FOVEA PLANA ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: New Perspectives.

PURPOSE: To report on the reliability of optical coherence tomography angiography (OCTA) to diagnose fovea plana. METHODS: A retrospective, cross-sectional, case-control study included patients with foveal persistence of the inner retinal layers, confirmed by spectral domain OCT, and superficial capillary plexus (SCP) and deep capillary plexus foveal vascularization confirmed by OCTA. A healthy control group was selected. The best-corrected visual acuity was obtained. Spectral-domain OCT was used for measuring the outer nuclear layer thickness, and OCTA determined the foveal avascular zone, SCP, and deep capillary plexus vascular density. RESULTS: Optical coherence tomography angiography reliability, based on all parameters, reached 97%, whereas based only on SCP vascular density 91%. The plana group (n = 57) differed significantly from the control group (n = 28) in terms of foveal avascular zone, SCP, and deep capillary plexus foveal vascular density (P < 0.005). Subjects with SCP foveal vascular density >30% or foveal avascular zone <0.1 mm2 had fovea plana. The best-corrected visual acuity of the plana group had no correlation with OCTA quantitative parameters (Pearson |r|<0.18, Spearman |r|<0.44). CONCLUSION: Optical coherence tomography angiography has a high accuracy in diagnosing fovea plana, as its characteristics differ significantly from the normal population. The lack of correlation between the best-corrected visual acuity and OCTA parameters implies that reduced the best-corrected visual acuity is likely to result from coexistent diseases rather than from the foveal structure.

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.

CHANGES IN VISUAL ACUITY AND PHOTORECEPTOR DENSITY USING ADAPTIVE OPTICS AFTER RETINAL DETACHMENT REPAIR.

PURPOSE: To quantify changes in photoreceptor density using adaptive optics fundus camera in patients after retinal detachment (RD) and to correlate them with macular involvement and best-corrected visual acuity. METHODS: At 1 and 3 months (M1 and M3) after vitrectomy, 194 patients underwent adaptive optics imagery in both eyes, at 5 locations, that we matched between time points using anatomical landmarks. Twenty-two patients (10 fovea-OFF [OFF] and 12 fovea-ON [ON]) had matched and analyzable adaptive optics images. We used analysis of variance for repeated measures. RESULTS: Best-corrected visual acuity (logarithm of the minimum angle of resolution and Snellen equivalent [SE]) was significantly different between OFF and ON RDs at baseline: 2.0 (2.3-0.95) (SE: 20/2000) versus 0 (0.1-0) (SE: 20/20); at M1: 0.35 (0.5-0.1) (SE: 20/40) versus 0.05 (0-0.1) (SE: 20/25); and at M3: 0.25 (0.3-0.1) (SE: 20/32) versus 0 (0-0) (SE: 20/20). We observed that cone density was stable in fellow eyes between M1 and M3 (P = 0.67); decreased in treated eyes than in fellow eyes (P < 0.05); and increased postoperatively in the ON group (P = 0.02) but not in the OFF group (P = 0.97). Visual acuity and RD type were independently correlated with cone density (P = 0.004, P = 0.000). CONCLUSION: Postoperative cone density was reduced in OFF RD, but also in the ON group, although the drop recovered during the 3-month follow-up. Cone density was significantly correlated with both visual acuity and type of RD at both time points.

EVOLUTION AND PATTERNS OF CHOROIDAL THICKNESS CHANGES IN RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the changes in choroidal thickness (CT) before and after a successful pars plana vitrectomy for rhegmatogenous retinal detachment (RD), and to compare the evolution of CT with respect to the extent of RD. METHODS: Fifty-four patients were divided into three groups: peripheral macula-on RD (>3 mm from the fovea; 14 eyes); paracentral macula-on RD (fovea-sparing; ≤3 mm from the fovea; 14 eyes); and macula-off RD (involving the fovea; 26 eyes). Choroidal thickness was measured at 1 month (M1) and 3 months (M3) postoperatively, preoperatively in macula-on RDs, with enhanced depth imaging optical coherence tomography, from the nasal side (+2.5 mm) to the temporal side (-2.5 mm) of the fovea. RESULTS: In peripheral macula-on RD, the intereye difference in CTs showed thickening throughout follow-up (subfoveally: preoperatively = 19.6% ± 43.9%, M1 = 22.9% ± 27.5%, M3 = 18.2% ± 35.6%). In paracentral macula-on RD, the intereye difference in CTs showed a thinning throughout follow-up (subfoveally: preoperatively = -7.8% ± 21.9%, M1 =-5.5% ± 26.1%, M3 = -9.3% ± 19.4%), as well as in the macula-off RD (subfoveally: M1 = -14.1% ± 18.7%, M3 = -9.9% ± 15%). CONCLUSION: The extent of RD was related to the evolution of the CT before and after surgery. Further studies are necessary to clarify the relationship between the changes in CT and the effects of circulatory alterations, vitrectomy, and RD.

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.

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.

Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP).

BACKGROUND: Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. METHODS: Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. RESULTS: Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 microm, and decreased significantly to a mean of 224 microm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 microm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. CONCLUSIONS: Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.

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.

Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.

In retinal detachment (RD), photoreceptor death and permanent vision loss are caused by neurosensory retina separating from the retinal pigment epithelium because of subretinal fluid (SRF), and successful surgical reattachment is not predictive of total visual recovery. As retinal iron overload exacerbates cell death in retinal diseases, we assessed iron as a predictive marker and therapeutic target for RD. In the vitreous and SRF from patients with RD, we measured increased iron and transferrin (TF) saturation that is correlated with poor visual recovery. In ex vivo and in vivo RD models, iron induces immediate necrosis and delayed apoptosis. We demonstrate that TF decreases both apoptosis and necroptosis induced by RD, and using RNA sequencing, pathways mediating the neuroprotective effects of TF are identified. Since toxic iron accumulates in RD, we propose TF supplementation as an adjunctive therapy to surgery for improving the visual outcomes of patients with RD.

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.

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.

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).