INTRAVITREAL DEXAMETHASONE IMPLANT IN RETINITIS PIGMENTOSA-RELATED CYSTOID MACULAR EDEMA.

PURPOSE: To report the clinical outcome after intravitreal dexamethasone implant in patients with retinitis pigmentosa and cystoid macular edema. METHODS: Multicenter retrospective case series of eyes with retinitis pigmentosa and cystoid macular edema that underwent intravitreal dexamethasone implant. Primary outcome measures were best-corrected visual acuity in LogMAR and central macular thickness. Statistical analyses used two-tailed comparison with Wilcoxon signed-rank test. RESULTS: There were a total of 45 eyes from 34 patients with a mean age of 32.7 years (range 16-57) and mean follow-up of 15.5 ± 13.0 months. At Month 3 after the first injection, mean initial best-corrected visual acuity improved from 0.61 ± 0.38 (20/81) to 0.37 ± 0.16 (20/47) (P = 0.012), whereas mean central macular thickness (µm) decreased from 506 ± 288 µm to 311.7 ± 71.6 µm (P < 0.001) and mean intraocular pressure increased from 15.7 ± 2.3 mmHg to 19.8 ± 11.0 mmHg (P = 0.01). Fourteen eyes had multiple injections (1-7 reinjections) at a mean interval of 6 months. Treatment effect was durable with multiple injections, but with seven eyes developing visually significant cataracts. CONCLUSION: Best-corrected visual acuity improved up to 4 months in around half of the eyes. Eyes that benefited the most were pseudophakic, steroid nonresponsive, with large initial central macular thickness, and profuse fluorescein dye leakage.

Novel 'heavy' dyes for retinal membrane staining during macular surgery: multicenter clinical assessment.

PURPOSE: To evaluate the feasibility of two novel 'heavy' dye solutions for staining the internal limiting membrane (ILM) and epiretinal membranes (ERMs), without the need for a prior fluid-air exchange, during macular surgery. METHODS: In this prospective nonrandomized multicenter cohort study, the high molecular weight dyes ILM-Blue™ [0.025% brilliant blue G, 4% polyethylene glycol (PEG)] and MembraneBlue-Dual™ (0.15% trypan blue, 0.025% brilliant blue G, 4% PEG) were randomly used in vitrectomy surgeries for macular disease in 127 eyes of 127 patients. Dye enhanced membrane visualization of the ILM and ERMs, 'ease of membrane peeling', visually detectable perioperative retinal damage, postoperative best-corrected visual acuity (BCVA), dye remnants and other unexpected clinical events were documented by 21 surgeons. RESULTS: All surgeries were uneventful, and a clear bluish staining, facilitating the identification, delineation and removal of the ILM and ERMs, was reported in all but five cases. None of the surgeries required a fluid-air exchange to assist the dye application. BCVA at 1 month after surgery improved in 83% of the eyes in the MembraneBlue-Dual™ group and in 88% in the ILM-Blue™ group. No dye remnants were detected by ophthalmoscopy, and no retinal adverse effects related to the surgery or use of the dyes were observed. CONCLUSION: The 'heavy' dye solutions ILM-Blue™ and MembraneBlue-Dual™ can be injected into a fluid-filled vitreous cavity and may facilitate staining and removal of the ILM and/or ERMs in macular surgery without an additional fluid-air exchange.

Xanthophylls and eye health of infants and adults.

Lutein and zeaxanthin are the only carotenoids present in the eye. They cannot be synthesized de novo and are specifically concentrated in the macula. They appear to have at least two major functions: to filter out blue light and thus prevent ensuing damages to the eye and to act as antioxidants. Infants are particularly at risk from both blue light and oxidative damage to eye tissues. Lutein is present in human milk but is not currently added to infant formulas. Fortifying formulae with lutein in order to match more closely human milk might help protect the infant's sensitive eyes. In adults, the exact pathogenesis of age-related maculopathy remains unknown. Light damage, inflammation, and the disruption of cellular processes by oxidative stress may play an important role in the degenerative process. Manipulation of intake of xanthophylls has been shown to augment macular pigment, therefore it is thought that carotenoid dietary supplements could prevent, delay, or modify the course of age-related maculopathy. However, definite evidence of the effect of carotenoids, the optimal doses to use, and the supplementation duration are still under investigation.

Evaluation of the new photosensitizer Stakel (WST-11) for photodynamic choroidal vessel occlusion in rabbit and rat eyes.

PURPOSE: To evaluate the photodynamic potential of a new hydrosoluble photosensitizer (WST-11, Stakel; Steba Biotech, Toussus-Le-Noble, France), for use in occlusion of normal choroidal vessels in the rabbit eye and CNV (choroidal neovascularization) in the rat eye. METHODS: Occlusive and nonocclusive parameters of Stakel and verteporfin photodynamic therapy (PDT) were investigated in pigmented rabbits. Eyes were followed by fluorescein angiography (FA) and histology at various intervals after PDT. RESULTS: When occlusive parameters (fluence of 50 J/cm(2), 5 mg/kg drug dose and DLI [distance to light illumination] of 1 minute) were used, Stakel PDT was efficient immediately after treatment without associated structural damage of the RPE and retina overlying the treated choroid in the rabbit eye. Two days later, total occlusion of the choriocapillaries was seen in 100% of the treated eyes, along with accompanying histologic structural changes in the overlying retina. When the occlusive parameters (fluence, 100 J/cm2; drug dose, 12 mg/m2; and DLI, 5 minutes) of verteporfin PDT were used, occlusion of the choriocapillaries was observed in 89% of the treated eyes. Histology performed immediately after treatment demonstrated structural damage of the overlying retina and RPE layer. Weaker, nonocclusive Stakel PDT parameters (25 J/cm2, 5 mg/kg, and DLI of 10 minutes) did not induce choriocapillary occlusion or retinal lesions on FA or histology. Weaker, nonocclusive verteporfin PDT parameters (10 J/cm2, 0.2 mg/kg, and DLI of 5 minutes) did not induce choriocapillary occlusion. However, histology of these eyes showed the presence of damage in the retinal and choroidal tissues. Moreover, preliminary results indicate that selective CNV occlusion can be achieved with Stakel PDT in the rat eye. CONCLUSIONS: Unlike verteporfin PDT, Stakel PDT does not cause direct damage to the RPE cell layer or retina. These observations indicate that Stakel PDT may have a high potential for beneficial therapeutic outcomes in treatment of AMD.

Ultrasound biomicroscopy study of the Verisyse aphakic intraocular lens combined with penetrating keratoplasty in pseudophakic bullous keratopathy.

PURPOSE: To evaluate anterior segment modifications after penetrating keratoplasty (PKP), previous anterior chamber intraocular lens (IOL) removal, and Verisyse IOL (AMO) implantation over the iris or under the iris for the treatment of pseudophakic bullous keratopathy (PBK) using ultrasound biomicroscopy. SETTING: Department of Ophthalmology, Poitiers University Hospital, Poitiers, France. METHODS: A prospective randomized comparative case series included 27 patients (27 eyes) with PBK who had PKP and implantation of a Verisyse VRSA54 aphakic IOL. The IOL was implanted over the iris in 13 patients (Group A) and under the iris in a reversed position in 14 patients (Group B). Ultrasound biomicroscopy scans 6 months after surgery measured central anterior chamber depth (ACD), iris thickness (IT), distance of the haptics from the corneal endothelium (CED), distance of the haptics from the ciliary body (CBD), angle opening distance (AOD) 500 mum from the scleral spur (AOD500) and the iridocorneal angle theta on the 4 o'clock meridian lines (AOD3; AOD9; AOD12; AOD6/theta12, theta6, theta3, theta9). RESULTS: No significant difference was found in IT, CBD, or AOD12 between Group A and Group B (P >.05). In Group B, the mean ACD was deeper by approximately 55% (P = .008); CED3 was larger by 69% (P = .0162), CED9 by 80% (P = .0128), AOD3 by 57% (P = .0309), AOD9 by 140% (P = .0057), and AOD6 by 44% (P = .0399); and theta3 was wider by 52% (P = .046), theta9 by 123% (P = .0068), theta12 by 50% (P = .0492), and theta6 by 81% (P = .0237). CONCLUSION: Ultrasound biomicroscopy showed that in eyes that had PKP with Verisyse IOL enclavation to the posterior plane of the iris, which involved posterior translation of the iridal plane, the ACD was significantly deeper and the CED and AOD were significantly larger than in eyes with anterior enclavation of the IOL.

Amniotic membrane transplantation in severe bacterial keratitis.

PURPOSE: To determine whether a combination of early amniotic membrane transplantation (AMT) and early topical corticosteroid treatment could be a safe adjuvant therapy during antibacterial treatment in severe bacterial keratitis (BK) for relieving pain, avoiding iatrogenic epithelial toxicity, and allowing earlier use of topical steroids. METHODS: In a prospective noncomparative case series, 12 patients with severe microscopically-proven BK were treated with immediate maximal topical antibiotics followed by AMT at 48 hours (single-layer epithelial side-down or multilayer epithelial side-up), plus topical steroid treatment at 72 hours. Pain relief (NRS-11 numeric rating pain scale) and the corneal epithelium healing were measured. RESULTS: The follow-up rate was 7.5 person-months, with AMT performed once in 2 patients and twice in 10 patients with BK caused by Pseudomonas aeruginosa (5), Klebsiella pneumoniae (1), Moraxella cattharalis (1), Staphylococcus aureus (1), Staphylococcus epidermidis (2), or Streptococcus pneumoniae (1). A significant decrease in the pain score was noted from the admission day (median, 8; range, 7-10) to shortly after AMT (at day 3: median, 2; range, 1-3). Epithelial healing was achieved between 8 and 45 days (mean, 25.5 +/- 9.7 days). Neither perforation nor neovascularization was observed. CONCLUSIONS: Early AMT combined with topical corticosteroid in severe BK provides immediate pain relief and allows epithelial healing.

Ocular biocompatibility of a poly(ortho ester) characterized by autocatalyzed degradation.

The biocompatibility of autocatalyzed poly(ortho ester) (POE(70)LA(30)), a viscous, hydrophobic, bioerodible polymer, was investigated. POE(70)LA(30) was synthesized, sterilized by gamma irradiation, and injected in rabbit eyes at adequate volumes through subconjunctival, intracameral, intravitreal, and suprachoroidal routes. Clinical examinations were performed postoperatively at regular time points for 6 mo, and histopathologic analysis was carried out to confirm tissular biocompatibility. After subconjunctival injection, the polymer was well tolerated and persisted in the subconjunctival space for about 5 weeks. In the case of intracameral injections, polymer biocompatibility was good; the POE(70)LA(30) bubble was still present in the anterior chamber for up to 6 mo after injection. No major histopathologic anomalies were detected, with the exception of a localized Descemet membrane thickening. After intravitreal administration, POE(70)LA(30) biocompatibility was excellent, and no inflammatory reaction could be detected during the observation period. The polymer was degraded in approximately 3 mo. Suprachoroidal injections of POE(70)LA(30) were reproducible and well tolerated. POE(70)LA(30) triggered a slight elevation of the retina and choroid upon clinical observation. The polymer was detectable in the suprachoroidal space for about 6 mo. No inflammatory reaction and no major retinal anomalies could be detected by histology. In conclusion, POE(70)LA(30) appears to be a promising biomaterial for intraocular application, potentially providing sustained drug delivery over an extended period of time, with a good tolerance.

Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles.

PURPOSE: To study the kinetics of polylactide (PLA) nanoparticle (NP) localization within the intraocular tissues and to evaluate their potential to release encapsulated material. METHODS: A single intravitreous injection (5 micro L) of an NP suspension (2.2 mg/mL) encapsulating either Rh-6G (Rh) or Nile red (Nr) was performed. Animals were killed at various times, and the NPs localization within the intraocular tissues was studied by environmental scanning electron microscopy (ESEM), confocal microscopy, light microscopy histology, fluorescence microscopy, and immunohistochemistry. Eyes injected with blank NPs, free Rh, or PBS solution were used as the control. RESULTS: ESEM showed the flow of the NPs from the site of injection into the vitreous cavity and their rapid settling on the internal limiting membrane. Histology demonstrated the anatomic integrity of the injected eyes and showed no toxic effects. A mild inflammatory cell infiltrate was observed in the ciliary body 6 hours after the injection and in the posterior vitreous and retina at 18 to 24 hours. The intensity of inflammation decreased markedly by 48 hours. Confocal and fluorescence microscopy and immunohistochemistry showed that a transretinal movement of the NPs was gradually taking place with a later localization in the RPE cells. Rh encapsulated within the injected NPs diffused and stained the retina and RPE cells. PLA NPs were still present within the RPE cells 4 months after a single intravitreous injection. CONCLUSIONS: Intravitreous injection of PLA NPs appears to result in transretinal movement, with a preferential localization in the RPE cells. Encapsulated Rh diffuses from the NPs and stains the neuroretina and the RPE cells. The findings support the idea that specific targeting of these tissues is feasible. Furthermore, the presence of the NPs within the RPE cells 4 months after a single injection shows that a steady and continuous delivery of drugs can be achieved.