Biomedical subjects

D Munguia

Publications and source records attributed to D Munguia.

34 records · Page 2Linked to original sources

PubMed1995

Evaluation of retinal toxicity of acetylcholine in rabbit eyes.

PURPOSE: In vitreoretinal surgery, pupillary constriction may be required at the termination of a procedure especially if mechanical pupillary dilation was used in eyes filled with gas or silicone oil. A miotic agent instilled into the anterior chamber will sink and come into direct contact with retina in the aphakic or pseudophakic vitrectomized eye. Therefore, the retinal toxicity of acetylcholine, a miotic used for pupillary constriction, was studied. METHODS: Eight Dutch pigmented rabbit eyes were vitrectomized, had air-fluid exchange, and were injected with a 20% mixture of SF6. Subsequently eyes were randomly selected to have injections of 0.75 ml of 10 mg/ml acetylcholine (Miochol, Iolab Corp., Claremont CA) versus 0.75 ml of lactated Ringer's solution. Short-term (2 weeks) and long-term (6 weeks) retinal toxicity was assessed by ophthalmoscopy, electroretinogram, and histology by light and electron microscopy at both times. RESULTS: Ophthalmoscopy, electroretinographic tracings, histology, and electron microscopy disclosed no significant abnormalities. CONCLUSIONS: Acetylcholine does not appear to have significant retinal toxicity even when undiluted solutions are in direct contact with the retina. We therefore postulate that intraoperative use of acetylcholine in previously vitrectomized eyes filled with gas or silicone is safe.

Acetylcholine↗

PubMed1995

Antiviral effect in human cytomegalovirus-infected cells, pharmacokinetics, and intravitreal toxicology in rabbits of acyclovir diphosphate dimyristoylglycerol.

Acyclovir diphosphate dimyristoylglycerol (ACVDP-DG) is a lipid prodrug which is active against ACV-resistant strains of herpes simplex virus because of its intracellular metabolism to ACV monophosphate. In human cytomegalovirus (HCMV)-infected MRC-5 cells, ACVDP-DG was ninefold more active than ACV. When liposomal [8-3H]ACVDP-DG was injected intravitreally at the maximum nontoxic dose of 1 mumol in rabbits, the drug remained above its estimated 90% HCMV-inhibitory concentration for 18 days. Intravitreal ganciclovir persists above its 90% inhibitory concentration for only 1 to 2 days. ACVDP-DG may be useful as a local treatment for HCMV retinitis.

Acyclovir↗

PubMed1995

Evaluation of retinal toxicity and efficacy of the anticytomegalovirus compound 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine.

Compound 2242, also known as 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine, is the first known antivirally active nucleoside analog with the side chain substituted at the N-7 position of the purine ring system. Our purpose was to evaluate its retinal toxicity and assess the efficacy of its highest nontoxic concentration in a rabbit model of herpes simplex retinitis. Concentrations of the drug from 0.5 to 2,000 microM were injected intravitreally in twelve New Zealand White rabbits. Fundoscopic, histologic, and electrophysiologic data revealed no evidence of toxicity even at the highest dose of the compound. Dutch pigmented rabbits (n = 34) had their left eyes injected with herpes simplex virus type 1 3 days after, concurrently, or 3 days before intravitreal injection of either 2,000 microM compound 2242 or 480 microM ganciclovir (final concentration in the eye). Both compound 2242 and ganciclovir were equally effective compared with saline when administered simultaneously with the virus (P < 0.0001). In the 3-day pretreatment paradigm, compound 2242 was superior to ganciclovir (P < 0.04), but there was no clear difference between the two with regard to their effects on an established infection. The pharmacokinetics of compound 2242 in 10 rabbits injected intravitreally with 30 microM showed an intravitreal half-life of 8 h. This compound, which may be orally active in its pro form, has a very high therapeutic index in the eye and is more efficient than ganciclovir in this animal model of herpes retinitis.

Administration, Oral↗

PubMed1995

Intraocular tolerance of perfluorooctylbromide (perflubron)

PURPOSE: To determine the intraocular tolerance of perfluorooctylbromide (perflubron) in vitrectomized rabbit and pig eyes and evaluated its use as a vitreous substitute in virteoretinal surgery. METHODS: Pars plana vitrectomy was performed on 33 Dutch pigmented rabbits and 11 micro mini pigs. After vitrectomy the eyes were filled with perflubron for 2 hours, 1 week, 2 weeks, 1 month, and up to 6 months. RESULTS: No clinical, electroretinographic, or light and electron microscopic evidence of adverse effects on the retina and lens were observed. Perflubron emulsified and dispersed into small bubbles after 2-3 weeks. The lens showed mild posterior subcapsular cataracts in pig eyes after long-term retention of perflubron. CONCLUSION: These findings indicate that perflubron is safe for intraoperative and for long-term use intravitreally. However, emulsification and the breakdown into small bubbles limits the view of the retina when perflubron is used as a long-term tamponade.

Animals↗

PubMed1994

Macular serous exudation in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.

Central visual loss in cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS) occurs in two forms: direct macular tissue destruction and secondary involvement as part of rhegmatogenous retinal detachment. We treated 32 patients (35 eyes) with macular exudation that caused reversible visual loss and initially manifested as neurosensory retinal detachment and lipid exudates. Of 35 eyes, 25 showed papillary or peripapillary active retinitis and ten showed retinitis 1,500 to 3,000 microns from the fovea. Of 23 eyes with reduced vision that were followed up until healing of the retinitis and resolution of subretinal fluid and lipid exudates, 22 (96%) showed visual improvement with anti-cytomegalovirus treatment. Our findings suggest that macular exudation is a reversible cause of visual loss in patients with cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗

PubMed1994

A masked prospective evaluation of outcome parameters for cytomegalovirus-related retinal detachment surgery in patients with acquired immune deficiency syndrome.

PURPOSE: The management of cytomegalovirus (CMV)-related rhegmatogenous retinal detachments in patients with acquired immune deficiency syndrome (AIDS) has been the subject of recent attention and controversy because of the high degree of variability in visual outcome, as well as significant differences in the reported incidence of profound postoperative optic atrophy. This study was designed to evaluate the various parameters affecting postoperative visual outcome, and to quantitate the degree of postoperative optic disc pallor. METHODS: The results of 65 consecutive surgeries for CMV-related retinal detachments in 51 patients with AIDS were prospectively studied. Postoperative vision, survival, optic disc pallor, and retinitis extent were analyzed. Serial photographs of optic discs underwent masked evaluation. RESULTS: Mean postoperative survival was 30 weeks (range, 2-146 weeks). Mean best postoperative visual acuity was 20/66 (range, 20/20-2/200) and mean final postoperative visual acuity was 20/100 (range, 20/25-no light perception). Analysis of visual outcome for eyes with no macular or papillo-macular retinitis showed a best postoperative visual acuity of 20/60 (range, 20/25-2/200) and mean final postoperative visual acuity of 20/80 (range, 20/25-no light perception). Postoperative vision was not affected by the presence of a preoperative macular detachment, with both groups (macula on or off detachments), achieving a best postoperative visual acuity of 20/60 in the absence of macular retinitis. Mild postoperative optic disc pallor was observed in 30% of surgical eyes at the final postoperative visit, and moderate pallor was noted in 13%. The mean degree of optic disc pallor was not different from the degree of optic disc pallor seen in fellow, nonsurgical eyes with CMV retinitis (surgical versus fellow nonsurgical eyes, 29% +/- 23% versus 26% +/- 30%; P = 0.64). CONCLUSION: In this largest reported series of reattachment surgery for CMV-related retinal detachments, patients are experiencing increased postoperative survival, good vision, and relative optic nerve health.

AIDS-Related Opportunistic Infections↗

PubMed1994

Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), a high-potency antiherpes and anticytomegalovirus (CMV) drug was evaluated in the treatment of experimental retinitis caused by preretinal herpes simplex virus (HSV-1) injection in rabbits. HPMPC (100 micrograms/0.1 mL) was intravitreally injected 10, 15, 21, 30, or 46 days before, concurrently, or 3, 5, or 7 days after viral inoculation. Ganciclovir (200 micrograms/0.1 mL) was intravitreally injected 3, 7, or 10 days before HSV-1 inoculation, concurrent with viral inoculation, or 3, 5, or 7 days after viral inoculation. Eyes pretreated with HPMPC were protected from retinitis for 15-21 days. Ganciclovir did not protect completely even if administered 3 days before inoculation. Early treatment of established retinitis with HPMPC markedly delayed the progression of the infection. However, with ganciclovir there was delayed progression only in rabbits treated 3 days after viral inoculation. HPMPC had a remarkably potent and prolonged (< or = 1 month) antiviral effect in this retinitis model and may prove more useful than ganciclovir in local treatment of CMV retinitis.

Animals↗

PubMed1994

Retinal toxicity of the antimetabolite 5-fluorouridine 5'-monophosphate administered intravitreally using multivesicular liposomes.

BACKGROUND: Liposome-encapsulated 5-fluorouridine-5'-monophosphate (FUMP) has been shown to inhibit proliferative vitreoretinopathy in a rabbit model. Liposome encapsulation extends the intravitreal half-life of this antiproliferative drug by a factor of 28 times. METHODS: The current study investigated the retinal toxicity of intravitreal injections of 10, 50, and 100 micrograms FUMP as free drug or within liposomes in rabbits. Evaluation included ophthalmoscopic examination, electroretinography, and histologic analysis by light and electron microscopy. RESULTS: No electroretinographic evidence for toxicity of FUMP was found. Light and electron microscopy showed only mild transient vacuolization in the outer segment layer, without inflammation. Empty liposomes incurred no toxic effects on the retina. CONCLUSIONS: Our results suggest that liposome-encapsulated FUMP may be non-toxic to the retina at doses that inhibit proliferative retinopathy.

Animals↗

PubMed1993

Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis.

We studied 259 patients to determine the time-dependent risk and risk factors for the development of retinal detachment in patients with cytomegalovirus retinitis. The six-month and one-year retinal detachment rates (by eye) were 11% and 24%, respectively. Increasing retinal surface involvement outside of the posterior pole and the presence of retinitis activity were found to be the two covariates that best predicted retinal detachment. Eyes with peripheral involvement greater than 25% had a fivefold risk for detachment, compared to eyes with 10% involvement. If there was retinitis activity and more than 25% peripheral (external to major vascular arcades) involvement, the risk increased to 24-fold. The presence of a fellow eye with retinal detachment was not an independent risk factor. These observations should help in the design of a prophylactic trial intended to prevent retinal detachment and should also help ophthalmologists counsel patients with cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗

PubMed1993

An animal model of focal, subacute, viral retinitis.

To study local intravitreal therapies for retinitis due to herpes viruses, an animal model of focal, subacute, relatively nonlethal herpes family retinitis is needed. Herpes simplex virus type 1 (HSV-1) was injected into the subretinal space of 33 Dutch pigmented rabbit eyes. The animals were observed for up to 42 days after the inoculation. All inoculated eyes developed a focal, enlarging area of retinitis in a predictable manner, showing focal enlarging areas of retinal opacification and necrosis with variable retinal hemorrhage. In the inoculated eyes, retinal detachment developed in all animals within 21 days; 33% of the animals developed focal retinitis in the uninoculated eye. Histologic examination showed encephalitis to be present in 11 (73%) of the 15 animals studied after 1 week. This model may be used to evaluate the therapeutic efficacy of new antiviral agents and modalities in the treatment of herpes family viral retinitis. The model is most similar to herpes simplex or zoster retinitis in humans, but also shares some similarities (and differences) with cytomegalovirus (CMV) retinitis in humans.

Acute Disease↗

PubMed1993

Evaluation of retinal toxicity and liposome encapsulation of the anti-CMV drug 2'-nor-cyclic GMP.

PURPOSE: Human cytomegalovirus (HCMV) is an important pathogen in the immunocompromised patient. CMV retinitis is a leading cause of blindness in patients with AIDS. Ganciclovir and foscarnet are currently the treatments being used for this retinitis, but they both have major toxicities when used systemically. Intravitreal therapy with ganciclovir has been used in some patients who cannot tolerate systemic treatment. The major problem with this modality is the necessity for administration of between 1 and 3 intravitreal injections per eye per week. 2'-nor-cyclic GMP is a nucleotide analog, a cyclic phosphate derivative of ganciclovir. Neutral salts of the compound are extremely water soluble, and the charged phosphate group at neutral pH make it an ideal candidate for encapsulation into a multivesicular liposome system. METHODS: The authors evaluated the retinal toxicity of the diethanolammonium salt 2'-nor-cyclic GMP by using electroretinographic, morphologic, and ophthalmoscopic techniques after intravitreal injections in rabbit eye. RESULTS: The intraocular therapeutic index for 2'-nor-cyclic GMP is 20. At the 10 micrograms dose, electroretinogram, ophthalmoscopic examination, and both light and electron microscopy revealed no abnormalities. Toxicity was evident at 50 micrograms and higher doses with ERG changes (loss of amplitude) and retinal pathology that varied from vacuolization of the retinal pigment epithelium and loss of height of the outer photoreceptor segment to loss of the entire outer retina. In addition, an in vitro drug release half-life of 1,000 hours (more than 75 times that of ganciclovir) was found for 2'-nor-cyclic GMP in liposome, which may be able to be exploited in the therapy of patients with CMV retinitis unable to tolerate toxic systemic therapy. CONCLUSION: The anti-CMV drug, 2'-nor-cyclic GMP, may be promising for intravitreal injection, particularly if encapsulated into liposomes.

Animals↗

PubMed1992

Visual dysfunction without retinitis in patients with acquired immunodeficiency syndrome.

Patients with human immunodeficiency virus infection may have noninfectious and infectious retinopathies, as well as clinical symptoms consistent with optic nerve dysfunction. Noninfectious acquired immunodeficiency syndrome-related retinopathy is seen in most patients with AIDS. Morphologic studies have shown that the number of retrobulbar optic nerve fibers in patients with AIDS is decreased compared to the number of optic nerve fibers in normal control eyes. To determine whether these patients had a visual dysfunction consistent with damage to the macula and optic nerve, 78 subjects (156 eyes) were studied using color-vision and contrast-sensitivity testing. The Farnsworth-Munsell 100-Hue color-vision test was performed on all subjects and age-corrected color-vision scores for all groups were compared. A significant decrease in color discrimination was found in the patients with AIDS (P less than .001). Contrast-sensitivity testing disclosed a deficit of contrast threshold in patients with AIDS at four of five spatial frequencies and in patients with AIDS-related complex at three of the five spatial frequencies examined. This study demonstrated a functional visual deficit in eyes without retinitis consistent with dysfunction of the macula or optic nerve in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1992

The prethreaded pupillary dilating (torpedo) suture for phakic and aphakic eyes.

A variety of methods for maintaining pupillary dilation for intraocular surgery have been advocated because pharmacologic agents may fail to maintain or adequately dilate the pupil. We have used a threaded needle to rapidly dilate the pupils of 19 aphakic, pseudophakic, or phakic eyes without damaging the lens or pseudophakos. This dilating suture can be constructed from available materials at low cost. We discuss the preparation of the suture and the techniques that allow rapid and reliable dilation during posterior vitrectomy or anterior segment surgery. Histologic studies were performed on rabbit eyes and demonstrated the position of the suture after performing pupillary dilation in phakic eyes. The technique has been used to dilate the pupils of phakic, aphakic, and pseudophakic patients without evidence of clinically significant complications.

Animals↗

PubMed1992

Surgical repair of rhegmatogenous retinal detachment in immunosuppressed patients with cytomegalovirus retinitis.

The authors performed retinal reattachment surgery in 29 eyes of 24 patients with acquired immune deficiency syndrome virus with retinal detachment associated with cytomegalovirus (CMV) retinitis and documented the course of eight additional untreated eyes. Retinal detachment repair using vitrectomy, posterior hyaloid removal, and intraocular tamponade with silicone oil or SF-6 gas resulted in a total retinal reattachment rate of 76% and a macular attachment rate of 90% in one operation. The mean postoperative visual acuity (best corrected) was 20/60, but, in some patients, the visual acuity decreased because of progressive retinitis. Prophylactic laser photocoagulation of fellow eyes to surround CMV lesions did not appear to prevent retinal detachment. The mean postoperative survival was 37 weeks (range, 8 to 127 weeks). The surgical techniques used and pathophysiology of these retinal detachments are discussed.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Lack of retinal toxicity of the anticytomegalovirus drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine.

The drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC) is an antiherpesvirus group compound with a higher potency and longer duration of action against human cytomegalovirus (CMV) than ganciclovir or foscarnet. Twenty eyes of ten New Zealand white rabbits received 0.1-ml injections of either normal saline or HPMPC at doses of 10, 50, 100, 300, or 1000 micrograms. The animals were killed on days 14 and 28. Toxicity was assessed by indirect ophthalmoscopy, electroretinography (ERG), and light and electron microscopy. Both a- and b-wave ERG findings and indirect ophthalmoscopic appearance of retinas in all groups were normal. Light and electron microscopy of perfusion-fixed retinal tissue revealed no morphologic changes at doses of 100 micrograms or lower. The pharmacokinetics of eight rabbits injected intravitreally with 100 micrograms of HPMPC showed a 24.4-hr half-life for the drug. These results indicate that HPMPC is not toxic to the rabbit retina at 500-1000-fold the dose that is effective in suppressing CMV infections. Doses of 100 micrograms also were injected into the vitreous of monkey eyes. Intravitreal injections of HPMPC may be efficacious in inhibiting CMV retinitis for longer dosing intervals than can be used with other anti-CMV compounds.

Animals↗

PubMed1990

Longitudinal study of cytomegalovirus retinitis in acquired immune deficiency syndrome.

The authors prospectively evaluated 67 consecutive patients with the acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis during a 33-month period to assess the clinical patterns of retinal infection, efficacy of treatment, long-term survival, and relationship of retinitis to immune function. Immediately sight-threatening retinitis presented in six patients (9%) with peripapillary disease; primary foveal infection was not observed. Eighty-seven percent of patients were treated with ganciclovir. Thirty-nine patients (58%) presented with unilateral disease and contralateral infection developed in 15% of those while on ganciclovir. Smoldering (incompletely responsive) retinitis was seen in 33% of the 21 patients whose retinitis progressed while receiving ganciclovir. Progression of treated retinitis was associated with a lower lymphocyte count (P = 0.04). Median survival after diagnosis of CMV retinitis was 8 months. This represents the largest reported prospective study of CMV retinitis and indicates that (1) CMV infrequently poses an immediate threat to vision on presentation, (2) response to therapy may be related to immune function, and (3) smoldering retinitis should be recognized as an important clinical entity associated with treatment failure.

Acquired Immunodeficiency Syndrome↗