Ipsilateral transient amaurosis, mydriasis and light reflex absence after subconjunctival local anesthesia with mepivacaine in three patients with refractory glaucoma - a case report.

BACKGROUND: The subconjunctival anesthesia with local anesthetics is considered as a low-risk procedure allowing ocular surgery without serious complications typical for retro- or parabulbar anesthesia, especially in patients with preexisting Optic Nerve damage. We report development of ipsilateral transient amaurosis accompanied with mydriasis and both, direct and consensual light response absence. CASE PRESENTATION: Three patients with advanced refractory glaucoma undergoing laser cyclophotocoagulation (CPC) for intraocular pressure lowering experienced these adverse effects just few minutes after subconjunctival injection of mepivacaine 2% solution (Scandicaine® 2%, without vasoconstrictor supplementation). The vision was completely recovered to usual values in up to 20 h after mepivacaine application. Extensive ophthalmological examination, including cranial magnetic resonance imaging (MRI), revealed no further ocular abnormalities, especially no vascular constriction or thrombotic signs as well as no retinal detachment. The oculomotor function remained intact. The blockade of ipsilateral ciliary ganglion parasympathetic fibers by mepivacaine may be the responsible mechanism. Systemic pathways as drug-drug interactions seem to be unlikely involved. Importantly, all three patients tolerated the same procedure previously or at a later date without any complication. Overall, our thoroughly elaborated risk management could not determine the causative factor explaining the observed ocular complications just in the current occasion and not at other time points. CONCLUSIONS: Doctors should be aware and patients should be informed about such rare complications after subconjunctival local anesthetics administration. Adequate risk management should insure patients' safety.

Developing an in situ nanosuspension: a novel approach towards the efficient administration of poorly soluble drugs at the anterior eye.

With about 50-60 million cases in the US alone, dry eye disease represents a severe health care problem. Cyclosporin A (CsA) would be a potent candidate for a causal therapy. However, CsA is not sufficiently water soluble to be administrated via simple eye drops. We developed an in situ nanosuspension (INS) as a novel approach towards the administration of CsA to the cornea. It precipitates upon contact with the tear fluid and creates CsA nanoparticles that enter the cornea and release the drug by dissolution. We selected two liquid poly(ethylene glycols) (PEG) that dissolve CsA and create nanoparticles by precipitation of CsA upon water contact. Aqueous solutions of PEG and Solutol, a non-ionic surfactant, were well tolerated by primary human epithelial cells in vitro. To determine the critical water content needed for a precipitation, the solubility of CsA was investigated in quaternary systems of drug, solvent, surfactant and water. The best INS formulation showed a particle size of 505 ± 5 nm, a polydispersity index (PdI) of 0.23 ± 0.03 and a neutral zeta potential of -0.07 ± 0.05 mV. After single administration to porcine eyes in vitro, 3165 ± 597 ng(CsA)/g(cornea) were detected in corneal tissue, while the levels of Restasis a commercial formulation were, with 545 ± 137 ng(CsA)/g(cornea), significantly lower (P<0.01). These results demonstrate that an INS is a promising, novel approach towards the causal treatment of inflammatory diseases at the anterior eye.

Retreatment of full-thickness macular hole: predictive value of optical coherence tomography.

AIM: To determine whether the efficacy of re-operation for idiopathic full-thickness macular hole (FTMH) remaining open after initial surgery with internal limiting membrane (ILM) peeling is correlated with macular hole configuration as determined by optical coherence tomography (OCT), macular hole size, macular hole duration before the first operation, or type of tamponade (gas or silicone oil). METHODS: A retrospective consecutive interventional case series of 28 patients (28 eyes) with a persisting macular hole after vitrectomy, ILM peel, and gas tamponade. 28 patients underwent repeat surgery involving vitrectomy and gas (n = 15) or silicone oil tamponade (n = 12) or no tamponade (n = 1). Autologous platelet concentrate (n = 22), autologous whole blood (n = 1), or no adjuvant (n = 5) was used. Preoperative OCT was undertaken in all eyes. The main outcome measures were anatomical closure and improvement of best-corrected visual acuity (BCVA). RESULTS: Anatomical closure was achieved in 19 of 28 eyes (68%). BCVA improved in 12 eyes, remained unchanged in nine, and worsened in seven. BCVA improved in 11 of 19 eyes with anatomical closure, and in one of eight eyes without closure. Anatomical closure and improvement of BCVA correlated with preoperative macular hole configuration on OCT, with higher rates of closure (18 of 20 eyes versus one of eight eyes, p = 0.001) and greater improvement of BCVA (p = 0.048) in eyes with a cuff of subretinal fluid at the break margin. Macular hole size, type of tamponade, macular hole duration before the first operation, or preoperative BCVA did not significantly correlate with visual or anatomical outcome. CONCLUSION: Macular hole configuration seems to be a strong prognostic indicator of anatomical closure and may help identify those patients most likely to benefit from re-operation.

Ascorbic acid modulates proliferation and extracellular matrix accumulation of hyalocytes.

Ascorbic acid is known to influence proliferation and functional properties of several cell types and is therefore widely used in tissue engineering. In this study, the effect of ascorbic acid on the proliferation and functional properties of hyalocytes was evaluated. Hyalocytes were cultured with different amounts of ascorbic acid in classical two-dimensional (2-D) cultures and a three-dimensional (3-D) pellet culture system. Ascorbic acid enhanced hyalocyte proliferation dose-dependently at concentrations between 0.1 and 3 microg/mL; proliferation was constant over a wide concentration range up to 150 microg/mL, concentrations of 500 microg/mL showed toxic effects. In 2-D hyalocyte culture, the accumulation of glycosaminoglycans (GAG) and collagens increased in response to ascorbic acid supplementation of 10 or 200 microg/mL. Normalized to the cell number, GAG production was not influenced, whereas collagen production increased. These results could be verified in a pellet-like 3-D culture system. Ascorbic acid also influenced hyalocytes on the mRNA level; the expression of COL11A1 was clearly enhanced by ascorbic acid. To conclude, ascorbic acid modulates proliferation and collagen accumulation of hyalocytes; it also influences mRNA expression of the cells. Taken together with the fact that ascorbic acid is present in high concentrations in the vitreous body, this vitamin seems to be an important factor for in vitro hyalocyte culture.

Evaluation of the new photosensitizer Tookad (WST09) for photodynamic vessel occlusion of the choroidal tissue in rabbits.

PURPOSE: To determine the efficacy of Tookad (WST09; Negma-Lerads, Magny-Les-Hameaux, France) photodynamic therapy (T-PDT) by evaluating the angiographic and histologic closure of choroidal vessels at different radiance exposures, drug dosages, and intervals between photosensitizer injection and laser application in a rabbit model. METHODS: Chinchilla Bastard rabbits were injected intravenously with three different dye concentrations (2.5, 5, and 10 mg/kg) before application of light. In every group T-PDT was performed at four different times after injection: 5, 15, 30, and 60 minutes with different radiance exposures ranging from 200 to 3 J/cm2. Fundus photographs and fluorescein angiograms were obtained 90 minutes after injection. Follow-up angiographies were performed at days 1, 3, 7, and 14 after initial treatment. Histology was performed in selected cases immediately after treatment and on days 1, 3, and 7. RESULTS: Immediately after irradiation, most of the visible lesions were angiographically hyperfluorescent due to damaged vessel endothelium and associated RPE damage. Lesions from high-radiance exposures revealed immediate hypofluorescence, indicating vessel closure. Hypofluorescent lesions appeared mainly during day 1 (all lesions angiographically visible, some hypofluorescent) to day 3 (all lesions hypofluorescent) after treatment. At day 7, ophthalmoscopically visible hyperpigmentation took place in all lesions. ED50 thresholds for angiographic hypofluorescence determined at day 3 after treatment with 2.5 mg/kg were 18.8 J/cm2 (5 minutes), 62.0 J/cm2 (15 minutes), and >100 J/cm2 (30 minutes); with 5 mg/kg, 8.4 J/cm2 (5 minutes), 22.8 J/cm2 (15 minutes), 54.5 J/cm2 (30 minutes), and >100 J/cm2 (60 minutes); and with 10 mg/kg, 11.7 J/cm2 (30 minutes) and 54.1 J/cm2 (60 minutes). Histology of the angiographically hypofluorescent lesions revealed vessel thrombosis in all groups 1 hour after PDT up to 7 days after treatment. Sparing of photoreceptors indicated selectivity of T-PDT; however, slight damage was partly observable. After 7 days, localized proliferation of the RPE cells was noted and was enhanced 14 days after treatment. CONCLUSIONS: T-PDT has the potential to achieve selective choroidal vessel occlusion with proper parameter selection, such as (1) 2.5 mg/kg, 5 minutes, 100 J/cm2; (2) 5 mg/kg, 5 minutes, 25 J/cm2; or (3) 5 mg/kg, 15 minutes, 50 J/cm2; however, slight damage to the photoreceptors cannot be ruled out. RPE proliferation indicates primary RPE damage due to PDT, also described with the use of all other photosensitizers.

Noninvasive optoacoustic temperature determination at the fundus of the eye during laser irradiation.

In all fundus laser treatments of the eye, the temperature increase is not exactly known. In order to optimize treatments, an online temperature determination is preferable. We investigated a noninvasive optoacoustic method to monitor the fundus temperature during pulsed laser irradiation. When laser pulses are applied to the fundus, thermoelastic pressure waves are emitted, due to thermal expansion of the heated tissue. Using a constant pulse energy, the amplitude of the pressure wave increases linearly with an increase in the base temperature of between 30 and 80 degrees C. This method was evaluated in vitro on porcine retinal pigment epithelium (RPE) cell samples and clinically during selective RPE treatment with repetitive microsecond laser pulses. During the irradiation of porcine RPE with a neodymium-doped yttrium (Nd:YLF) laser (527 nm, 1.7 micros, 500 Hz repetition rate, 160 mJ/cm(2)) an increase in the base temperature of 30+/-4 degrees C after 100 pulses was found. During patient treatments, a temperature increase of 60+/-11 degrees C after 100 pulses with a 500-Hz repetition rate and 7+/-1 degrees C after 30 pulses with 100 Hz at 520 mJ/cm(2) was found. All measured data were in good agreement with heat diffusion calculations. Optoacoustic methods can be used to noninvasively determine retinal temperatures during pulsed laser treatment of the eye. This technique can also be adapted to continuous-wave photocoagulation, photodynamic therapy and transpupillary thermotherapy, or other fields of laser-heated tissue.