Prediction of Postoperative Visual Outcome in Patients with Idiopathic Epiretinal Membrane.

PURPOSE: The aim of this study was to estimate the association between preoperative characteristics in subjects with idiopathic epiretinal membrane (ERM) and visual acuity improvement after vitrectomy and create an algorithm for predicting postoperative visual outcome. METHODS: In a retrospective, cross-sectional study, we included adults with idiopathic ERM and excluded subjects with low-quality scans, other ocular conditions, and previous surgery except cataract surgery. Baseline characteristics were extracted from medical files, spectral-domain OCT, and OCT angiography. Visual improvement was expressed as a binary variable. RESULTS: Fifty-four subjects were included in the study. Three months postoperatively, 30 subjects improved, 10 remained stable, and 14 deteriorated. Spearman correlation showed no correlation between variables and visual acuity improvement (<0.39). Reduced dimensionality showed that baseline visual acuity, lens status, foveal aspect, spherical equivalent, and 2 interactive variables including foveal aspect and lens status have the strongest effect on improvement. Five-fold logistic regression based on these variables provided a model with AUC 0.9 ± 0.06. CONCLUSION: No variable has a direct predictive role on visual acuity improvement; however, baseline visual acuity, lens status, foveal aspect and spherical equivalent, when combined, provide a predictive model that could serve as a tool for more informed decisions.

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

PURPOSE: 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. METHODS: Visual acuity (ETDRS), central macular thickness (OCT), peak-systolic, end-diastolic and mean-BFVs in central retinal (CRA), temporal posterior ciliary (TPCA) and ophthalmic (OA) arteries were measured before, 2 days, 3 weeks and 6 months after the first injection. Patients were examined monthly and received 1-5 additional injections depending on ophthalmologic examination results. RESULTS: Six months after the first injection, a significant increase in visual acuity 50.9 ± 25.9 versus 44.4 ± 21.7 (p < 0.01) and decrease in mean central macular thickness 267 ± 74 versus 377 ± 115 µm (p < 0.001) were observed compared to baseline. Although mean-BFVs decreased by 16%±3% in CRA and 20%±5% in TPCA (p < 0.001) 2 days after the first injection, no significant change was seen thereafter. Mean-BFVs in OA decreased by 19%±5% at week 3 (p < 0.001). However, the smallest number of injections (two injections) was associated with the longest time interval between the last injection and month 6 (20 weeks) and with the best return to baseline levels for mean-BFVs in CRA, suggesting that ranibizumab had reversible effects on native retinal vascular supply after its discontinuation. Moreover, a significant correlation between the number of injections and percentage of changes in mean-BFVs in CRA was observed at month 6 (R = 0.74, p < 0.001) unlike TPCA or OA. CONCLUSION: Ranibizumab could impair the native choroidal and retinal vascular networks, but its effect seems reversible after its discontinuation.

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-µm 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.

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

BACKGROUND: 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. METHODS: We have employed short hairpin (sh)RNAs combined with adeno-associated virus (AAV) delivery to obtain the targeted expression of potent gene-regulatory molecules. Anti-VEGF shRNAs were analyzed in human retinal pigment epithelial (RPE) cells using Renilla luciferase screening. For in vivo delivery of the most potent shRNA, self-complementary AAV vectors were packaged in serotype 8 capsids (scAAV2/8-hU6-sh9). In vivo efficacy was evaluated either by injection of scAAV2/8-hU6-sh9 into murine hind limb muscles or in a laser-induced murine model of choroidal neovascularization (CNV) following scAAV2/8-hU6-sh9 subretinal delivery. RESULTS: Plasmids encoding anti-VEGF shRNAs showed efficient knockdown of human VEGF in RPEs. Intramuscular administration led to localized expression and 91% knockdown of endogenous murine (m)VEGF. Subsequently, the ability of AAV2/8-encoded shRNAs to impair vessel formation was evaluated in the murine model of CNV. In this model, the sizes of the CNV were significantly reduced (up to 48%) following scAAV2/8-hU6-sh9 subretinal delivery. CONCLUSIONS: Using anti-VEGF vectors, we have demonstrated efficient silencing of endogenous mVEGF and showed that subretinal administration of scAAV2/8-hU6-sh9 has the ability to impair vessel formation in an AMD animal model. Thus, AAV-encoded shRNA can be used for the inhibition of neovascularization, leading to the development of sustained anti-VEGF therapy.

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-µm-diameter sharp edge was used for micropuncture of the occluded vein and endovascular microinjection of tissue plasminogen activator (50 µg/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.

Effects of rat anti-VEGF antibody in a rat model of corneal graft rejection by topical and subconjunctival routes.

PURPOSE: To compare the effect of a rat anti-VEGF antibody, administered either by topical or subconjunctival (SC) routes, on a rat model of corneal transplant rejection. METHODS: Twenty-four rats underwent corneal transplantation and were randomized into four treatment groups (n=6 in each group). G1 and G2 received six SC injections (0.02 ml 10 µg/ml) of denatured (G1) or active (G2) anti-VEGF from Day 0 to Day 21 every third day. G3 and G4 were instilled three times a day with denatured (G3) or active (G4) anti-VEGF drops (10 µg/ml) from Day 0 to Day 21. Corneal mean clinical scores (MCSs) of edema (E), transparency (T), and neovessels (nv) were recorded at Days 3, 9, 15, and 21. Quantification of neovessels was performed after lectin staining of vessels on flat mounted corneas. RESULTS: Twenty-one days after surgery, MCSs differed significantly between G1 and G2, but not between G3 and G4, and the rejection rate was significantly reduced in rats receiving active antibodies regardless of the route of administration (G2=50%, G4=66.65% versus G1 and G3=100%; p<0.05). The mean surfaces of neovessels were significantly reduced in groups treated with active anti-VEGF (G2, G4). However, anti-VEGF therapy did not completely suppress corneal neovessels. CONCLUSIONS: Specific rat anti-VEGF antibodies significantly reduced neovascularization and subsequent corneal graft rejection. The SC administration of the anti-VEGF antibody was more effective than topical instillation.

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.

Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin(®) ) in neovascular age-related macular degeneration.

PURPOSE: Angiogenic inhibitors, alone or combined with other therapies, are believed to represent a promising treatment for neovascularization in age-related macular degeneration (wet AMD). They can maintain or improve visual acuity (VA), at least for the first 2years. However, evolution to retinal atrophy cannot be ruled out and it may be useful to assess the effects of antiangiogenic therapy on retinal and choroidal circulation. METHODS: We carried out a pilot study in 15 patients with wet AMD. Time-averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before and 4weeks after a single intravitreal injection of 1.25mg bevacizumab in 0.05ml. Patients underwent two ophthalmic examinations, before and 4weeks after injection, including VA measurement and optical coherence tomography (OCT3) examination. RESULTS: In treated eyes, bevacizumab injection was followed by a significant improvement in VA (from 20/125 to 20/80; p=0.0214), and a decrease in mean central macular thickness (from 392±96µm to 271±50µm; p=0.0038). Mean BFV decreased by 10% in the CRA (p=0.0226), 20% in the TPCA (p=0.0026) and 20% in the OA (p=0.0003). No effect was observed in fellow eyes. CONCLUSIONS: Intravitreal bevacizumab acutely improved VA and reduced central macular thickness in wet AMD. Ultrasound imaging revealed that BFVs decreased in all retrobulbar arteries, suggesting that after local diffusion, bevacizumab exerts a short-term regional effect. Bevacizumab might therefore induce hypoperfusion of the whole eye, which may correspond to a vascular side-effect.

Vitrectomy may prevent the occurrence of diabetic macular oedema.

PURPOSE: This study aimed to demonstrate that vitrectomy may prevent the occurrence of diabetic macular oedema (DMO). METHODS: Three patients with diabetes type 1 underwent vitrectomy in one eye to treat complications of proliferative diabetic retinopathy. RESULTS: During follow-up, all patients suffered unilateral macular oedema in the non-vitrectomized eye as a result of general metabolic changes. In two of these patients, the DMO resolved with management of the underlying medical condition. CONCLUSIONS: These case reports suggest the vitreous may play a role in the occurrence of DMO associated with general risk factors. Further studies are needed to increase understanding of the mechanisms involved in the development and progression of DMO.

Spectral domain optical coherence tomography in diabetic macular edema.

BACKGROUND AND OBJECTIVE: To compare the images obtained from Stratus time domain optical coherence tomography (OCT) (Carl Zeiss Meditec, Inc., Dublin, CA) and Cirrus spectral domain OCT (Cirrus HD-OCT 4000 model; Carl Zeiss Meditec, Inc.) in patients with diabetic macular edema. PATIENTS AND METHODS: This observational retrospective case series was created using the charts of 20 patients with diabetes mellitus diagnosed as having diabetic macular edema. All patients had both Stratus and Cirrus OCT imaging completed on the same day. Qualitative comparisons were performed by two experienced clinicians in an unmasked fashion. Central macular thickness and central foveal thickness were recorded. RESULTS: Thirty-six eyes of 20 patients with diabetes mellitus were analyzed. Features such as cystoid spaces, highly reflective lesions, vitreoretinal interface, serous retinal detachment, and photoreceptors inner/outer segments were more often detected with the Cirrus OCT than with the Stratus OCT. Considering the same reference lines for evaluation of central macular thickness and central foveal thickness, the same values were obtained with both devices. CONCLUSION: Cirrus OCT enables easier observation of normal structures and retinal abnormalities than the Status OCT. Furthermore, lesions may be accurately identified and quantified by the Cirrus OCT.

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.

Intravitreal ranibizumab (Lucentis) for the treatment of myopic choroidal neovascularization.

BACKGROUND: Macular choroidal neovascularization (CNV) is one of the most vision-threatening complications of myopia, which can lead to severe vision loss. The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab in the treatment of myopic CNV. METHODS: We conducted a prospective, consecutive, interventional study of patients with subfoveal or juxtafoveal CNV secondary to pathologic myopia (PM) treated with intravitreal injection of ranibizumab in the Jules Gonin University Eye Hospital from June 2006 to February 2008. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and fluorescein angiography (FA) were performed at baseline and monthly for all patients. Indications for retreatment were loss in BCVA associated either with persistent leakage from CNV shown on FA, and/or evidence of CNV activity on OCT. RESULTS: The study included 14 eyes of 14 patients. The mean spherical equivalent refractive error was -12.5 (range, -8.0 D to -16.0 D). Mean time of follow-up was 8.4 months (range from 3 to 16 months, SD: 3). The mean number of intravitreal injections administered for each patient was 2.36 (SD 1.5). The mean initial visual acuity (VA) was 0.19 decimal equivalent (log-MAR: 0.71, SD: 0.3). A statistically significant improvement to a mean VA of 0.48 decimal equivalent (log-MAR:0.32, SD: 0.25) was demonstrated at the final follow-up. VA improved by a mean of 3.86 (SD 2.74) lines. Nine patients (64%) demonstrated a gain of 3 or more lines. Mean central macular thickness (CMT) measured with OCT was 304 microm (SD: 39) at the baseline, and was reduced significantly at the final follow-up to 153 microm (SD: 23). Average CMT reduction was 170 microm (SD: 57). No injection complications or drug-related side effects were noted during the follow-up period. CONCLUSIONS: In this small series of eyes with limited follow-up, intravitreal ranibizumab was a safe and effective treatment for CNV secondary to PM, resulting in functional and anatomic improvements.

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.

Diagnosis and management of enophthalmos.

Enophthalmos is a relatively frequent and misdiagnosed clinical sign in orbital diseases. The knowledge of the different etiologies of enophthalmos and its adequate management are important, because in some cases, it could be the first sign revealing a life-threatening disease. This article provides a comprehensive review of the pathophysiology, evaluation, and management of enophthalmos. The main etiologies, such as trauma, chronic maxillary atelectasis (silent sinus syndrome), breast cancer metastasis, and orbital varix, will be discussed. Its objective is to enable the reader to recognize, assess, and treat the spectrum of disorders causing enophthalmos.

Optical coherence tomography and multifocal electroretinogram findings in chronic solar retinopathy.

PURPOSE: To correlate the structural and functional retinal defects, which are induced photochemically in chronic solar retinopathy. DESIGN: Observational case report. METHODS: Four emmetropic eyes of two patients, previously diagnosed with chronic solar retinopathy, were evaluated by optical coherence tomography (OCT), multifocal electroretinography, and fluorescein angiography. RESULTS: Visual acuity ranged from 20/80 to 20/50 and all subjects had central and steady fixation. In all eyes, OCT demonstrated a hyporeflective space at the level of outer retinal and retinal pigment epithelium (RPE) layers, which was limited to the fovea. The foveal contour was preserved with normal vitreoretinal interface. Multifocal electroretinogram (mfERG) trace array of the first-order kernel demonstrated attenuated responses extending to a larger area, the para- and perifovea. A foveal RPE window defect was angiographically evident in all cases. CONCLUSIONS: A model of centrifugal neuronal damage is proposed for chronic solar retinopathy, with more functional than structural neuroretinal defects.

Effect of carbogen breathing and acetazolamide on optic disc PO2.

PURPOSE: Acetazolamide was previously shown to increase optic disc partial pressure of oxygen (PO(2)). The study was conducted to evaluate optic disc PO(2) variations during normoxia, hyperoxia (100% O(2)), and carbogen breathing (95% O(2), 5% CO(2)), before and after intravenous administration of acetazolamide. METHODS: PO(2) measurements were obtained at intervascular areas of the optic disc in nine anesthetized minipigs using oxygen-sensitive microelectrodes (10-microm tip diameter) placed at <50 microm from the optic disc. PO(2) was measured continuously during 10 minutes under normoxia, hyperoxia, or carbogen breathing. Oxygen measurements were repeated under these conditions after intravenous injection of acetazolamide (500-mg bolus). RESULTS: In hyperoxia, optic disc PO(2) increased moderately (DeltaPO(2) = 4.81 +/- 1.16 mm Hg (mean +/- SD; 24%; P < 0.001) after a much larger increase in systemic PaO(2). Carbogen breathing induced a significant increase in both systemic PaO(2) and PaCO(2), which resulted in a large increase in optic disc PO(2) (DeltaPO(2) = 13.17 +/- 2.18 mm Hg; 67%; P < 0.001). Acetazolamide induced a slow and progressive increase in both systemic PaCO(2) and optic disc PO(2) (30 minutes DeltaPO(2) = 4.24 +/- 2.45 mm Hg; 24%; P < 0.04). However, it was when carbogen was simultaneously administered that optic disc PO(2) increased most substantially (DeltaPO(2) = 18.91 +/- 5.23 mm Hg; 90%; P < 0.002). CONCLUSIONS: Carbogen breathing increases optic disc Po(2) significantly in minipigs, more than hyperoxia. The association of acetazolamide injection with carbogen breathing could induce an additional increase in optic disc PO(2) through the effect of higher systemic PaCO(2).

Experimental retinal vein occlusion: effect of acetazolamide and carbogen (95% O2/5% CO2) on preretinal PO2.

PURPOSE: To evaluate the variations of preretinal oxygen partial pressure (Po(2)) in normal and in ischemic postexperimental branch retinal vein occlusion (BRVO) areas, during normoxia, hyperoxia (100% O(2)), and carbogen (95% O(2), 5% CO(2)) breathing before and after intravenous injection of acetazolamide. METHODS: Preretinal Po(2) measurements were obtained in intervascular retinal areas, distant from the retinal vessels of 13 anesthetized mini-pigs with oxygen-sensitive microelectrodes (10 microm tip diameter) introduced through the vitreous cavity by a micromanipulator. The microelectrode tip was placed <50 microm from the vitreoretinal interface in the preretinal vitreous. Po(2) was measured continuously for 10 minutes under systemic normoxia, hyperoxia, and carbogen breathing. A BRVO was induced with an argon green laser, and oxygen measurements were repeated under normoxia, hyperoxia, and carbogen breathing, before and after intravenous injection of acetazolamide (500 mg bolus). RESULTS: In hyperoxia, a moderate nonsignificant preretinal Po(2) increase in both normal (DeltaPo(2) = 2.20 +/- 4.16 mm Hg; n = 25) and ischemic retinas (DeltaPo(2) = 4.30 +/- 3.57 mm Hg; n = 16) was measured in spite of a substantial increase in systemic Pao(2). Carbogen breathing induced a significant increase in systemic Paco(2) and a higher systemic Pao(2) than hyperoxia. Furthermore, it significantly increased the preretinal Po(2) in normal areas (DeltaPo(2) = 19.37 +/- 16.41 mm Hg; n = 26), and in ischemic areas (DeltaPo(2) = 14.94 +/- 8.53 mm Hg; n = 14). Intravenous acetazolamide did not affect the preretinal Po(2). Acetazolamide induced an increase of the preretinal Po(2) to a greater extent when it was associated with carbogen breathing (DeltaPo(2) = 15.15 +/- 9.15 mm Hg; n = 7) than when it was combined with hyperoxia (DeltaPo(2) = 6.96 +/- 4.49 mm Hg; n = 7). CONCLUSIONS: Carbogen breathing significantly increased preretinal Po(2) in normal and in ischemic postexperimental BRVO areas of mini-pigs. The concomitant use of acetazolamide injection and carbogen breathing or hyperoxia could restore an appropriate oxygenation of BRVO areas.