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Biomedical subjects

M S Humayun

Publications and source records attributed to M S Humayun.

At least 19 recordsLinked to original sources
PubMed2000

The surgical management of hypotony.

OBJECTIVE: To study the effect of dissecting epiciliary proliferative tissue in eyes that are hypotonous. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Eight patients (nine eyes). MAIN OUTCOME MEASURES: Normalization of intraocular pressure and preservation of vision. METHODS: A chart review was conducted to locate all surgical procedures performed primarily for hypotony. Nine procedures on eight eyes of eight patients seen in the vitreoretinal service of the Wilmer Ophthalmological Institute were identified and included in this study. Six of these eyes had undergone prior surgery for retinal detachment in association with proliferative vitreoretinopathy, one had undergone surgery for retinal detachment in the setting of a ruptured globe, and two had undergone cataract surgery and coined the diagnoses of uveitis (juvenile rheumatoid arthritis and sarcoid). Dissection and removal of the epiciliary proliferative tissue and lens capsule was undertaken by two surgeons (EdJ and MSH) using either a pars plana or limbal approach. The main outcome measures were intraocular pressure (IOP) and visual acuity after an average follow-up of 26 months (range, 9-48 months). RESULTS: In the immediate postoperative period, all patients showed an increase in IOP (average increase of 6.3 mm Hg; range, 3-14 mmHg). This average increase in IOP decreased to 5.2 mmHg at 6 months and 4.2 mm Hg at 12 or more months of follow-up. The rate of the IOP decrease appeared to lessen with time, suggesting long-term stabilization. Visual acuity remained stable in all patients, although the final level of vision was low. CONCLUSIONS: Surgical intervention for hypotony with greater than 1 year follow-up continues to show elevated IOP in some patients, despite the fact that the large initial increase in IOP is not sustained. No eye had phthisis develop or became painful. However, no eye had marked improvement in vision. Further study is needed to uncover the main contributing factors that result in hypotony before IOP can be maintained for prolonged periods in more hypotonous eyes and before these eyes can regain more vision.

Adult↗
PubMed1999

Understanding the origin of visual percepts elicited by electrical stimulation of the human retina.

BACKGROUND: The success of a retinal prosthesis for patients with outer retinal degeneration (ORD) depends on the ability to electrically stimulate retinal cells other than photoreceptors. Experiments were undertaken in human volunteers to ascertain whether electrical stimulation of cells other than photoreceptors will result in the perception of light. METHODS: In two subjects, two areas of laser damage (argon green and krypton red) were created in an eye scheduled for exenteration due to recurrent cancer near the eye. In the operating room prior to exenteration, under local anesthesia, a hand-held stimulating device was inserted via the pars plana and positioned over the damaged areas and normal retina. Subjects' psychophysical responses to electrical stimulation were recorded. RESULTS: In both subjects, electrical stimulation produced the following perceptions. Normal retina: dark oval (subject 1), dark half-moon (subject 2); krypton red laser-treated retina: small, white light (both subjects); argon green laser treated retina: thin thread (subject 1), thin hook (subject 2). Histologic evaluation of the krypton red-treated retina showed damage confined to the outer retinal layers, while the argon green-treated area evinced damage to both the outer and the inner nuclear layers. CONCLUSION: The perception produced by electrical stimulation was dependent on the retinal cells present. Electrical stimulation of the krypton red-ablated area best simulated the electrically elicited visual perceptions of our blind, ORD patients, suggesting that the site of stimulation in blind patients is the inner retinal neurons.

Aged↗
PubMed1999

Pattern electrical stimulation of the human retina.

Experiments were conducted to study if electrical stimulation of the retinal surface can elicit visual sensation in individuals blind from end-stage retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Under local anesthesia, different stimulating electrodes were inserted through the eyewall and positioned over the surface of the retina. Subjects' psychophysical responses to electrical stimulation were recorded. Subjects perceived simple forms in response to pattern electrical stimulation of the retina. A non-flickering perception was created with stimulating frequencies between 40 and 50 Hz. The stimulation threshold was dependent on the targeted retinal area (macular versus extramacular).

Blindness↗
PubMed1999

Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy.

PURPOSE: To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS: A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS: The patient's vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION: Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.

Aged↗
PubMed1999

A computational model of electrical stimulation of the retinal ganglion cell.

Localized retinal electrical stimulation in blind volunteers results in discrete round visual percepts corresponding to the location of the stimulating electrode. The success of such an approach to provide useful vision depends on elucidating the neuronal target of surface electrical stimulation. To determine if electrodes preferentially stimulate ganglion cells directly below them or passing fibers from distant ganglion cells, we developed a compartmental model for electric field stimulation of the retinal ganglion cell (RGC). In this model a RGC is stimulated by extracellular electrical fields with active channels and realistic cell morphology derived directly from a neuronal tracing. Three membrane models were applied: a linear passive model, a Hodgkin-Huxley model with passive dendrites (HH), and a model composed of all active compartments (FCM) with five nonlinear ion channels. Idealized monopolar point and disk stimulating electrodes were positioned above the cell. For the HH and FCM models, the position of lowest cathodal threshold to propagate an action potential was over the soma. Brief (100 microseconds) cathodic stimuli were 20% (HH with disk electrode) to 73% (FCM with point-source) more effective over the soma than over the axon. In the passive model, the axon is preferentially stimulated versus the soma. Although it may be possible to electrically stimulate RGC's near their cell body at lower thresholds than at their axon, these differences are relatively small. Alternative explanations should be sought to explain the focal perceptions observed in previously reported patient trials.

Action Potentials↗
PubMed1999

Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs.

PURPOSE: Short-term pattern electrical stimulation of the retina via multielectrode arrays in humans blind from photoreceptor loss has shown that ambulatory vision and limited character recognition is possible. To develop an implantable retinal prosthesis that would provide useful vision, these results need to be sustained over a prolonged period of retinal electrical stimulation. As a first step toward this goal, the biocompatibility and the feasibility of surgically implanting an electrically inactive electrode array onto the retinal surface was tested. METHODS: A 5 x 5 electrode array (25 platinum disc-shaped electrodes in a silicone matrix) was implanted onto the retinal surface using retinal tacks in each of the 4 mixed-breed sighted dogs. Color fundus photography, fluorescein angiography, electroretinography, and visual evoked potentials were obtained preoperatively, at 1-week intervals for 2 weeks postoperatively, then at 2-week intervals up to 2 months postoperatively, and thereafter at 1-month intervals. One dog was killed at 2 months after implantation and a second dog after 3 months of implantation. Histologic evaluation of the retinas was performed. The remaining two dogs continue to be followed beyond 6 months after the implantation surgery. RESULTS: No retinal detachment, infection, or uncontrolled intraocular bleeding occurred in any of the animals. Retinal tacks and the retinal array remained firmly affixed to the retina throughout the follow-up period. Hyperpigmentation of the retinal pigment epithelium was observed only around the site of retinal tack insertion. No fibrous encapsulation of the implant or intraocular inflammation was visible. A- and b-wave amplitudes of the electroretinogram were depressed at the first postoperative week testing but recovered over the ensuing 1 week and were not statistically different from the normal unoperated fellow eye throughout the postoperative period. N1 and P1 wave amplitudes of the visual evoked potentials were not significantly different from the normal fellow eyes at any of the postoperative test intervals. Fluorescein angiography showed that the entire retina including the area under the electrode array remained well perfused. Similarly, histologic evaluation revealed near total preservation of the retina underlying the electrode array. CONCLUSIONS: Implantation of an electrode array on the epiretinal side (i.e., side closest to the ganglion cell layer) is surgically feasible, with insignificant damage to the underlying retina. The platinum and silicone arrays as well as the metal tacks are biocompatible. With the success of implanting an electrically inactive device onto the retinal surface for prolonged periods, the effects of long-term retinal electrical stimulation are now ready to be tested as the next step toward developing a prototype retinal prosthesis for human use.

Animals↗
PubMed1999

Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa.

PURPOSE: To evaluate the degree of inner retinal preservation in the extramacular regions of postmortem retinitis pigmentosa (RP) eyes. METHODS: Eighteen RP retinas and 11 age-matched healthy retinas were sectioned for morphometric analysis by light microscopy. The 18 RP retinas were classified by disease severity and mode of inheritance. Cell nuclei in the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL) were counted in adjacent 125-microm segments from an area spanning the region between 4 mm and 10 mm from the fovea. RESULTS: A mixed-effects model showed a decrease in mean cell counts for each of the cell layers when the severity groups and inheritance types compared with those of control retinas. There was no statistically significant difference in the number of nuclei preserved in the INL and GCL in the moderate group compared with the severe group. Results from the INL counts for the different inheritance types of RP showed a higher overall mean percentage of cells was preserved for the autosomal dominant RP (ADRP) group when compared with the X-linked (XLRP) and simplex RP groups. Analysis of the GCL counts revealed significantly more counts only in the ADRP group compared with the XLRP group; the other group comparisons were not significant. CONCLUSIONS: Retinitis pigmentosa results in cell loss in all retinal layers, with the most profound loss in the ONL, followed by the GCL and then the INL. The preservation of the INL and GCL in the extramacular region is less than that previously reported for the macular region of the same retinas.

Aged↗
PubMed1998

Artificial vision.

Outer retinal degenerations such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) lead to blindness because of photoreceptor degeneration. To test whether controlled electrical stimulation of the remaining retinal neurons could provide form vision, we electrically stimulated the inner retinal surface with micro-electrodes inserted through the sclera/eye wall of 14 of these patients (12 RP and 2 AMD). This procedure was performed in the operating room under local anaesthesia and all responses were recorded via a video camera mounted on the surgical microscope. Electrical stimulation of the inner retinal surface elicited visual perception of a spot of light (phosphene) in all subjects. This perception was retinotopically correct in 13 of 14 patients. In a resolution test in a subject with no light perception, the patient could resolve phosphenes at 1.75 degrees centre-to-centre distance (i.e. visual acuity compatible with mobility; Snellen visual acuity of 4/200).

Blindness↗
PubMed1997

Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis.

OBJECTIVE: To determine the extent of preservation in the inner retina in retinitis pigmentosa (RP). METHODS: We analyzed sectioned maculae of 21 postmortem eyes with RP and 19 age-matched, normal, postmortem eyes. Eyes were divided into 2 groups: severe and moderate RP. Cell nuclei were counted in the outer nuclear, inner nuclear, and ganglion cell layers within thirty 100-microns intervals from the foveola to 1500-microns eccentricity. RESULTS: Statistically significant (P < or = .05) loss of both the outer nuclear and ganglion cell layers was present in the groups with moderate and severe RP when compared with the control groups. However, even in the group with severe RP, 30% of the ganglion cells were histologically intact. Similarly, 78% and 88% of the inner nuclear layer cells were preserved in the groups with severe and moderate RP, respectively. Different inheritance modes showed no statistically significant differences in any of the retinal layers. CONCLUSIONS: Despite a statistically significant (P < or = .05) loss of cells found in all retinal layers, a large percentage of the inner retinal neurons remained histologically intact. Current experimental therapies, such as photoreceptor transplantation and implantation of a visual prosthesis, are based on the premise that some inner retinal neurons are preserved after death of photoreceptors in RP. Our observations support this assumption.

Aged↗
PubMed1996

Visual perception elicited by electrical stimulation of retina in blind humans.

OBJECTIVE: To evaluate the feasibility of bypassing damaged photoreceptors and electrically stimulating the remaining viable retinal layers to provide limited visual input to patients who are blind because of severe photoreceptor degeneration. METHODS: In the operating room with the patient under local anesthesia, focal electrical stimulation of the retinal surface with brief biphasic pulses was performed using small probes inserted through the sclera. The procedure was performed in five subjects who had little or no light perception. Three subjects had retinitis pigmentosa, one had age-related macular degeneration, and one had unspecified retinal degeneration from birth. RESULTS: Stimulation elicited visual perception of a spot of light (phosphene). Subjects who previously had useful vision accurately localized the phosphenes according to the retinal area stimulated. Two subjects could track the movement of the stimulating electrode by reporting movement of the elicited phosphene, and could perceive two simultaneous phosphenes on independent stimulation with two electrodes. In a resolution test, one of the subjects with no light perception in his left eye resolved phosphenes at 1.75 degrees center-to-center distance (ie, 4/200 OS visual acuity). CONCLUSIONS: Local electrical stimulation of the retinal surface in patients blind from outer retinal disease results in focal light perception that seems to arise from the stimulated area. Such findings in an acute experiment warrant further research into the possibility of prolonged retinal stimulation, improved resolution, and ultimately, an intraocular visual prosthesis.

Adult↗
PubMed1992

Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa.

There have been a number of histopathologic studies of retinas that were taken post mortem from patients with retinitis pigmentosa (RP), but few have addressed the question of transneuronal degeneration of ganglion cells secondary to photoreceptor death. We studied sectioned maculae that were obtained from 41 patients with different genetic forms of RP: autosomal dominant (n = 11); X-linked (n = 9); and simplex (n = 21). We also studied sectioned maculae that were taken from 20 age-matched normal subjects. We counted cell bodies in the photoreceptor and ganglion cell layers at 100-microns (0.35 degrees) intervals from the foveola to 1500-microns eccentricity and compared the mean cell counts among each group with RP. Each RP type had significantly fewer (P < .05) photoreceptors than those of the control group at each 100-microns interval. At eccentricities of 700 to 1500 microns, the retinas with X-linked and autosomal dominant RP had significantly fewer (P < .05) ganglion cells than those of the control group; the simplex RP mean ganglion cell counts were significantly lower (P < .05) than those of the control group, from 1000 to 1500 microns. The mean photoreceptor and ganglion cell counts had a .43 correlation (P < .001) in the zone of 700 to 1500 microns, consistent with transneuronal ganglion cell degeneration. Current experimental attempts to restore vision in diseased retinas by simulating or replacing photoreceptors are based on the premise that ganglion cells are retained after photoreceptor death. Our findings support this assumption.

Adolescent↗
PubMed1989

The rate of sulfur hexafluoride escape from a plastic syringe.

Sulfur hexafluoride (SF6) gas is widely used for internal tamponade during retinal reattachment surgery and is commonly injected into the eye from a 10-mL plastic syringe. The rate of diffusion of SF6 out of a plastic syringe has not bee studied. We measured the percentage of SF6 gas in a 10-mL plastic syringe by gas chromatography, confirmed by infrared spectrometry. Measurements were obtained immediately after aspiration, and at 30 s and 10, 15, 60, 90, and 120 minutes, and 18 hours. A marked decrease in SF6 concentration, from 97% at 30 s to 76% at 60 minutes and 2% at 18 hours, was noted. The results were highly reproducible. Sulfur hexafluoride gas should be injected into the patient's eye as soon as possible after aspiration from the tank to ensure accurate concentrations.

Chromatography, Gas↗
PubMed1989

Local cerebral glucose abnormalities in mild closed head injured patients with cognitive impairments.

Mild-moderate closed head injury (CHI) can be followed by neuropsychological impairments in recent memory and attention, despite the absence of discernible structural abnormalities in a significant number of patients. To determine whether CHI may result in cerebral glucose metabolic abnormalities, we used fluorodeoxyglucose (FDG) technique with PET imaging to measure local cerebral metabolic rates for glucose (LCMRGlu) in three CHI patients and three matched normal controls. The CHI patients were between 3-12 months post-injury. All had deficits in attention and recent memory shown by neuropsychological testing. CT, MRI, EEG and drug screens were negative at the time of PET scanning. Subjects were engaged in a vigilance task throughout the initial 30 min following FDG administration. Group comparisons were made using t tests. There were no significant group differences found in global glucose metabolic rate. Nevertheless, the CHI group exhibited significantly decreased LCMRGLu in medial temporal, posterior temporal, and posterior frontal cortices, as well as in the left caudate nucleus. LCMRGlu was significantly increased, relative to controls, in anterior temporal and anterior frontal cortices. These results suggest that CHI patients can have regional glucose metabolic abnormalities, indicative of altered neuronal function, despite the absence of discernible anatomic abnormalities.

Brain↗
PubMed1989

Histopathology of experimental preretinal neovascularization.

Despite the morbidity resulting from abnormal retinal neovascularization, morphological events associated with its development have not been fully described. We therefore studied sequential morphologic events during preretinal neovascularization in an experimental model induced by injection of 250,000 homologous fibroblasts into the vitreous cavity of rabbits. Within 2 days following fibroblast injection, thickening of many venular and capillary endothelial cells resulted in partial obliteration of their lumina. 3H-thymidine incorporation occurred first in the nonvascular cells of the superficial medullary ray and thereafter in the preretinal vessels and extraretinal fibroblasts. Capillary budding was obvious within 3 days, with endothelial cells extending cytoplasmic processes into fragmented extracellular matrix (ECM). Endothelial cells, at the tips of budding vessels, and at more proximal sites in the parent vessel, incorporated 3H-thymidine and did not lose cell contact or migrate individually into the ECM. Lumina were present throughout the entire length of the buds and endothelial cells remained polarized. Neovascular events observed in this experimental model parallel those previously described in diabetic retinopathy and retinopathy of prematurity in humans.

Animals↗