was made by embedding the corticosteroid triamcinolone acetonide within a biodegradable polycaprolactone polymer matrix. The implant was fabricated by homogeneously mixing the polymer and drug in solvent. The mixture was then dried, melted, and extruded, and the prepared solid form was drawn into a filament. The rods were mechanically sectioned to a length of 2 mm with a diameter of up to 320 microm. The rods were successfully implanted into the subretinal space of six rabbits. No complications were observed during the 4-week follow-up period. Initial observations of the implantation and elution characteristics revealed that polycaprolactone is well tolerated by the retinal tissue and that the implant can elute steroid for a period of at least 4 weeks without eliciting inflammatory response or complications. In vitro drug elution rates of different polymer to drug ratios and geometries into a balanced salt solution/bovine serum albumin (1%) solution showed an early rapid-release phase and late first-order phase. Histology and device retrieval after implantation revealed minimal encapsulation and good preservation of cellular morphology during the follow-up period and a more fibrous polymer microstructure of the implant.

Absorbable Implants↗
PubMed2005

Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats.

Previous studies evaluating neural stem cells transplanted into the mature retina have demonstrated limited levels of graft-host integration and photoreceptor differentiation. The purpose of this investigation is to enhance photoreceptor cell differentiation and integration of retinal progenitor cells (RPC) following subretinal transplantation into retinal degenerate rats by optimization of isolation, expansion, and transplantation procedures. RPCs were isolated from human placental alkaline phosphatase (hPAP)-positive embryonic day 17 (E17) rat retina and expanded in serum-free defined media. RPCs at passage 2 underwent in vitro induction with all trans retinoic acid or were transplanted into the subretinal space of post-natal day (P) 17 S334ter-3 and S334ter-5 transgenic rats. Animals were examined post-operatively by ophthalmoscopy and optical coherence tomography (OCT) at weeks 1 and 4. Differentiation profiles of RPCs, both in vitro and in vivo were analysed microscopically by immunohistochemistry for various retinal cell specific markers. Our results demonstrated that the majority of passage 2 RPCs differentiated into retina-specific neurons expressing rhodopsin after in vitro induction. Following subretinal transplantation, grafted cells formed a multi-layer cellular sheet in the subretinal space in both S334ter-3 and S334ter-5 rats. Prominent retina-specific neuronal differentiation was observed in both rat lines as evidenced by recoverin or rhodopsin staining in 80% of grafted cells. Less than 5% of the grafted cells expressed glial fibrillary acidic protein. Synapsin-1 (label for nerve terminals) positive neural processes were present at the graft-host interface. Expression profiles of the grafted RPCs were similar to those of RPCs induced to differentiate in vitro using all-trans retinoic acid. In contrast to our previous study, grafted RPCs can demonstrate extensive rhodopsin expression, organize into layers, and show some features of apparent integration with the host retina following subretinal transplantation in slow and fast retinal degenerate rats. The similarity of the in vitro and in vivo RPC differentiation profiles suggests that intrinsic signals may have a significant contribution to RPC cell fate determination.

Animals↗
PubMed2005

Outcomes of 140 consecutive cases of 25-gauge transconjunctival surgery for posterior segment disease.

PURPOSE: To evaluate the safety and efficacy of 25-gauge instrumentation for a variety of vitreoretinal conditions on previously nonvitrectomized eyes. DESIGN: Single-center, retrospective, interventional case series. PARTICIPANTS: One-hundred forty eyes of 140 patients were evaluated at the Doheny Retina Institute from July 2002 to July 2003. INTERVENTION: All patients underwent surgical procedures using the Millennium 25-gauge Transconjunctival Standard Vitrectomy system. Twenty eyes (14.3%) underwent procedures without vitrectomy. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), intraocular pressure, surgical time, postoperative inflammation, complications, and number of sutured sites. RESULTS: No intraoperative complications were noted. No cases required conversion to 20-gauge machines. Ten cases (7.1%) involved single-site sclerotomy suture placement due to bleb formation at the conclusion of the procedure, but 5 of these entry sites were enlarged to facilitate larger instrumentation for tissue manipulation. Median VA improved from 20/250 (logarithm of the minimum angle of resolution, 1.08+/-0.47) preoperatively to 20/60 (0.47+/-0.30) (P<0.0001) at final visit. Mean follow-up was 33.8+/-9.7 weeks, and all eyes were observed for a minimum of 12 weeks. Mean total surgical time was 17.4+/-6.9 minutes. Intraocular pressures remained stable throughout the postoperative course. Five eyes (3.8%) presented on day 1 with shallow choroidal detachments, but all resolved by day 7, and none required volume infusion during the postoperative period. All but one of these cases was within the first 50 procedures performed. No detectable inflammation was noted in any eyes by 4 weeks postoperatively. No case of retinal detachment or endophthalmitis was recorded. CONCLUSIONS: Transconjunctival surgery using 25-gauge instrumentation may hasten postoperative recovery by decreasing overall surgical time and postoperative inflammation. Procedures requiring minimal intraocular manipulation did not require sutures and, thus, may be better suited for this surgical modality.

Aged↗
PubMed2005

Rapid recurrence of geographic atrophy after full macular translocation for nonexudative age-related macular degeneration.

OBJECTIVE: To report the recurrence of geographic atrophy (GA) in a patient with nonexudative age-related macular degeneration (AMD) after full macular translocation. DESIGN: Observational case report. METHODS: Review of the clinical, photographic, and angiographic records of a patient with GA who underwent full macular translocation. MAIN OUTCOME MEASURES: Progression of GA. RESULTS: A 73-year-old man with GA secondary to nonexudative AMD underwent a macular translocation with 360 peripheral retinectomy (MT 360) in his left eye. On postoperative month 4, fundus photography showed subtle alterations of the pigment underneath the translocated foveal region. On postoperative month 9, the visual acuity worsened to preoperative levels and there was frank retinal pigment epithelium atrophy involving the new macular region. CONCLUSIONS: The rapid recurrence and development of GA in the translocated fovea after MT 360 raise new questions regarding the pathogenesis of GA. They also raise concerns regarding the use of MT 360 in the management of nonexudative AMD.

Aged↗
PubMed2004

Macular translocation in patients with recurrent subfoveal choroidal neovascularization after laser photocoagulation for nonsubfoveal choroidal neovascularization.

PURPOSE: To report visual outcomes and to examine surgical factors affecting outcomes in patients undergoing macular translocation for recurrent subfoveal choroidal neovascularization after laser photocoagulation for nonsubfoveal choroidal neovascularization. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: A consecutive series of 31 eyes of 29 patients who underwent macular translocation for recurrent subfoveal choroidal neovascularization after laser photocoagulation for nonsubfoveal choroidal neovascularization. INTERVENTION: Inferior macular translocation with punctate retinotomy performed by a single surgeon. OUTCOME MEASURES: Surgical and visual outcomes at 3 and 6 months after surgery and complications data are reported. Associations between surgical factors and visual outcomes were analyzed statistically. RESULTS: Effective translocation was achieved in 77.4% of eyes. At 6 months, 54% of eyes achieved visual acuity (VA) better than 20/100, and 46% of eyes gained the equivalent of > or =2 Early Treatment Diabetic Retinopathy Study lines of vision. No association between size of recurrent choroidal neovascularization and visual outcome was identified. Eyes with a larger scar size experienced lower VA at 3 and 6 months, but scar size was not associated with change in VA at 3 and 6 months. Subretinal dissection during surgery to detach the macula was required in 8 of 31 eyes and was associated with a significantly increased incidence of peripheral retinal breaks. However, there was no difference in either VA or change in VA in eyes with and without subretinal dissection. Retinal detachment (RD) occurred in 6 of 31 eyes. No significant difference in the RD rate was observed between groups with or without subretinal dissection (P = 0.30). CONCLUSION: Our pilot data suggest that macular translocation can result in favorable surgical outcomes in patients with recurrent subfoveal choroidal neovascularization after laser photocoagulation for nonsubfoveal choroidal neovascularization. Use of subretinal dissection intraoperatively in these patients does not seem to affect visual outcome adversely, but may be associated with increased risk of peripheral retinal breaks.

Adult↗
PubMed2004

Effects of intravitreal indocyanine green injection in rabbits.

PURPOSE: To report the clinical, electrophysiologic, and histologic findings of different concentrations of indocyanine green (ICG) injected into the vitreous cavity of rabbit eyes. METHODS: Forty-two rabbits underwent intravitreal injection of 0.1 mL of ICG in three different concentrations: 0.5 mg/mL (250 mOsm), 5 mg/mL (270 mOsm), and 25 mg/mL (170 mOsm). Fellow eyes were injected with 0.1 mL of balanced salt solution. Biomicroscopy, ophthalmoscopy, electroretinography, fluorescein angiography, and histologic evaluation were performed. RESULTS: Eyes injected with 0.5 mg/mL of ICG showed b-wave latency delay on the first day after injection. Eyes injected with 5 mg/mL of ICG showed b-wave latency delay and decreased b-wave amplitude on the first and seventh days after injection; delayed a-wave latency on the first day after injection was also observed. Eyes injected with 25 mg/mL of ICG showed b- and a-wave amplitude and latency abnormalities during the entire follow-up. Direct correlation of increasing retinal edema proportional to the progressively increasing ICG concentrations was shown on histologic evaluation. CONCLUSION: Intravitreal ICG injection in rabbit eyes may impair retinal function and morphology proportional to the progressively increasing ICG dosages.

Animals↗
PubMed2004

Effects of indocyanine green injection on the retinal surface and into the subretinal space in rabbits.

PURPOSE: To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the subretinal space of rabbit eyes. METHODS: Twenty-two Dutch-belted rabbits underwent two-port vitrectomy followed by injection of ICG (5 mg/mL) on the retinal surface and into the subretinal space. Balanced salt solution (BSS) was also injected subretinally. The locations where ICG was delivered (both epiretinal and subretinal) were exposed to light from an endoilluminator for 7 minutes. The animals were examined at 1, 7, and 14 days after surgery. The eyes were studied by fluorescein angiography as well as light and electron microscopy. RESULTS: No damage was observed after epiretinal ICG injection, but subretinal ICG injection resulted in damage to the outer nuclear layer, photoreceptor inner and outer segments, and retinal pigment epithelium. This damage was more severe with longer follow-up. Control experiments without ICG, in which balanced salt solution was injected into the subretinal space or light was delivered on the epiretinal surface, demonstrated only damage to the photoreceptor outer segments. CONCLUSION: Subretinal delivery of ICG (5 mg/mL) in rabbits induces retinal pigment epithelium, photoreceptor inner and outer segment, and outer nuclear layer damage. These mechanisms of damage may explain the retinal pigment epithelium changes that are sometimes seen after ICG-assisted internal limiting membrane peeling in humans.

Animals↗
PubMed2003

Limited macular translocation for the management of subfoveal choroidal neovascularization after photodynamic therapy.

PURPOSE: To report our initial experience of limited macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration following photodynamic therapy with verteporfin. DESIGN: Interventional case series. METHODS: Retrospective review of four eyes of four consecutive patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration who underwent effective limited macular translocation following photodynamic therapy. The mean logarithm of minimal angle of resolution preoperative best-corrected visual acuity was 20/190 (range, 20/150 to 20/200), and in all eyes the visual acuity was 20/150 or worse. The major outcome measures were postoperative visual acuity and complications related to the surgery. RESULTS: The mean postoperative follow-up was 6.75 months (range, 6-8 months). Postoperative best-corrected visual acuity improved by 2 or more Snellen lines of visual acuity in three of four eyes (75%) and remained within 1 line in one of four eyes (25%). The mean postoperative best-corrected visual acuity was 20/100 (range, 20/40 to 20/150), and in two of the four eyes (50%) the visual acuity achieved was 20/100 or better. No complication was observed. CONCLUSIONS: Limited macular translocation may be a viable option in patients who have previously undergone photodynamic therapy.

Aged↗
PubMed2003

Combined phacoemulsification, intraocular lens implantation, and vitrectomy for eyes with coexisting cataract and vitreoretinal pathology.

PURPOSE: To report the preoperative, intraoperative, and postoperative outcomes of combining phacoemulsification and posterior chamber intraocular lens (IOL) implantation with pars plana vitrectomy in eyes with significant cataract and coexisting vitreoretinal pathology. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Charts of patients undergoing combined procedures at the Wilmer Ophthalmologic Institute between March 1995 and May 2000 were reviewed. RESULTS: In all, 122 eyes of 111 patients were identified. Patient ages ranged from 27 to 89 years (mean 65). Forty-three eyes had diabetic retinopathy; 11 had undergone vitrectomy previously. Macular pathology (hole, membrane, choridal neovascularization) was present in 69 eyes. The most common indications for surgery were diabetic vitreous hemorrhage, macular hole, epiretinal membrane, and retinal detachment. In all cases, phacoemulsification and IOL implantation were performed before vitreoretinal surgery. Preoperative vision ranged from 20/30 to light perception and postoperative vision ranged from 20/20 to no light perception. In 105 patients vision improved, in 7 there was no change, and in 10 vision decreased. Postoperative complications included opacification of the posterior capsule, increased intraocular pressure, corneal epithelial defects, vitreous hemorrhage, retinal detachment and iris capture by the IOL. CONCLUSIONS: Combined surgery is a reasonable alternative in selected patients. Techniques that may simplify surgery and reduce complications include: careful, limited, curvilinear capsulorhexis; in-the-bag placement of IOLs; use of IOLs with larger optics; suturing of cataract wounds before vitrectomy; use of miotics and avoidance of long-acting dilating drops in patients with intravitreal gas; and use of wide-field viewing systems.

Adult↗
PubMed2003

Visual perception in a blind subject with a chronic microelectronic retinal prosthesis.

A retinal prosthesis was permanently implanted in the eye of a completely blind test subject. This report details the results from the first 10 weeks of testing with the implant subject. The implanted device included an extraocular case to hold electronics, an intraocular electrode array (platinum disks, 4 x 4 arrangement) designed to interface with the retina, and a cable to connect the electronics case to the electrode array. The subject was able to see perceptions of light (spots) on all 16 electrodes of the array. In addition, the subject was able to use a camera to detect the presence or absence of ambient light, to detect motion, and to recognize simple shapes.

Aged↗
PubMed2003

Autologous transplantation of retinal pigment epithelium after mechanical debridement of Bruch's membrane.

PURPOSE: To determine whether transplantation of autologous retinal pigment epithelium (RPE) will prevent atrophy of the choriocapillaris and loss of photoreceptors in an area in which the RPE has been mechanically debrided from Bruch's membrane. METHODS: Abrasive debridement of RPE was performed with a metal cannula after localized retinal bleb detachments in two separate areas of the rabbit retina. The RPE cell suspension aspirated from one of the debridement sites was transplanted to the other. The debridement-only site served as control. The transplant and control sites were evaluated after 30 days by color fundus photography, fluorescein angiography, light microscopy and transmission electron microscopy. RESULTS: Compared with debridement only, debridement plus transplantation of RPE resulted in more complete repopulation of the bare Bruch's membrane surface with relative preservation of choriocapillaris and photoreceptors. CONCLUSION: Autologous transplantation of RPE onto an abrasively debrided Bruch's membrane decreases choriocapillaris atrophy and photoreceptor loss.

Animals↗
PubMed2003

Intraoperative ketorolac and eye pain after viteoretinal surgery: a prospective, randomized, placebo-controlled study.

PURPOSE: To compare the efficacy of one intraoperative dose of intravenous ketorolac tromethamine to saline placebo in controlling postoperative eye pain, nausea, and sedation following vitreoretinal surgery. STUDY DESIGN: Prospective, randomized, placebo-controlled clinical trial. METHODS: One hundred fourteen vitreoretinal surgical patients were randomized over a 7-month period to a single intraoperative intravenous dose of ketorolac tromethamine or placebo. All patients underwent surgery with intravenous sedation and retrobulbar anesthetic injection and had access to a standard postoperative analgesic regimen. After 2 and 5 hours, eye pain, nausea, and sedation levels were recorded using a standard visual analog scale. Analgesic requirements were tabulated. RESULTS: Patients given ketorolac were significantly less likely to have postoperative eye pain than were placebo-treated patients (P = 0.0043). Fewer ketorolac patients required postoperative analgesia than placebo patients did (P < 0.0001). Four ketorolac patients (7%) required a narcotic compared to 11 placebo patients (20%) (P < 0.0001). Fewer ketorolac patients experienced nausea and sedation than placebo patients did, but this difference was not statistically significant. CONCLUSION: Ketorolac tromethamine is an effective nonnarcotic choice for postoperative pain control following vitreoretinal surgery. Pain control is particularly important in this group of patients, whose compliance with postoperative procedures and positioning may significantly affect surgical outcome.

Aged↗
PubMed2003

Advances in the development of visual prostheses.

Visual prostheses are based on neuronal electrical stimulation at different locations along the visual pathway (ie, cortical, optic nerve, epiretinal, subretinal). In terms of retinal prostheses, advances in microtechnology have allowed for the development of sophisticated, high-density integrated circuit devices that may be implanted either in the subretinal or epiretinal space. Analogous to the cochlear implants for some forms of deafness, these devices could restore useful vision by converting visual information into patterns of electrical stimulation that would excite the remaining spared inner retinal neurons in patients with diseases such as retinitis pigmentosa and age-related macular degeneration. The different types of implants and recent results are discussed, but special emphasis is given to retinal implants.

Electric Stimulation↗
PubMed2003

The value of preoperative tests in the selection of blind patients for a permanent microelectronic implant.

PURPOSE: To determine the best candidates (ie, those requiring lowest current levels delivered to the retina to elicit visual perceptions) for long-term implantation of a microelectronic retinal implant through a series of preoperative visual, psychophysical, and electrophysiological tests. METHODS: This study protocol was granted an investigational device exemption by the Food and Drug Administration and was approved by the institutional review board at the University of Southern California. After informed consent was obtained, all subjects underwent the following preoperative tests: dark-adapted bright flash and 30-Hz flicker electroretinograms, electrical evoked responses (EERs) using a Burian-Allen corneal electrode to stimulate the globe, and psychophysical tests to evaluate the light and electrically elicited visual perceptions. Intraocular stimulation (IOS) of the retina was performed by an array of electrodes positioned on the internal limiting lamina. RESULTS: Lower vision correlated with less sensitive psychophysical responses (P<.0001). Lower vision and less sensitive psychophysical tests correlated with higher EER values for stimulus pulse widths of 2 ms (P<.0008) and 4 ms (P<.0002). Lower IOS currents correlated with more sensitive psychophysical responses (P<.02) and lower EER values at 4 ms (P<.04). CONCLUSIONS: Preoperative testing, especially psychophysical and electrophysiological tests to assess light and electrically driven visual responses, can help in evaluating patients for suitability for receiving a permanent microelectronic retinal implant. Further study is warranted.

Blindness↗