Author: Am J Ophthalmol

Effects of Light Exposure, pH, Osmolarity, and Solvent on the Retinal Pigment Epithelial Toxicity of Vital Dyes

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Purpose: To investigate the in vitro effect of pH, osmolarity, solvent, and light interaction on currently used and novel dyes to minimize dye-related retinal toxicity.Design: Laboratory investigation.Methods: Retinal pigment epithelium (RPE) human cells (ARPE-19) were exposed for 10 minutes to different pH solutions (4, 5, 6, 7, 7.5, 8, and 9) and glucose solutions (2.5%, 5.0%, 10%, 20%, 40%, and 50%) with osmolarity from 142 to 2530 mOsm, with and without 0.5 mg/mL trypan blue. R28 cells were also incubated with glucose (150, 310, and 1000 mOsm) and mannitol used as an osmotic control agent in both experiments. Dye-light interaction was assessed by incubating ARPE-19 for 10 minutes with trypan blue, brilliant blue, bromophenol blue, fast green, light green, or indigo carmine (0.05 mg/mL diluted in balanced saline solution) in the presence of high-brightness xenon and mercury vapor light sources.Results: Solutions with nonphysiologic pH, below 7 and above 7.5, proved to be remarkably toxic to RPE cells with or without trypan blue. Also, all glucose solutions were deleterious to RPE (P < .001) even in iso-osmolar range. No harmful effect was found with mannitol solutions. Among the dyes tested, only light green and fast green were toxic to ARPE-19 (P < .001). Light exposure did not increase RPE toxicity either with xenon light or mercury vapor lamp.Conclusions: Solutions containing glucose as a dye solvent or nonphysiologic pH should be used with care in surgical situations where the RPE is exposed. Light exposure under present assay conditions did not increase the RPE toxicity.

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Ocular Biometry in the Subtypes of Angle Closure: An Anterior Segment Optical Coherence Tomography Study

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Purpose: To evaluate ocular biometric parameters in different subtypes of angle-closure disease in the Iranian population and compare them with normal eyes.Design: Prospective, cross-sectional.Methods: In this clinic-based study, 189 eyes of 154 patients consisting of 40 acute angle-closure glaucoma (AACG) eyes, 40 fellow eyes of AACG, 42 chronic angle-closure glaucoma (CACG) eyes, 40 primary angle-closure suspect (PACS) eyes, and 27 normal eyes underwent complete examination including gonioscopy, A-scan biometry, and anterior segment optical coherence tomography. Only 1 eye of CACG, PACS, and control subjects were selected. Main outcome measures included angle opening distance and trabeculo-iris space area at 500 μm from the scleral spur (AOD500, TISA-500), anterior chamber angle, lens vault, lens thickness, anterior chamber depth (ACD), and lens position.Results: Anterior chamber angle, AOD500, TISA500, ACD, and lens position were less and lens thickness and lens vault were greater in angle-closure than open-angle eyes. ACD was less in AACG than CACG and PACS (P < .001). It was also less in fellow eyes than PACS eyes (P = .04). Lens vault was highest in AACG eyes, followed by fellow eyes, PACS, and CACG. It was significantly more in AACG eyes than CACG and PACS eyes (P < .001 and P = .007, respectively). No difference was observed between AACG and fellow eyes.Conclusions: The anterior segment was crowded in closed-angle compared to open-angle eyes. Higher lens vault may play a role in the development of an acute attack of angle closure.

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Ultrasound Biomicroscopy of the Ciliary Body in Ocular/Oculodermal Melanocytosis

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Purpose: To describe the ultrasound biomicroscopy (UBM) findings of the ciliary body in patients with ocular/oculodermal melanocytosis.Design: Retrospective observational case series study.Methods: A retrospective chart and imaging database review was conducted for patients with unilateral ocular/oculodermal melanocytosis who underwent UBM examination at the Ocular Oncology Clinic of Princess Margaret Hospital. Radial images of the ciliary body at the 3-, 6-, 9-, and 12-o’clock positions were obtained in both eyes. UBM characteristics included ciliary body thickness and reflectivity. The eye with ocular/oculodermal melanocytosis was compared with the contralateral unaffected eye as a control. Statistical significance was analyzed with Student t test.Results: Twelve patients were included. All patients showed unilateral diffuse pigmentation involving episclera and anterior chamber angle. The iris showed diffuse pigmentation in 10 cases and sectorial in 2. Mean ciliary body thickness of the affected eyes was 0.581 ± 0.058 mm (range 0.489-0.744) compared with 0.475 ± 0.048 mm (range 0.406-0.622) in the contralateral eye, which was found to be a statistically significant difference (P < .001). The affected ciliary body showed hyperreflectivity when compared with the unaffected eye. All affected eyes were graded as medium to high reflectivity compared with the unaffected eyes that showed a medium to medium/low reflectivity.Conclusion: Ciliary body involvement in ocular/oculodermal melanocytosis presents as increased thickness and higher ultrasound reflectivity on UBM when compared with the unaffected eye. UBM is helpful in imaging clinically undetectable areas of melanocytosis involving the ciliary body.

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Treatment of Diabetic Macular Edema With a Designed Ankyrin Repeat Protein That Binds Vascular Endothelial Growth Factor: A Phase I/II Study

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Purpose: To evaluate the safety and bioactivity of MP0112, a designed ankyrin repeat protein (DARPin) that specifically binds vascular endothelial growth factor (VEGF) in patients with diabetic macular edema (DME). DARPins are a novel class of proteins selected for specific, high-affinity binding to a target protein.Design: Phase I/II, open-label, multicenter dose-escalation trial.Methods: After a single intravitreal injection of MP0112, the main outcomes were safety assessments, aqueous MP0112 levels, change in best-corrected visual acuity (BCVA), and foveal thickness measured by optical coherence tomography. Six cohorts were planned, but only 3 were enrolled (0.04, 0.15, 0.4 mg), because a maximally tolerated dose of 1.0 mg was identified in a parallel age-related macular degeneration trial.Results: Median aqueous concentration of MP0112 was 555 nM 1 week and >10 nM in 3 of 4 patients 12 weeks post injection of 0.4 mg. Median BCVA improvement at week 12 was 4, 6, and 10 letters in cohorts 1, 2, and 3. Ocular inflammation was observed in 11 patients (61%) and was severe in 1. High-resolution chromatography separated proinflammatory impurities from MP0112, resulting in a new formulation.Conclusions: A single intraocular injection of 0.4 mg MP0112 resulted in levels above the half-maximal inhibitory concentration and neutralization of VEGF in aqueous humor for 8-12 weeks. Despite inflammation in several patients, there was prolonged edema reduction and improvement in vision in several patients. The source of the inflammation was eliminated from a new preparation that is being tested in an ongoing clinical trial.

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