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Reducing chorioretinal viral counts with intravitreal foscarnet injections in a rabbit model of Herpes simplex virus type-1 retinitis.

The efficacy of intravitreal foscarnet injections was evaluated in a rabbit model of Herpes simplex virus type-1 (HSV-1) retinitis. In untreated infected animals, viral titration revealed that the optic chiasm, vitreous and chorioretina were positive for HSV-1. On the other hand, foscarnet treatment significantly decreased the viral count in the chorioretina when compared to the untreated group. Immunolocalization of HSV in untreated infected animals clearly showed infected cells in the outer and inner layers of the retina and also in the ciliary body of the eye. Clinical examination by indirect ophthalmoscopy indicated an absence of optic nerve congestion and a lower level of vitritis in foscarnet treated animals compared to the untreated group. It is concluded that intravitreal injections of foscarnet reduced the viral titer in the chorioretina in a rabbit model of HSV-1 retinitis. This route of administration might be valuable for the treatment of CMV retinitis in AIDS patients with sight threatening lesions or intolerance to intravenous anti-CMV drugs.

Administration, Topical↗

Ocular toxicity of intravitreal indocyanine green.

We report 6 cases of indocyanine green (ICG)-related ocular toxicity after intravitreal ICG usage. Five cases had preoperative diagnosis of macular hole, 1 case had preoperative rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy. All cases received vitrectomy, ICG-assisted internal limiting membrane (ILM) peeling and air-fluid exchange. All eyes had residual ICG left at the end of surgery. Patients were followed up with indirect ophthalmoscopy, visual acuity, color fundus photography, fluorescein angiography, and ocular coherence tomography. Circular foveal retinal pigment epithelium atrophy larger than the area of macular hole and surrounding cuff was noted in 4 of 5 cases with preoperative macular hole. The other eye with preoperative diagnosis of macular hole had shallow anterior chamber and low intraocular pressure lasting for 1 week postoperatively. Diffuse retinal pigment epithelial atrophy was noted in the eye with preoperative proliferative vitreoretinopathy. Four eyes demonstrated optic atrophy postoperatively. Ocular toxicity caused by ICG may present as pigment epithelial atrophy, which is characteristically larger than the previous area of macular hole and surrounding cuff. Disc atrophy, retinal toxicity, and ocular hypotony were also observed in some cases. To prevent toxicity, residual ICG and ICG-stained ILM must be removed as completely as possible.

Aged↗

Incidence and progression of diabetic retinopathy among non-insulin-dependent diabetic subjects: a 4-year follow-up.

BACKGROUND: To assess the incidence and progression of diabetic retinopathy and explore risk factors associated with them among non-insulin-dependent diabetes mellitus (NIDDM) patients. METHODS: A total of 471 NIDDM subjects aged > or 40 were recruited from four primary health care centres of northern Taiwan in 1986 and followed up for 4 years. Their ocular fundi were clearly visible by ophthalmoscopy and the status of diabetic retinopathy could be graded. A structured questionnaire interview was conducted to collect basic data. Overnight fasting venous blood was collected every year to measure the levels of glucose, glycosylated haemoglobin (HbA1c), cholesterol and high density lipoprotein cholesterol. RESULTS: Among the 344 subjects who had no retinopathy initially, 66 subjects developed retinopathy 4 years later giving a 4-year cumulative incidence of 19.2%. Of the 120 subjects initially with background or preproliferative retinopathy, evidence of deterioration developed in 36 subjects. The cumulative incidence of progression was 30%. Seven subjects developed proliferative retinopathy giving a cumulative incidence of progression to proliferative retinopathy of 5.8%. The univariate analysis disclosed that the development of retinopathy was correlated with mean fasting blood glucose (MFBG) and HbA1c, diabetic duration, diabetic treatment and residential area. The progression of retinopathy correlated with MFBG and proteinuria, and the progression to proliferative retinopathy correlated with MFBG. Stepwise logistic regression analysis revealed that MFBG and HbA1c were the significant risk factors related to the development of retinopathy. CONCLUSIONS: Diabetic control assessed by MFBG or HbA1c was the significant risk factor correlated with the incidence and progression of retinopathy.

Adult↗

Aerobic bacterial conjunctival flora in diabetic patients.

OBJECTIVE: To study the aerobic conjunctival flora of diabetic patients and its relation to the presence and level of diabetic retinopathy and the duration of the disease. METHODS: One hundred three patients from the diabetic retinopathy screening program of the Federal University of São Paulo with no evidence of ocular surface disease were included. The diabetic patient cohort was compared with 60 nondiabetic subjects. All patients underwent slit-lamp evaluation, conjunctival scrapings, and indirect ophthalmoscopy. RESULTS: The frequency of positive conjunctival cultures was significantly higher in the diabetic group (94.18%) than in the nondiabetic group (73.33%). Among diabetic patients, a significantly higher frequency of positive cultures was detected in those with diabetic retinopathy than in those without retinopathy. Neither the duration of the diabetes nor the hypoglycemic therapy correlated with the culture results. Coagulase-negative Staphylococcus was the most common microorganism isolated, and its identification was more frequent in patients with retinopathy than in those without diabetic retinopathy. CONCLUSION: Diabetic patients have a significantly higher number of positive conjunctival cultures. The presence of diabetic retinopathy was correlated with an increase in positive cultures and a higher proportion of coagulase-negative Staphylococcus.

Aged↗

Cost-effectiveness of strategies for detecting diabetic retinopathy.

A computer model has been developed to determine cost-effectiveness of screening and treatment for diabetic retinopathy from a societal viewpoint. This model was used to evaluate biannual and annual screening programs using ophthalmoscopy, fundus photography with a "nonmydriatic camera," and photography with a "mydriatic camera." Computations were performed for three subpopulations formed by patients with younger onset diabetes (age at diagnosis less than 30 years) of 5 years or more duration, with older onset diabetes (age at diagnosis greater than or equal to 30 years) who are taking insulin, and with older onset diabetes not taking insulin. Population characteristics are from a well-described southern Wisconsin population where data are available, but the computer model may be specialized to other population. Generally costs of screening programs appear to be recovered by avoided costs of blindness in the population subgroups taking insulin; however, the cost of screening programs generally are not recovered by avoiding costs of blindness in the older onset population subgroup not taking insulin. It was estimated that supplying annual examination with mydriatic fundus photography as a screening program to a cohort of 1,000 diabetics from the younger onset population who have been diagnosed at least 5 years and who are currently not receiving care might save 319 sight years over the lifetime of the cohort. This program will save 62 sight years in an older onset cohort who are taking insulin, and 21 sight years in the older onset population not taking insulin (all benefits are presented as present values computed with an annual discount rate of 5%). Other programs achieve slightly lower savings in each subpopulation.

Adult↗

Interexaminer reliability of the optic cup to disc ratio assessment.

Previous controlled reliability studies of cup to disc (C/D) ratio estimations may have been biased by lack of criteria for cup determination, small sample size; and/or large interval grouping of collected data. In our study four examiners independently estimated the C/D ratios of 40 patients by direct ophthalmoscopy using a contour criterion for cup determination. Results indicated that 75% of the estimate pairs differed by 0.10 or less. Fewer than 14% of the estimate pairs differed by 0.2 or greater. The results of the study suggest that when examiners use a specified criterion of contour cupping, interexaminer assessment of the C/D ratio estimation is clinically and statistically reliable.

Adolescent↗

Monocular vs. stereoscopic measurement of cup-to-disc ratios.

Stereoscopic viewing of the optic nerve head and cup has been reported to provide more reliable cup-to-disc (C/D) ratio estimates. We investigated the variability in C/D ratio estimates among three experienced optometric clinicians using conventional direct ophthalmoscopy and indirect biomicroscopy with the Volk 90 D lens. The pupils of 21 subjects were dilated and the discs assessed randomly by each examiner for the determination of the C/D ratio. Analysis of variance indicates that the two methods are not significantly different from each other when comparing interexaminer reliability. However, for a particular examiner, one method may be more effective than the other.

Adult↗

Indocyanine green angiographic aspects of multiple evanescent white dot syndrome.

PURPOSE: The authors investigated the indocyanine green angiography findings of multiple evanescent white dot syndrome (MEWDS). METHODS: Four patients with MEWDS underwent examination by indocyanine green angiography, conventional ophthalmoscopy, and fluorescein angiography. RESULTS: Fundus examination showed multiple white dots in the retinal pigment epithelium of the unilateral eye of each patient. Fluorescein angiography demonstrated early hyperfluorescence corresponding to the white dots. In the early phase, indocyanine green angiography showed no abnormal signs in the large choroidal vessels, but in the late phase, hypofluorescent lesions appeared, corresponding to the white dots. The hypofluorescent dots were clustered in the posterior pole and sporadic in the peripheral region, appearing to radiate away from the optic disc or fovea. The hypofluorescent dots disappeared at the recovery stage. CONCLUSIONS: Previous fluorescein angiographic and electrophysiologic studies have demonstrated the involvement of the retinal pigment epithelium (RPE) and photoreceptors in MEWDS: The current findings on indocyanine green angiography suggest that MEWDS affects the choriocapillaris or precapillary arterioles as well as the RPE and photoreceptors, and that the lesions spread to the midperipheral region, centering on the optic disc or fovea.

Adult↗

Subretinal bleeding without choroidal neovascularization in pathologic myopia. A sign of new lacquer crack formation.

PURPOSE: The clinical significance of subretinal bleeding without choroidal neovascularization in pathologic myopia is unclear. Only two reports in the ophthalmic literature have demonstrated the clinical course of subretinal bleeding and have indicated that it might be a precursor of lacquer cracks. In this study, the authors observed the clinical course of subretinal bleeding in highly myopic eyes and studied this condition in relation to new lacquer crack formation. METHODS: The authors examined consecutively and prospectively 22 highly myopic eyes (19 patients) with subretinal bleeding. Indirect ophthalmoscopy and fluorescein fundus angiography were performed in all patients. Indocyanine green (ICG) angiography could be performed in three patients. The follow-up period ranged from 6 to 198 months (mean, 61.3 months). RESULTS: In 17 of 22 eyes, lacquer cracks appeared at the site of previous subretinal bleeding. The period for the formation of new lacquer cracks after the onset of the bleeding ranged from 2 to 6 months (mean, 4.0 months). In one patient, ICG angiography revealed linear hypofluorescence, indicating a ruptured Bruch's membrane at the onset of subretinal bleeding. CONCLUSION: A rupture of Bruch's membrane and choriocapillaris complex results in subretinal bleeding, which is the first process of new lacquer crack formation. Atrophy of the overlying pigment epithelium and further scar formation results in the development of a lacquer crack.

Adolescent↗

Timing of dexamethasone treatment in experimental Staphylococcus aureus endophthalmitis.

PURPOSE: This study sought to determine whether intravitreal dexamethasone with vancomycin preserves retinal function in eyes with experimental Staphylococcus aureus endophthalmitis better than intravitreal vancomycin alone. METHODS: Twenty-four rabbits received intravitreal injections in both eyes with S. aureus. Right eyes were treated with intravitreal dexamethasone plus vancomycin and left eyes were treated with vancomycin alone at 24, 36, 48, or 72 hours after inoculation. Evaluation was performed by slit-lamp biomicroscopy, indirect ophthalmoscopy, and electroretinogram. Vitreous humor cultures and histopathologic examinations were performed on the eyes after the rabbits were killed. RESULTS: The combination of intravitreal dexamethasone and vancomycin resulted in significantly less inflammation than vancomycin alone at 24 and 36 hours after inoculation, but electroretinograms showed significantly better preservation only at 36 hours after bacterial inoculation. Viable bacteria were cultured from eyes treated 48 and 72 hours after inoculation. CONCLUSION: Intravitreal dexamethasone was found to be beneficial by electroretinography when administered 36 hours after infection. In the authors' model, a single intravitreal injection of vancomycin with or without the addition of dexamethasone was insufficient to sterilize eyes 48 and 72 hours after bacterial inoculation.

Animals↗

Safety of repeated intravitreous injections of antibiotics and dexamethasone.

PURPOSE: To determine the retinotoxicity of repeated intravitreous injections of vancomycin, ceftazidime, and dexamethasone in rabbit eyes. METHODS: Twenty pigmented New Zealand rabbits were divided into two groups. In Group 1, the right eyes received repeated intravitreous injections with vancomycin 0.3 mg, ceftazidime 0.7 mg, and dexamethasone sodium phosphate 0.13 mg at three consecutive 48-hour intervals. Group 2 right eyes received three times higher dose of the same intravitreous drugs as used in Group 1, repeated at the same frequency. All left eyes served as control eyes. Retinotoxicity was monitored by slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy. RESULTS: No evidence of retinotoxicity was found in Group 1 eyes. Photopic A-waves were significantly elevated, and 30- and 50-Hz flicker fusion amplitudes were significantly depressed in Group 2 eyes. No changes were found by clinical or histopathologic examination in the retinas of either group. CONCLUSIONS: Three repeated intravitreous injections at 48-hour intervals of a combination of vancomycin, ceftazidime, and dexamethasone in rabbit eyes at dosages that approximate drug concentrations recommended for human endophthalmitis were nontoxic. Similar injections at three times higher doses resulted in mild electroretinogram changes.

Animals↗

Choroidopathy in patients with sarcoidosis observed by simultaneous indocyanine green and fluorescein angiography.

PURPOSE: To examine choroidopathy in patients with sarcoidosis. METHODS: In a prospective clinical study, 10 consecutive patients (20 eyes) with sarcoidosis underwent simultaneous indocyanine green (ICG) and fluorescein angiography (FA) with a double detector of scanning laser ophthalmoscopy. Angiographic findings recorded on videotapes were evaluated, and the relation of ICG angiographic findings with systemic activity and the extent of retinal inflammation was analyzed. RESULTS: Indocyanine green angiographic findings, not evident with fluorescein, were multiple lobular hypofluorescent spots in the posterior pole in 10 eyes of 5 patients, isolated hypofluorescent plaques in 2 eyes of 1 patient, hyperfluorescent spots in 3 eyes of 2 patients, and segmental choroidal vascular wall staining in 6 eyes of 4 patients. The multiple lobular hypofluorescent spots with ICG were observed at a significantly higher rate in eyes with extensive retinal vascular leakage of fluorescein than in eyes with minimal leakage (chi-square test, P = 0.0007). CONCLUSIONS: The patients with sarcoidosis showed choroidal abnormalities that could be revealed by ICG angiography, but not by funduscopy or FA. Simultaneous ICG and FA angiography may be useful for examining choroidal lesions in sarcoidosis.

Adult↗

Optical coherence tomography findings in the macula after treatment of rhegmatogenous retinal detachments with spared macula preoperatively.

PURPOSE: To present the postoperative optical coherence tomography (OCT) findings of the macula in rhegmatogenous retinal detachment with spared macula preoperatively. METHODS: Eleven of 46 patients who underwent surgery for rhegmatogenous retinal detachment had an uninvolved macula preoperatively. Scleral buckling without intravitreous gas injection was the operation used in all eyes. All 11 patients were examined before and after treatment with slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, fluorescein angiography, and OCT. RESULTS: In 3 of the 11 patients with rhegmatogenous retinal detachment and uninvolved macula preoperatively, fluid was identified with OCT in the macula after successful treatment. OCT showed that the fluid gradually diminished and finally disappeared 5 to 7 months after the scleral buckling procedure. The fluid in the macula became visible with slit-lamp biomicroscopy in only one of the three patients. CONCLUSION: Subretinal fluid in a preoperatively uninvolved macula can be found after successful treatment of rhegmatogenous retinal detachment. If the fluid is located in the fovea, the visual acuity decreases and does not reach the preoperative levels. OCT identifies the presence of fluid and contributes to the study of the fluid's evolution.

Adult↗

Optical coherence tomography of branch retinal vein occlusion.

PURPOSE: To evaluate the incidence of serous retinal detachment (SRD) secondary to a branch retinal vein occlusion (BRVO) by using optical coherence tomography (OCT). METHODS: Fourteen eyes of 14 patients with a BRVO underwent a detailed history, ophthalmoscopic examination, and fluorescein angiographic evaluation. They were also studied with OCT. RESULTS: The 14 patients included eight women and six men with a mean age of 73.6 +/- 10.5 years (range, 55-90 years). Four eyes were found to have cystoid macular edema by fluorescein angiography, whereas 10 cases were detected by OCT. SRD involving any portion of the macula was found in 10 (71.4%) of the 14 eyes, and SRD extending into the fovea was found in six (42.9%) eyes. Two (14.3%) of the 14 patients also showed a subfoveal hemorrhage that appeared to have gravitated inferiorly through the SRD to the dependent portion of the detachment. CONCLUSIONS: That few patients with SRD secondary to a BRVO discovered by ophthalmoscopy have been reported in the literature would suggest that this is an uncommon complication. The authors found with OCT that SRD commonly occurs in BRVO. In addition, subretinal hemorrhage may occur in the context of BRVO, and the authors propose that blood gravitates through the subretinal fluid to settle behind the retina.

Aged↗

Acute exudative polymorphous vitelliform maculopathy syndrome.

PURPOSE: The authors describe clinical characteristics of acute exudative polymorphous vitelliform maculopathy syndrome, also termed polymorphous maculopathy syndrome (PMS), an unusual tapetoretinal disorder first reported by Gass. METHODS: Detailed ophthalmoscopy, fluorescein angiography, electrophysiology, and optical coherence tomography (OCT) were performed on a patient with PMS. RESULTS: Numerous small, yellowish lesions arranged in a honeycombed pattern at the level of the retinal pigment epithelium (RPE) around the disk and the macula, a shallow macular detachment (documented by OCT), and a perifoveolar yellow ring appeared in both eyes. Initial fluorescein angiography revealed mild early hyperfluorescence and late staining of the perifoveolar rings and the multifocal yellow lesions. Gradually, subretinal yellowish deposits gravitated as a meniscus below the macula with subsequent further changes. Electrophysiology showed reduced amplitudes of the electroretinogram and electrooculogram and abnormal dark adaptometry. A rhegmatogenous retinal detachment in the left eye was successfully repaired, with a visual acuity of 20/30. Antecedent upper respiratory infection and headaches and positive serology for the coxsackie virus suggest the possibility of a virus-induced disorder. Genetic studies of this patient showed normal DNA sequences for the bestrophin and peripherin/RDS genes. CONCLUSION: This is the first report of PMS with the following characteristics: occurrence in a woman, development of a rhegmatogenous retinal detachment, and electroretinogram, visual-evoked response, color vision, and OCT findings. PMS has features similar to but also different from those of Harada disease and Best disease. Further studies are necessary to determine its relationship to other acquired conditions, such as virus-induced disorders, and genetic defects unrelated to abnormalities of the bestrophin and peripherin/RDS genes.

Acute Disease↗

The effect of intraoperative retinal manipulation on the underlying retinal pigment epithelium: an experimental study.

PURPOSE: Retinal pigment epithelial changes described after vitreoretinal surgery may result from localized compression injury caused by intentional or inadvertent contact with vitreoretinal instruments. The authors evaluated these changes resulting from manipulation of the retina without frank retinal injury. METHODS: One eye each of six pigmented rabbits underwent surgery during which the inner retinal surface was touched at several points with a 20-gauge silicone-tipped subretinal fluid cannula without causing a retinal break or subretinal hemorrhage. The rabbits were followed-up with indirect ophthalmoscopy, fundus photography, and fluorescein angiography, and were killed at 1 hour, 1 week, or 2 weeks. Light microscopy was used for histopathologic evaluation. RESULTS: On fluorescein angiography, diffuse leakage noted at the injury sites significantly decreased by the fourth day and almost completely disappeared by the second week. Disruption of photoreceptor outer segments and retinal pigment epithelium in the early specimens, and irregular pigmentation, proliferation, and migration of the retinal pigment epithelium at 1 and 2 weeks were the prominent features on histopathologic examination. CONCLUSIONS: Intraoperative manipulation of the attached retina may cause significant pigment epithelium displacement and proliferation and varying degrees of disorganization of normal retinal architecture in the absence of clinically evident retinal breaks and subretinal hemorrhages.

Animals↗

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↗

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

PURPOSE: To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). METHODS: PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. RESULTS: Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. CONCLUSION: PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

Animals↗