Photodynamic therapy vs limited macular translocation in the management of subfoveal choroidal neovascularization in pathologic myopia: a two-year study.

PURPOSE: To compare the results of limited macular translocation and photodynamic therapy (PDT) in subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia with a 24-month follow-up. DESIGN: Retrospective analysis of nonrandomized interventional clinical study. METHODS: Retrospective review of 66 consecutive patients: 34 myopic eyes with subfoveal neovascularization treated by PDT and 32 operated on with the translocation technique. Translocation was considered principally when the lesion size was adequate (nasal inferior margin of the membrane less than half a disk diameter away from the center of the fovea) with duration of symptoms of less than four months. Main outcome measure was the postoperative change in visual acuity. RESULTS: In the translocation group, mean gain in visual acuity was greater than in the PDT group (+2.8 lines and -1.8 line, respectively, P = .001). In the translocation group, 55% of eyes gained 3 lines or more at two years compared with 10% in the PDT group. Sixty percent of eyes in the translocation group vs 40% in the PDT group had an improvement of at least five letters. Mean foveal displacement after translocation was 906 mum; postoperative complications included retinal detachment (three eyes), macular fold (one eye), and transient diplopia (four eyes). In young patients, the postoperative gain was better in both groups. In the translocation group, mean survival time for choroidal neovascularization recurrence was 40 months for patients younger than 40 years and 20 months for older patients. CONCLUSIONS: Translocation showed better results than PDT at two years. Further studies are required to confirm these findings.

Iontophoretic delivery of carboplatin in a murine model of retinoblastoma.

PURPOSE: To evaluate the efficacy and dose-response of transcorneoscleral Coulomb controlled iontophoresis (CCI) of carboplatin in the treatment of retinal tumors of a murine model of retinoblastoma. METHODS: Thirty 6-week-old LHBETATAG mice underwent a total of six, serial iontophoretic treatments administered two times per week using a current density of 2.57 mA/cm2 for 5 minutes. Fourteen animals received carboplatin treatments at concentrations of 1.4, 7.0, 10.0, or 14.0 mg/mL without current. Ten control mice underwent treatment with balanced saline solution. RESULTS: A dose-dependent inhibition of intraocular tumor was observed after repetitive iontophoretic treatment. At carboplatin concentrations of 7 mg/mL, 50% of the treated eyes (4/8) exhibited tumor control. No corneal toxicity was observed in eyes treated at carboplatin concentrations under 10 mg/mL. CONCLUSIONS: CCI delivery of carboplatin safely and effectively controls intraocular tumors in a dose-dependent manner in this murine model of retinoblastoma. CCI is a noninvasive, painless option for the focal delivery of carboplatin. However, further clinical and laboratory research is needed before this method of drug delivery is available for children with retinoblastoma.

Ocular aspirin distribution: a comparison of intravenous, topical, and coulomb-controlled iontophoresis administration.

PURPOSE: To evaluate the pharmacokinetics and safety of aspirin delivered by a single, noninvasive, transscleral, coulomb-controlled iontophoresis (CCI) treatment; topical application; or by one intravenous (IV) injection. METHODS: Forty-one adult New Zealand White rabbits received either a single IV injection, topical, or CCI administration of aspirin at a concentration of 10 mg/mL. Histologic evaluation was performed in four CCI-treated eyes to assess safety. Pharmacokinetic distribution in all ocular tissues and fluids was studied at 0.5, 1, 2, 4, 6, and 8 hours after the treatments. Immediately after death, the eyes were dissected and salicylic acid (SA) concentration was determined by HPLC analysis. Blood was sampled at 0.5, 1, 2, 4, 6, and 8 hours, and plasma SA levels for systemic distribution were measured by HPLC analysis. RESULTS: No tissue damage was observed clinically or histologically. SA was found in all tissues and fluids throughout the study period of 8 hours. The highest concentrations of SA were observed with CCI immediately after treatment for all tissues and were the highest SA tissue peaks obtained by the studied delivery methods. IV administration demonstrated a delayed tissue peak of salicylate at 2 hours after administration. At 8 hours, ocular SA concentrations were in the same range for CCI and IV administration. IV injection resulted in blood plasma levels up to 28 times higher than CCI and remained significantly elevated until 8 hours after the treatments. CONCLUSIONS: CCI is a safe and effective method of administering aspirin to the eye while avoiding the systemic side effects associated with IV injection.

Pharmacokinetics of systemic versus focal Carboplatin chemotherapy in the rabbit eye: possible implication in the treatment of retinoblastoma.

PURPOSE: To characterize the pharmacology and toxicity of intravenous versus focal carboplatin delivery in the rabbit eye. METHODS: Pharmacological distribution of carboplatin was examined in New Zealand White Rabbits after a single intravenous infusion of carboplatin (18.7 mg/kg of body weight), a single subconjunctival carboplatin injection (5.0 mg/400 microL), or a single application of carboplatin delivered by Coulomb-controlled iontophoresis (CCI; 14 mg/mL carboplatin, 5.0 mA/cm(2), 20 minutes). After each treatment, animals were euthanatized, and the eyes analyzed at 1, 2, 6, or 24 hours by atomic absorption spectroscopy to determine carboplatin concentration in ocular structures. Potential toxicity of focally delivered carboplatin was assessed by histology after six cycles of 5.0 mg carboplatin delivered by subconjunctival injection or six transscleral carboplatin CCI applications at 72-hour intervals (14.0 mg/mL, 20 minutes at 2.5 mA). RESULTS: Determination of concentrations through atomic absorption spectroscopy in the retina, choroid, vitreous humor, and optic nerve after subconjunctival injection or iontophoretic carboplatin delivery revealed significantly higher levels than those achieved with intravenous administration. Carboplatin concentrations in the blood plasma were found to be significantly higher after intravenous delivery than after focal delivery by subconjunctival injection or CCI. No evidence of ocular toxicity was detected after focally delivered Carboplatin. CONCLUSIONS: Focal administration of carboplatin using subconjunctival or noninvasive CCI safely and effectively transmits this chemotherapeutic drug into the target tissues of the retina, choroid, vitreous, and optic nerve. These results suggest that focal carboplatin delivery may effectively increase intraorbital carboplatin concentrations while decreasing systemic exposure to this cytotoxic drug.

Analysis of retinal flecks in fundus flavimaculatus using high-definition spectral-domain optical coherence tomography.

PURPOSE: To assess morphologic changes associated with retinal flecks in fundus flavimaculatus using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Observational case series. METHODS: Simultaneous recordings of SD-OCT and confocal scanning laser ophthalmoscope (cSLO) fundus autofluorescence images were obtained in fundus flavimaculatus patients. Morphologic aspects of the retinal flecks were analyzed and classified. RESULTS: Thirty-one eyes of 17 consecutive patients (8 male, 9 female; mean age 47.9 +/- 17.1 years) were included for analysis. SD-OCT revealed 5 distinct types of lesions. Group A lesions were limited to the outer segment (OS) of the photoreceptors, the retinal pigment epithelium (RPE) interdigitations, and the RPE/Bruch membrane complex. Group B showed a protrusion of the hyper-reflective material through the interface of inner segment (IS)/OS of the photoreceptors up to the external limiting membrane. A further protrusion of the hyper-reflective material into the outer nuclear layer was seen in group C lesions. Group D lesions were characterized by an accumulation of the hyper-reflective material limited to the outer nuclear layer. Type E lesions can be described as drusen-like retinal pigment detachments. No significant correlation between the different types of flecks and visual acuity was observed (P > .05). CONCLUSIONS: SD-OCT allows one to distinguish at least 5 different types of lesions associated with retinal flecks in fundus flavimaculatus. The ability to characterize the different types of flecks and to analyze the photoreceptor layers surrounding these lesions suggests that SD-OCT might have a potential clinical role in the evaluation and follow-up of the structural changes in fundus flavimaculatus.

Experimental model for proliferative vitreoretinopathy by intravitreal dispase: limited by zonulolysis and cataract.

BACKGROUND: The intravitreal injection of dispase has been shown to be a valuable method for induction of experimental PVR. The goal of the present study was to gain additional information about potential side effects associated with this method. METHODS: Twenty-one pigmented rabbits received a single injection of dispase under topical anesthesia to one eye only, contralateral eyes served as untreated control. The animals were injected with doses from 0.045 to 0.065 units of dispase: 8 animals received 0.045 units, 9 animals 0.055 units and 4 animals 0.065 units. RESULTS: Proliferative vitreoretinopathy occurred in 81% of the treated eyes. In 90% cataract formation was observed. Lens luxation was present in 47.3% of the cataract eyes. CONCLUSION: Intravitreal injection of dispase resulted in the reproducible induction of PVR in addition to cataract formation and lens luxation. Whether these effects may all be associated with a toxic reaction or whether the proliferative changes are solely triggered by endogenous reactions similar to the pathomechanism of human PVR and whether the cataract formation and the lens luxation may be avoided by changing the method of injection require further investigation.

Ocular delivery of acetylsalicylic acid by repetitive coulomb-controlled iontophoresis.

To investigate the potential of transscleral coulomb-controlled iontophoresis (CCI) for repetitive delivery of acetylsalicylic acid (ASA) into the eye, a total of 50 rabbits was included in this study. Fourteen animals received serial CCI treatment. Fourteen animals underwent CCI with either ASA or balanced salt solution (BSS) for at least 6 days at 24- and 48-hour intervals. Eighteen animals received a single CCI application, while 18 animals were injected with 15 mg ASA/kg body weight intravenously. HPLC analysis was performed to determine the levels of salicylic acid (SA) in ocular tissues. Apart from clinical follow-up, 2 rabbits in the ASA and BSS groups were examined by electroretinography, and 2 animals were examined histologically. Though high concentrations of SA were measured, no alterations were observed clinically, histologically and electrophysiologically. Repetitive CCI demonstrated its potential as a topical drug delivery system for ASA into the eye. This transscleral delivery of ASA resulted in significant and sustained intraocular concentrations of SA without side effects. Iontophoresis may be advantageous in clinical administration maintaining therapeutic levels of ASA while avoiding adverse effects associated with the systemic administration of nonsteroidal anti-inflammatory drugs.