Abdul Ahad Kazi

Retinal Toxicity of Triamcinolone Acetonide in Silicone-Filled Eyes

OBJECTIVE To determine the retinal toxicity of triamcinolone acetonide at different doses in vitrectomized, silicone-filled rabbit eyes. MATERIALS AND METHODS Vitrectomy with silicone oil placement was performed in 32 rabbit eyes. A dosage of 1 mg/0.025 mL, 2 mg/0.05 mL, or 4 mg/0.1 mL of triamcinolone acetonide was injected intravitreally in the study group eyes; the control group received 0.1 mL of sterile saline. Electroretinography and retinal histology were performed to evaluate toxicity. RESULTS No retinal toxicity was seen in the groups given 1, 2, and 4 mg of triamcinolone acetonide or in the control group. ERG and histologic sections in all groups were normal. No drug was visible in the vitreous cavity at the end of the 140-day period (average) in eyes injected with 4 mg of triamcinolone acetonide. CONCLUSIONS Up to 4 mg of triamcinolone acetonide can be safely injected in silicone-filled, vitrectomized eyes without any significant retinal toxicity.

Evaluation of toxicity of intravitreal ceftazidime, vancomycin, and ganciclovir in a silicone oil-filled eye.

PURPOSE To evaluate the toxicity of intravitreal drugs in an eye filled with silicone oil for prolonged internal retinal tamponade. METHODS Vitrectomy was performed in 21 rabbit eyes, and the vitreous was replaced with silicone oil. Different concentrations of various drugs (ceftazidime, vancomycin, and ganciclovir) were injected intravitreally. RESULTS Silicone oil increased the toxicity of these drugs, which were injected in previously determined nontoxic doses, possibly because of a reduction of the preretinal space. Injecting one quarter of the known nontoxic dose failed to show any toxicity. CONCLUSIONS Nontoxic concentrations of intravitreal drugs can cause toxicity in a silicone-filled eye.

Problems with and pitfalls of photodynamic therapy.

OBJECTIVE To delineate the various factors that may influence the outcome of photodynamic therapy of the retina and choroid. DESIGN Experimental animal study. ANIMALS Pigmented and nonpigmented rabbits; rhesus monkeys. INTERVENTION The hydrophilic photosensitizer, mono-L-aspartyl chlorin e6, which is maximally activated at 664 nm, was studied after intravenous injection into pigmented and nonpigmented rabbits and rhesus monkeys. Laser light was supplied by a red diode laser coupled to a modified slit-lamp biomicroscope and delivered to the ocular fundus after passing through a standard fundus contact lens. Standard photodynamic parameters were used. The effects of fundus pigmentation, intraocular pressure, spot focus and defocus, region of fundus treated, equivalent fluence, and retreatment were observed in the different animal species. MAIN OUTCOME MEASURES Slit-lamp biomicroscopy, fluorescein angiography, light and transmission electron microscopy. RESULTS Fundus pigmentation appeared to be a factor only at the lowest fluence level tested, where only 4 of 12 lesions attempted in pigmented fundi were noted on fluorescein angiography, compared with 12 of 12 lesions in albino rabbits. At normal intraocular pressures and a given fluence, 10 of 10 lesions were fully manifested on fluorescein angiography, compared with 4 of 10 at 30 mmHg and 0 of 10 at pressures sufficient to blanch the optic nerve (>60 mmHg). For laser spots either focused or defocused, there were 6 of 6 lesions that were fully manifested on fluorescein angiography for each of the parameters. Lesions treated in the fovea resulted in larger spots on fluorescein angiography. The fluence of 5 mW for 10 seconds resulted in a larger lesion on angiography than the equivalent fluence of 10 mW for 5 seconds. Areas of retreatment in rabbits demonstrated more thinning of the neurosensory retina and loss of photoreceptor outer segments and nuclei than corresponding areas receiving one treatment. CONCLUSIONS Photodynamic therapy results varied, depending on intraocular pressure, region of fundus treated, ocular pigmentation, and the total time of exposure to the photosensitizer. Retreatment resulted in progressive thinning of the neurosensory retina with loss of photoreceptor outer segments and nuclei in the rabbit eye.

Intravitreal Toxicity Of Moxifloxacin

Purpose: To assess the retinal toxicity of various concentrations of intravitreally administered moxifloxacin, a fourth-generation fluoroquinolone. Methods: Ten New Zealand albino rabbits were divided into five groups. The initial concentration of moxifloxacin (400 mg/250 mL) was titrated using 5% dextrose solution to concentrations (320 &mgr;g/0.1 mL, 160 &mgr;g/0.1 mL, 100 &mgr;g/0.1 mL, and 50 &mgr;g/0.1 mL) that were injected intravitreally into 1 eye of each rabbit. Two control eyes were injected intravitreally with 0.1 mL of 5% dextrose solution. All animals were examined before and after injection by indirect ophthalmoscopy and slit-lamp biomicroscopy; electroretinography (ERG) was performed on all animals. The animals were killed, and their eyes were enucleated and examined with light microscopy. Results: Remarkable decreases in ERG findings were noted in the group injected with moxifloxacin at a concentration of 320 &mgr;g/0.1 mL. No meaningful ERG changes were observed in eyes injected with moxifloxacin at other concentrations. There were no signs of retinal toxicity during slit-lamp examination, indirect ophthalmoscopy, or light microscopy in any eyes injected with moxifloxacin concentrations of ≤160 &mgr;g/0.1 mL. Conclusions: Intravitreal injection of moxifloxacin at a concentration of ≤160 &mgr;g/0.1 mL appeared nontoxic in the rabbit eye.

Inhibition of experimental angiogenesis of cornea by various doses of doxycycline and combination of triamcinolone acetonide with low-molecular-weight heparin and doxycycline.

Purpose: To evaluate the effect of topically administered doxycycline in various doses; the combination of triamcinolone acetonide and low-molecular-weight heparin (LMWH); and the combination of triamcinolone acetonide and doxycycline on experimental corneal neovascularization in rats. Methods: This project is the combination of 2 separate studies. First, the chemical cauterization of corneas in 36 eyes of 36 Long Evans male rats was performed by using silver nitrate/potassium nitrate sticks. Topical instillation of doxycycline at 0.05% (pH = 3.3), 0.1% (pH = 3.1), 1% (pH = 2.3), 2% (pH = 2.1), 2% (pH neutralized to 7.4), and normal saline continued for 7 days. Second, the chemical cauterization of the corneas in 24 eyes of 24 rats was achieved by application of silver nitrate/potassium nitrate sticks. Topical instillation of triamcinolone acetonide (10 μg/mL) and either LMWH (10 mg/mL) or doxycycline (10 mg/mL) was compared with normal saline treatment of 7 days. For both studies, the percent area of the cornea covered by neovascularization and scar in each group was calculated separately by using computer software on digital photographs. All corneas were evaluated histopathologically in study and control groups. Results: The mean percent area of corneal neovascularization determined in the eyes given doxycycline 0.05%, 0.1%, 1%, 2%, and 2% (pH neutralized) study groups and control groups was 69.8% ± 18.0%, 64.5% ± 14.0%, 56.4% ± 20.8%, 54.8% ± 6.0%, 36.2% ± 4.3%, and 69.4% ± 5.7%, respectively. The mean of percent area of neovascularization in the 2% doxycycline (pH neutralized) doxycycline group was significantly less than that of the control group and the <1% doxycycline concentrations (P < 0.05). The percent corneal neovascularization in the 2% (pH neutralized) doxycycline group was not significantly different from that of the 1% and 2% doxycycline groups (P < 0.05). There was no significant difference in percent area of corneal scar between control and study groups (P > 0.05). The mean percent area of corneal neovascularization in triamcinolone acetonide and LMWH, triamcinolone acetonide and doxycycline, and control groups was 2.35% ± 4.42%, 9.42% ± 6.8%, and 64.7% ± 10.0%, respectively. The mean percent area of neovascularization in the triamcinolone acetonide plus LMWH or triamcinolone acetonide plus doxycycline groups was significantly different from that of the control group (P = 0.001 for both). There was no significant difference between study groups with regard to percent area of neovascularization or percent area of corneal scar between the control and study groups. Conclusions: Topically administered combinations of triamcinolone acetonide plus LMWH or triamcinolone acetonide plus doxycycline had effects that contributed to efficient suppression of corneal neovascularization; these drugs were ineffective at similar concentrations used alone. Topically administered 2% (pH neutralized) doxycycline has antiangiogenic effects, which contributed to significant suppression on corneal neovascularization. This drug may be therapeutically beneficial in treatment of corneal neovascularization in clinical trials.

Intravitreal Toxicity of Levofloxacin and Gatifloxacin

To determine whether prone postoperative near visual acuity following macular hole surgery can be used as a reliable indicator of successful hole closure, data from 21 patients undergoing macular hole surgery were collected. Seventeen of the 18 patients with hole closure and all 3 patients with persistent macular holes had a Rosenbaum acuity better than preoperative visual acuity, yielding 94% sensitivity, 0% specificity, 85% positive predictive value, and 0% negative predictive value. Fourteen of the 18 patients with macular hole closure and all 3 patients with persistent macular holes had a Rosenbaum acuity better than 20/40, yielding 78% sensitivity, 0% specificity, 82% positive predictive value, and 0% negative predictive value. Although postoperative near visual acuity can predict macular hole closure with 94% sensitivity, the test is not clinically useful to predict hole closure because of the high surgical success rate of macular hole surgery. The test could be useful in encouraging patients to maintain head prone positioning and alleviate patient anxiety.

Threshold power levels for NPe6 photodynamic therapy

OBJECTIVE To determine the threshold power levels for producing retinal and choroidal vascular occlusion using mono-L-aspartyl chlorin e6 (NPe6) photodynamic therapy; to evaluate its efficacy with longer intervals between photosensitizer injection and laser application; to determine the elapsed time between light application and appearance of angiographic changes. METHODS Pigmented and nonpigmented rabbits were injected intravenously with 2 mg/kg of NPe6 before laser irradiation of the retina-choroid. Group 1 was treated at increasing power levels; fluorescein angiograms were obtained at each fluence. Group 2 animals were exposed to laser irradiation at 5 minutes, and 1 and 3 hours postinjection to determine (by fluorescein angiography 24 hours post-treatment) if increasing the interval affected outcome. Group 3 animals underwent fluorescein angiography at 30 minutes, 1 hour, 2 hours, and 24 hours posttreatment to document the time between laser application and subsequent vessel closure. RESULTS Choroidal vessel occlusion was angiographically evident in all lesions at fluences of > or = 2.65 J/cm2 in pigmented rabbits and at > or = 0.88 J/cm2 in nonpigmented rabbits. Lesion diameter decreased as the time between injection and treatment increased. Vessel occlusion was documented at least 2 hours after treatment. CONCLUSION Choroidal vessel occlusion can occur at very low fluence.

Threshold and Retreatment Parameters of NPe6 Photodynamic Therapy in Retinal and Choroidal Vessels

BACKGROUND AND OBJECTIVE To determine the threshold fluence for producing choroidal and retinal vascular occlusion with mono-L-aspartyl chlorin e6 (NPe6) photodynamic therapy (PDT) during primary treatment and the effect of retreatment. METHODS Primary treatment: Rats, rabbits, and monkeys underwent NPe6 PDT to determine the threshold fluences for choroidal and retinal vessel occlusion. The threshold was determined by analyzing fluorescein angiograms for areas of nonperfusion. Retreatment: Dutch-belted rabbits underwent NPe6 PDT followed by fluorescein angiography. Rabbits were retreated one week later at the same parameters. RESULTS Fluence levels and vascular damage thresholds were always higher for retinal than for choroidal vascular occlusion. Retreatment caused choroidal vessel closure at all tested fluences but retinal capillaries closed only at a fluence > 17.7 J/cm2. CONCLUSION NPe6 PDT has a lower threshold to occlude choroidal vessels than retinal vessels. The cumulative effect of retreatment does not damage retinal vessels unless the threshold is exceeded during a single retreatment session.

Intravitreal toxicity of garenoxacin.

Purpose: To assess the retinal toxicity of varying concentrations of intravitreally injected garenoxacin. Methods: Twenty eyes of 20 New Zealand albino rabbits were used for this study. The animals were anesthetized with ketamine (35–50 mg/kg) and xylazine (3–5 mg/kg). Garenoxacin was titrated using distilled water to the following concentrations: 4,000, 2,000, 1,000, 400, 200, and 100 &mgr;g/0.1 mL. Each concentration was injected intravitreally (0.1 mL) into three rabbit eyes. Three control eyes were injected with 0.1 mL of balanced saline solution. All animals were examined before and after injection by indirect ophthalmoscopy and slit-lamp biomicroscopy. Electroretinography was performed on all animals before intravitreal injection and 14 days after injection. The animals were examined by indirect ophthalmoscopy and slit-lamp biomicroscopy before they were killed; the eyes were enucleated and examined with light microscopy. Results: No electroretinographic changes or signs of retinal toxicity by slit-lamp examination, indirect ophthalmoscopy, or light microscopy were seen in any eyes 14 days after intravitreal injection of garenoxacin (≤4,000 &mgr;g/0.1 mL). Conclusions: Garenoxacin injected intravitreally appeared safe at concentrations of ≤4,000 &mgr;g/0.1 mL.

Fluorescence Properties of a Hydrophilic Sensitizer in Pigmented Rats, Rabbits, and Monkeys

BACKGROUND AND OBJECTIVE To evaluate fluorescence properties of mono-L-aspartyl chlorin e6 (NPe6; Meija Seika Kaisha, Ltd., Tokyo, Japan) photodynamic therapy, which allows real-time simultaneous imaging of choroidal and retinal vasculature during treatment without the addition of another dye. MATERIALS AND METHODS Four pigmented rabbits, 4 pigmented rats, and 2 African green monkeys were administered intravenous injections of the NPe6 dye. The animals were immediately placed in front of the scanning laser ophthalmoscope and the fundus was viewed with the helium-neon laser. The resulting fluorescence was viewed and recorded on super-VHS videotape. RESULTS Fluorescence demonstrated clearly that NPe6 entered the retinal and choroidal circulation within seconds of intravenous injection. The concentration of NPe6 was diminished over a period of 1.5 hours in the monkey and 5 hours in the rat, as evidenced by considerable diminution of the intensity of fluorescence. CONCLUSION NPe6 fluorescence allows evaluation of drug availability within the retinal and choroidal circulation and visualization of pathological lesions before commencement of photodynamic therapy.