Ocular toxicity of intravitreal clarithromycin.

OBJECTIVE: To investigate the ocular toxicity and clearance of intravitreal clarithromycin lactobionate (Klaricid) and to determine the highest nontoxic dose. MATERIALS AND METHODS: To evaluate toxicity, 24 New Zealand white rabbits were divided into six groups (four rabbits each). Rabbits were examined preoperatively and electroretinography (ERG) was performed. The left eyes of the animals served as controls and received intravitreal injection of 0.1 mL sterile water. Klaricid (0.1 mL) was injected into the midvitreous cavity of the right eyes at concentrations of 25 microg, 250 microg, 500 microg, 1.0 mg, 2.0 mg, and 4.0 mg/0.1 mL. The animals were followed up to 15 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy. Ten New Zealand rabbits were used for the vitreous clearance study as drug test rabbits and two additional rabbits were used to generate control retina and vitreous. The highest nontoxic dose (1 mg) was injected into the vitreous and the concentration of clarithromycin in the vitreous was determined using high-performance liquid chromatography at various time intervals after injection. RESULTS: Cataract occurred after intravitreal doses of 2.0 and 4.0 mg. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 4.0-mg group; it was normal in other groups. Histopathologic sections showed localized retinal necrosis and disorganization with the 2.0 and 4.0 mg dosage. No histologic changes were found in the other groups. The half-life of intravitreal clarithromycin was found to be 2 hours. No metabolites of clarithromycin were observed in the vitreous samples. CONCLUSION: Intravitreal clarithromycin lactobionate is nontoxic to rabbit eyes up to a dose of 1.0 mg. Because of its broad-spectrum antibiotic effect and appropriate half-life in the vitreous, it may be a good choice for intravitreal treatment of susceptible organisms.     

Ocular toxicity of experimental intravitreal itraconazole

We investigated itraconazole, a new triazole antifungal agent that poorly penetrates ocular tissues after oral administration. We injected itraconazole in doses from 10 to 100 micrograms dissolved in 100% dimethyl sulfoxide into the eyes of New Zealand rabbits. Ocular toxicity studies performed five weeks after administration showed no substantial retinal or histopathologic changes in eyes injected with either 100% dimethyl sulfoxide or 10 micrograms of itraconazole. Higher doses caused focal areas of retinal necrosis. Our results indicated that intravitreal doses of 10 micrograms or less of itraconazole may be beneficial in the treatment of fungal endophthalmitis.     

Ocular toxicity after intravitreal injection of terconazole

Terconazole, a new triazole antifungal agent, was injected intravitreally in doses ranging from 10 to 100 micrograms dissolved in dimethyl sulfoxide (DMSO) 60% into the eyes of New Zealand rabbits. Three control eyes received only DMSO. The eyes were evaluated with biomicroscopy, indirect ophthalmoscopy, electroretinography, and histopathologic examination. From these data, it was determined that an intravitreal injection containing a concentration of 10 micrograms/0.1 mL of terconazole is not toxic to the rabbit eye.     

Ocular toxicity of multiple intravitreal DHPG injections

Intravitreal 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG) has been advocated as an alternative mode of therapy in cytomegalovirus (CMV) retinitis in the acquired immunodeficiency syndrome (AIDS) because of toxic neutropenia which is a complication of systemic intravenous DHPG [7]. The recommended regimen requires injection of 200 \gmg DHPG intravitreally twice a week for a period of several weeks to months to control the progression of CMV retinitis [5, 14]. A previous study performed to determine the safe dose of intravitreal DHPG was based on a single intravitreal dose study [101; it does not consider the toxicity which may arise from multiple intravitreal injections of DHPG as it is utilized in the treatment of patients with CMV retinitis. In our study, intravitreal injections of 1000, 400, 200, 100, 50, and 25 \gmg DHPG were administered weekly for a period of 5 weeks in rabbit eyes. Ocular toxicity was monitored using slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy. Electroretinographic evidence of retinal toxicity was found with doses as low as 100 \gmg. Electron-micrographic studies of retinal tissue from the eyes injected with even lower doses (as low as 25 \gmg) also showed evidence of toxic vacuolization in the inner segments of the photoreceptor.     

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.     

Ocular toxicity of intravitreal trovafloxacin in the pigmented rabbit

PURPOSE: Trovafloxacin is an expanded spectrum, newer-generation fluoroquinolone antibiotic with improved Gram-positive and anaerobic activity compared with existing quinolones, while maintaining Gram-negative activity comparable to ciprofloxacin. Given its broad spectrum of activity, trovafloxacin may have potential use for treatment of acute bacterial endophthalmitis. This study examined the toxicity of intravitreally administered trovafloxacin in the pigmented rabbit eye. METHODS: Doses of trovafloxacin ranging from 12.5 microg to 1000 microg were injected into the mid-vitreous of Dutch Belted rabbit eyes. Clinical examination was performed at 1, 3, and 14 days following injection. Animals were sacrificed and eyes were enucleated 14 days following injection. Light microscopy (LM) and transmission electron microscopy (TEM) studies of the optic nerve head, medullary ray, and inferior retina were performed to determine toxicity. RESULTS: At intravitreal doses of 500 microg and less, no toxicity was observed at the ophthalmoscopic or light microscopic level. By TEM, a dose-dependent increase in injury to retinal pigment epithelium, photoreceptors, and nerve fibers in the optic nerve head and medullary ray was observed from 50 microg to 500 microg. No toxicity was noted at doses of 12.5 microg and 25 microg. At doses of 750 microg and above, edema of the medullary ray was noted on ophthalmoscopy. Swelling of the peripapillary medullary ray and necrosis of the inferior retina were evident on LM. CONCLUSION: Intravitreal trovafloxacin doses of 50 microg and higher in the pigmented rabbit eye cause retinal and nerve fiber injury. Intravitreal doses 25 microg and lower appear to be safe, with no evidence of ocular toxicity.     

硅油填充术后眼组织病理改变

目的 探讨硅油对人眼内组织毒副作用的发生时间及机制。 方法 对19例因硅油填充术后严重并发症而摘除的眼球进行组织病理学观察。 结果 在感觉层视网膜、视网膜色素上皮(retinal pigment epithelium,RPE)细胞、视神经、视网膜前膜和下膜、虹膜、前房角、以及角膜内皮中均可见硅油小泡或小滴。在硅油填充短于9个月的眼中,硅油小泡仅见于视网膜表面(视网膜前膜及巨噬细胞内);硅油填充9个月以上的眼中,硅油小泡进入感觉层视网膜内。1例硅油填充39个月的眼中,视神经间质和蛛网膜下间隙受到硅油小泡弥漫性浸润。 结论 眼内硅油填充术后的并发症与硅油在眼内存留的时间长短有关。 (中华眼底病杂志, 1999, 15: 232-234)     

Ocular morbidity associated with intravitreal triamcinolone acetonide

AIM: To report on the complications associated with the use of intravitreal triamcinolone acetonide (IVTA) in a tertiary referral hospital setting. MATERIALS AND METHODS: A retrospective case series review of all IVTA injections carried out over a period of 30 months. RESULTS: One hundred and thirty IVTA injections were performed; nine with limited local follow-up were excluded. Thus, 121 injections (108 patients, 114 eyes) were included in the study. Triamcinolone (4 mg) was used in all cases. Indications were diabetic macular oedema (n=41 eyes), retinal vein occlusions (n=27), postoperative cystoid macular oedema (n=24), exudative age-related macular degeneration (n=16), and others (n=6). No intraoperative complications were recorded. Postoperative intraocular pressure (IOP) readings of 22, 28, 35, and 40 mmHg or higher were recorded in 46.5, 29.8, 12.3, and 7.9% of eyes, respectively. IOP elevation was treated with antiglaucoma medication in all but one eye (0.9%) that required trabeculectomy and one (0.9%) that required vitrectomy with cataract extraction for suspected phacoanaphylactic glaucoma. Two eyes (1.8%) developed retinal detachment; both had previously been treated for retinal breaks. One eye (0.9%) developed culture-positive endophthalmitis. Conclusions: Significant morbidity is associated with IVTA injection; clinicians should be aware when considering treatment options.     

Ocular toxicity of fluoroquinolones

The ocular toxicity of fluoroquinolones and the risks of their use in the treatment of ocular infection were reviewed. Systematic identification, selection, review and synthesis of published English-language studies relating to fluoroquinolone use and safety in animals and humans was conducted. Although not free of complications, fluoroquinolones are generally safe when used to treat ocular infection. Ocular toxicity appears to be dose-dependent and results from class-effects and specific fluoroquinolone structures. Phototoxicity and neurotoxicity have been reported, and toxic effects on ocular collagen may be associated with Achilles tendinopathy. Corneal precipitation may provide an advantageous drug depot but delay healing and result in corneal perforation in approximately 10% of cases. Although human toxicity studies are limited, the current recommended dose for intracameral injection of ciprofloxacin is less than 25 microg. Intravitreal injections of ciprofloxacin 100 microg, ofloxacin 50 microg/mL, trovafloxacin 25 microg or less, moxifloxacin 160 microg/0.1 mL or less and pefloxacin 200 microg/0.1 mL are considered safe.     

Ocular toxicity of tamoxifen

Tamoxifen is a preferred agent for the treatment of breast cancer. While efficacious, it is not without serious side effects. Ocular toxicity to the cornea, retina, and optic nerve have been reported. We present a case of tamoxifen retinopathy and emphasize the need for periodic ophthalmologic examinations to prevent loss of vision.     

Ocular toxicity of hydroxychloroquine

This review summarizes the current literature regarding the ocular complications of hydroxychloroquine. Hydroxychloroquine has been used since the 1950s for the treatment of various rheumatic and dermatologic diseases. Hydroxychloroquine can cause ocular toxicity, with the most serious being an irreversible retinopathy. At the present time, no "gold standard" exists for identification of the ocular toxicity prior to its development. This has led to controversy regarding the recommendations for ophthalmologic examinations for screening patients on hydroxychloroquine.     

Macula toxicity after intravitreal amikacin

Background: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery.
Methods: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis.
Results: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis.
Conclusions: CurrentIy accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.     

Ocular toxicity of styrene

We completed histories and ocular examinations of 345 workers in a styrene plant in order to determine the ocular toxicity of styrene. Despite previous case reports of retrobulbar neuritis and central retinal vein occlusion (associated with a toxic hematopoietic disorder), no such conditions were found in these workers. Conjunctival irritation from styrene was found in 22% of the workers and correlated with intensity of exposure, thus confirming previous reports.     

Comparative toxicity of intravitreal aminoglycoside antibiotics

We compared the toxicity of the aminoglycoside antibiotics (tobramycin, amikacin, netilmicin, and kanamycin) by ophthalmoscopy, light and electron microscopy, and electro-retinography after intravitreal injection in rabbits in doses ranging from 100 to 3,000 micrograms. The earliest manifestations of toxicity were confined to the outer retina with each drug, with lamellar lysosomal inclusions in the retinal pigment epithelium as the earliest finding. However, the aminoglycosides displayed marked differences in the threshold dose required to produce toxic reactions, permitting the following ordering of toxicity: (most toxic) gentamicin greater than netilmicin = tobramycin greater than amikacin = kanamycin (least toxic).     

Presumed macular toxicity of intravitreal antibiotics

BACKGROUND: Intravitreal injection is the most effective route for administration of antibiotics in intraocular infections. PATIENTS AND METHODS: Two patients presented with a metal foreign body in the central vitreous without damage to the retina. RESULTS: Foreign bodies were removed with an intraocular magnet and limited vitrectomy was performed. Because of leukocytic infiltration of the vitreous, 1 mg vancomycin and 0.4 mg amikacin were injected in the vitreous at the end of the surgery. Postoperative visual acuity did not reach preoperative values in both patients. ERG examination revealed reduced photoreceptor activity. We speculate that amikacin may have reached the macula in a high and toxic concentration in an incompletely vitrectomized eye. CONCLUSION: The currently accepted intravitreal use of amikacin may cause retinal toxicity.     

Ocular quinine toxicity.

A case of ocular quinine toxicity is described which showed the typical acute visual loss and subsequent recovery. Vermiform motion of the pupil was noted 48 hours after overdose. This acute effect has not been reported before. Although acute systemic intoxication may respond to removal of quinine from the gut and circulation, there is no evidence that any treatment affects the visual prognosis. The action of quinine on the retina is unknown. We suggest it may block cholinergic neurotransmission in the inner synaptic layer.