Jean-Antoine C. Pournaras

Reduction of choroidal neovascularization in mice by adeno-associated virus-delivered anti-vascular endothelial growth factor short hairpin RNA

Strategies leading to the long‐term suppression of inappropriate ocular angiogenesis are required to avoid the need for repetitive monthly injections for treatment of diseases of the eye, such as age‐related macular degeneration (AMD). The present study aimed to develop a strategy for the sustained repression of vascular endothelial growth factor (VEGF), which is identified as the key player in exudative AMD.

Treatment of central retinal vein occlusion-related macular edema with intravitreal bevacizumab (Avastin): preliminary results.

PURPOSE To assess the safety and efficacy of treatment of macular edema secondary to central retinal vein occlusion (CRVO) with intravitreal bevacizumab. PATIENTS AND METHOD The ongoing prospective study included 8 consecutive patients (8 eyes) with macular edema secondary to CRVO (6 non ischemic and 2 ischemic), treated with intravitreal injection of 1.25 mg (0.05 mL) of bevacizumab. Main outcome was best corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by optical coherence tomography monthly during one year. Retreatment criteria include decrease of BCVA, persistence of macular edema on angiograms and increase of CFT. RESULTS Mean age of the eight patients was 68 years (range: 50-82 years). Mean duration of symptoms before injection was 98 days (range: 3-289). Mean follow-up was 3.25 months. At baseline, mean BCVA was 0.84 logMar and mean baseline CFT was 771 microm. Mean BCVA was 0.36 and mean CFT thickness was 275 microm (n = 8) at month 1, 0.41 and 411 microm at month 2 (n = 7), 0.3 and 344 microm at month 3 (n = 6), 0.3 and 397 microm at month 4 (n = 5), respectively. In 75 % of patients, a single injection was not sufficient, and retreatment needed. No serious adverse events were observed. CONCLUSIONS Treatment of macular edema secondary to CRVO with intravitreal bevacizumab injection of 1.25 mg was well tolerated and associated with marked macular thickness reduction and BCVA improvement in all patients. A trend towards reduction of foveal thickness and improvement of visual acuity was observed in both acute and chronic CRVO.

The Vasodilatory Effect of Juxta-arteriolar Microinjection of EndothelinA Receptor Inhibitor in Healthy and Acute Branch Retinal Vein Occlusion Minipig Retinas

Purpose. To investigate the effect of the endothelin(A) receptor inhibitor BQ-123 on the retinal arteriolar vasculature in minipig retinas in normal eyes and eyes with acute branch retinal vein occlusion (BRVO). Methods. Seven healthy eyes of seven minipigs and six eyes of six minipigs with experimental BRVO were evaluated under systemic anesthesia. An intravitreal juxta-arteriolar microinjection of 30 microL BQ-123 0.61 microg/mL (pH 7.4) was performed in all but one eye from each group, into which the physiologic saline vehicle alone was injected. Vessel-diameter changes were measured with a retinal vessel analyzer. Results. In healthy minipig retinas (n = 6), arteriolar diameter (+/-SD) increased 6.19% +/- 3.55% (P < 0.05), 25.98% +/- 2.37% (P < 0.001), 23.65% +/- 1.2% (P < 0.001), and 16.84% +/- 1.95% (P < 0.001), at 1, 5, 10, and 15 minutes, respectively, after BQ-123 microinjection. Two hours after experimental BRVO (n = 5), the retinal arteriolar diameter had decreased (13.07% +/- 5.7%; P < 0.01). One, 5, 10, and 15 minutes after BQ-123 microinjection, retinal arteriolar diameter had increased by 7.14% +/- 3.3% (P < 0.01), 26.74% +/- 7.63% (P < 0.001), 23.67% +/- 6.4% (P < 0.001), and 16.09% +/- 3.41% (P < 0.001), respectively. Vehicle only injection had no vasoactive effect on physiologic or BRVO retinas. Conclusions. A significant increase in retinal arteriolar diameter was demonstrated after juxta-arteriolar BQ-123 microinjection in healthy and in acute BRVO minipig retinas. The results suggest a role for endothelin-1 in maintaining retinal basal arteriolar tone. Reversing the BRVO-related vasoconstriction by juxta-arteriolar BQ-123 microinjection could bring a new perspective to the management of BRVO.

The rationale of retinal endovascular fibrinolysis in the treatment of retinal vein occlusion: from experimental data to clinical application.

Purpose: We describe a retinal endovascular fibrinolysis technique to directly reperfuse experimentally occluded retinal veins using a simple micropipette. Methods: Retinal vein occlusion was photochemically induced in 12 eyes of 12 minipigs: after intravenous injection of 10% fluorescein (1-mL bolus), the targeted retinal vein segment was exposed to thrombin (50 units) and to Argon laser (100–200 mW) through a pars plana approach. A beveled micropipette with a 30-&mgr;m-diameter sharp edge was used for micropuncture of the occluded vein and endovascular microinjection of tissue plasminogen activator (50 &mgr;g/mL) in 11 eyes. In one control eye, balanced salt solution was injected. The lesion site was examined histologically. Results: Retinal vein occlusion was achieved in all cases. Endovascular microinjection of tissue plasminogen activator or balanced salt solution led to reperfusion of the occluded retinal vein in all cases. Indicative of successful reperfusion were the following: continuous endovascular flow, unaffected collateral circulation, no optic disk ischemia, and no venous wall bleeding. However, balanced salt solution injection was accompanied by thrombus formation at the punctured site, whereas no thrombus was observed with tissue plasminogen activator injection. Conclusion: Retinal endovascular fibrinolysis constitutes an efficient method of micropuncture and reperfusion of an experimentally occluded retinal vein. Thrombus formation at the punctured site can be prevented by injection of tissue plasminogen activator.

Ultrasound assessment of ocular vascular effects of repeated intravitreal injections of ranibizumab for wet age-related macular degeneration.

Determine the effect of repeated intravitreal injections of ranibizumab (0.5 mg; 0.05 ml) on retrobulbar blood flow velocities (BFVs) using ultrasound imaging quantification in twenty patients with exudative age‐related macular degeneration treated for 6 months.

Preretinal partial pressure of oxygen gradients before and after experimental pars plana vitrectomy.

Purpose: To evaluate preretinal partial pressure of oxygen (PO2) gradients before and after experimental pars plana vitrectomy. Methods: Arteriolar, venous, and intervascular preretinal PO2 gradients were recorded in 7 minipigs during slow withdrawal of oxygen-sensitive microelectrodes (10-&mgr;m tip diameter) from the vitreoretinal interface to 2 mm into the vitreous cavity. Recordings were repeated after pars plana vitrectomy and balanced salt solution (BSS) intraocular perfusion. Results: Arteriolar, venous, and intervascular preretinal PO2 at the vitreoretinal interface were 62.3 ± 13.8, 22.5 ± 3.3, and 17.0 ± 7.5 mmHg, respectively, before vitrectomy; 97.7 ± 19.9, 40.0 ± 21.9, and 56.3 ± 28.4 mmHg, respectively, immediately after vitrectomy; and 59.0 ± 27.4, 25.2 ± 3.0, and 21.5 ± 4.5 mmHg, respectively, 2½ hours after interruption of BSS perfusion. PO2 2 mm from the vitreoretinal interface was 28.4 ± 3.6 mmHg before vitrectomy; 151.8 ± 4.5 mmHg immediately after vitrectomy; and 34.8 ± 4.1 mmHg 2½ hours after interruption of BSS perfusion. PO2 gradients were still present after vitrectomy, with the same patterns as before vitrectomy. Conclusion: Preretinal PO2 gradients are not eliminated after pars plana vitrectomy. During BSS perfusion, vitreous cavity PO2 is very high. Interruption of BSS perfusion evokes progressive equilibration of vitreous cavity PO2 with concomitant progressive return of preretinal PO2 gradients to their previtrectomy patterns. This indicates that preretinal diffusion of oxygen is not altered after vitrectomy. The beneficial effect of vitrectomy in ischemic retinal diseases or macular edema may be related to other mechanisms, such as increased oxygen convection currents or removal of growth factors and cytokines secreted in the vitreous.

Retinal Embolisation with Localised Retinal Detachment following Retrobulbar Anaesthesia

BACKGROUND The aim of this communication is to describe an unusual and serious complication of retrobulbar anaesthesia for cataract surgery. HISTORY AND SIGNS A 78-year-old female was referred for visual loss (light perception) 24 hours after apparently uneventful cataract surgery with retrobulbar anaesthesia in her left eye. Fundus examination revealed multiple arterial emboli and a localised retinal detachment. MRI revealed a retrobulbar hypersignal of the optic nerve associated with perineuritis. The cardiovascular examination was normal. We assumed this condition resulted from injection of the anaesthetic mixture into the optic nerve. THERAPY AND OUTCOME In order to improve retinal circulation and oxygenation, the intraocular pressure was maximally lowered and anticalcic therapy administered, expecting optimal arterial dilatation. Methylprednisolone (1 g/day 3 days i. v., then rapidly tapered) was also added. The retina slowly reattached but visual acuity remained unchanged. CONCLUSIONS Retrobulbar anaesthesia is routinely used for ocular surgery. Serious complications may still happen, however. This case adds to the previously reported spectrum of complications from retrobulbar anaesthesia.

Conjunctival intraepithelial neoplasia in a patient treated with tacrolimus after liver transplantation.

Purpose: To report a case of conjunctival intraepithelial neoplasia in a patient treated with tacrolimus after liver transplantation for hepatic carcinoma. Methods: Description of the initial clinical presentation of a patient, tumor management, and 15-month follow-up. Results: A 70-year-old man presented with a conjunctival intraepithelial neoplasia that developed on the site of a preexisting pterygium. After total surgical removal and additional application of mitomycin, local tumor control was achieved. Conclusions: We describe a case of intraepithelial conjunctival neoplasia in a patient treated with systemic tacrolimus. Local tumor control was achieved at 15 months after appropriate surgical management.

Successful treatment of longstanding vasospastic central retinal artery occlusion

doi: 10.1111/j.1755-3768.2008.01366.x Editor, C entral retinal artery occlusion (CRAO) of more than 6 hours duration is usually associated with total loss of visual function. In rare cases, visual recovery has been described, probably as a result of spontaneous fragmentation of the embolus and total reperfusion of the retina, but only when this happens within minutes or, at most, a few hours of the occlusion (Duker & Brown 1988). We describe an otherwise healthy patient in whom we documented a 40hour period of almost total loss of vision caused by CRAO, followed by complete visual recovery. A healthy, 67-year-old woman presented with sudden, painless, unilateral visual loss to hand motion only of 40 hours duration. One hour of transient visual loss had preceded this episode. Fundus examination revealed a faint cherry red spot and mild retinal ischaemia (Fig. 1A). Retinal thickness was increased on optical coherence tomography (OCT; Carl Zeiss Meditec Inc., Dublin, CA, USA) (Fig. 1F). Fluorescein angiography (FA) revealed a significant delay in retinal artery filling (Fig. 1D, E). Complete blood count was normal, erythrocyte sedimentation rate was 31 mm in the first hour and c-reactive protein (CRP) was inferior at 5 IU. Echocardiography and carotid Doppler echography showed no significant haemodynamic impairment. Medical work-up did not reveal signs of any vasospastic syndrome.

Effect of systemic nitric oxide synthase inhibition on optic disc oxygen partial pressure in normoxia and in hypercapnia.

PURPOSE To investigate the effect of systemic nitric oxide synthase (NOS) inhibition on optic disc oxygen partial pressure (PO(2)) in normoxia and hypercapnia. METHODS Intervascular optic disc PO(2) was measured in 12 anesthetized minipigs by using oxygen-sensitive microelectrodes placed <50 microm from the optic disc. PO(2) was measured continuously during 10 minutes under normoxia, hyperoxia (100% O(2)), carbogen breathing (95% O(2), 5% CO(2)), and hypercapnia (increased inhaled CO(2)). Measurements were repeated after intravenous injection of N(omega)-nitro-L-arginine methyl ester (L-NAME) 100 mg/kg. Intravenous L-arginine 100 mg/kg was subsequently given to three animals. RESULTS Before L-NAME injection, an increase was observed in optic disc PO(2) during hypercapnia (DeltaPO(2) = 3.2 +/- 1.7 mm Hg; 18%; P = 0.001) and carbogen breathing (DeltaPO(2) = 12.8 +/- 5.1 mm Hg; 69%; P < 0.001). Optic disc PO(2) in normoxia remained stable for 30 minutes after L-NAME injection (4% decrease from baseline; P > 0.1), despite a 21% increase of mean arterial pressure. Optic disc PO(2) increase under hypercapnia was blunted after L-NAME injection (DeltaPO(2) = 0.6 +/- 1.1 mm Hg; 3%; P > 0.1), and this effect was reversible by L-arginine. Moreover, L-NAME reduced the response to carbogen by 29% (DeltaPO(2) = 9.1 +/- 4.4 mm Hg; 49%; P = 0.01 versus before L-NAME). The response to hyperoxia was not affected. CONCLUSIONS Whereas systemic NOS inhibition did not affect optic disc PO(2) in normoxia, a blunting effect was noted on the CO(2)-induced optic disc PO(2) increase. Nitric oxide appears to mediate the hypercapnic optic disc PO(2) increase.