Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.

PURPOSE: To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. DESIGN: Randomized, open-label, multicenter superiority study. PARTICIPANTS: Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium. METHODS: Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 µg], and 20% sulfur hexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal tPA [50 µg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. MAIN OUTCOME MEASURES: The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. RESULTS: Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference ß, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group. CONCLUSIONS: Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Real-World Outcomes of Ranibizumab Treatment in French Patients with Visual Impairment due to Macular Edema Secondary to Retinal Vein Occlusion: 24-Month Results from the BOREAL-RVO Study.

INTRODUCTION: Information about real-world ranibizumab use is needed to optimize treatment of macular edema secondary to retinal vein occlusion (RVO). The BOREAL-RVO study assessed treatment use, effectiveness, and safety of 24-month treatment with ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to RVO in a real-world setting. METHODS: This was a multicenter, post-authorization, observational study in France, including patients starting ranibizumab for RVO. Primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 6. Secondary endpoints were mean changes from baseline in BCVA at month 24 and central retinal thickness (CRT) at months 6 and 24, and treatment use in real-world setting. RESULTS: 226 branch RVO (BRVO) and 196 central RVO (CRVO) patients were enrolled; 71.7% and 70.9% completed the 24-month follow-up, respectively. In BRVO, mean (SD) baseline BCVA was 55.2 (18.7) letters, with gains of 14.3 (13.7), 14.1 (16.5), 13.0 (17.5), and 11.4 (20.1) letters at months 3, 6, 12, and 24, respectively. In CRVO, mean (SD) baseline BCVA was 40.4 (25.6) letters, with gains of 16.0 (21.2), 9.5 (25.4), 9.2 (27.7), and 8.3 (23.8) letters at months 3, 6, 12, and 24, respectively. At month 24, 52% of BRVO and 41% of CRVO patients had gains of 15 or more letters. In BRVO, mean (SD) CRT values at baseline and months 3, 6, 12, and 24 were 550 (175), 315 (104), 343 (122), 335 (137), and 340 (105) µm. In CRVO, mean (SD) CRT values at baseline and months 3, 6, 12, and 24 were 643 (217), 327 (152), 400 (203), 379 (175), and 348 (161) µm. On average, BRVO patients had 3.8 injections for 6.9 visits by month 6, and 7.2 injections for 19.7 visits by month 24. CRVO patients had 2.7 injections for 4.2 visits by month 6 and 7.1 injections for 21.1 visits by month 24. Factors predictive of better BCVA gain at month 6 were age under 60 at baseline, lower baseline BCVA and BCVA gain at month 3. There were no new safety findings. CONCLUSION: Major improvements in BCVA and CRT were observed at month 3 after the induction phase and then were sustained up to month 24, with a slight decrease, probably due to under-treatment. This study demonstrated ranibizumab to be a safe and effective treatment for BRVO and CRVO in the real-world setting, although more regular or proactive treatment could further improve outcomes.

Lens-Iris diaphragm retropulsion syndrome: Risk factors and management. A prospective study.

PURPOSE: The lens-iris diaphragm retropulsion syndrome (LIDRS) corresponds to an acute deepening of the anterior chamber during phacoemulsification. LIDRS is painful for the patient and sometimes causes intraoperative complications. This study was designed to assess the preoperative risk factors of LIDRS and its outcome. SETTING: Monocentric study in the university department of ophthalmology, Intercommunal Hospital Center, Creteil, France. DESIGN: Prospective observational study. METHODS: Preoperative parameters of consecutive patients who underwent cataract surgery were recorded. LIDRS occurrence was evaluated during surgery and classified into 3 stages. Except for the first patient, a simple and rapid maneuver to separate the iris from the capsule was performed in all patients with LIDRS. RESULTS: LIDRS occurred in 101 out of 205 included eyes: mild in 73.2%, marked in 16.8%, and severe in 9.9%. LIDRS patients were younger, and had a longer axial length and a thinner lens than the control group (p < 0.01 for all). Univariate logistic regression showed that the main predictive factors of LIDRS were long axial length and decreased lens thickness. LIDRS occurred in 83% (5/6) of eyes with prior vitrectomy. Complications occurred (zonular dehiscence, lens or IOL dislocation), especially in vitrectomized eyes. The maneuver separating the iris from the capsule allowed almost all eyes to restore normal chamber depth and prevent complications. CONCLUSIONS: Myopia and prior vitrectomy were the main risk factors of LIDRS. The maneuver separating the iris from the capsule allowed almost all eyes to resolve LIDRS. Analysis of preoperative factors can help the surgeon identify patients at risk and prevent patient pain and intraoperative complications associated with LIDRS.

Long-term follow-up of retinal sensitivity assessed by microperimetry in patients with internal limiting membrane peeling.

PURPOSE: To evaluate anatomical and functional changes in patients with vitreomacular interface disease after internal limiting membrane (ILM) peeling, using microperimetry along with usual clinical and multimodal retinal imaging. METHODS: Patients with vitreomacular interface disease requiring vitrectomy underwent multimodal retinal evaluation, including visual acuity assessment, fundus color photograph, Spectral-Domain Optical Coherence Tomography, Optical Coherence Tomography-Angiography, and microperimetry. They were examined at baseline (M0), 6 months (M6) and 18 months (M18) after surgery. Retinal sensitivity was subdivided into three concentric polygons: Large, Medium, Small. RESULTS: Eleven eyes of 11 patients were analyzed, including 10 epiretinal membranes (ERMs). Best-corrected visual acuity (BCVA) improved in all patients from 0.51 logarithm of the minimal angle of resolution (logMAR) to 0.067 (p = 0.0074). Retinal sensitivity improved between M0 and M6 in all polygons and continued to improve between M6 and M18 for polygons Medium (M) and Small (S) with no statistical significance. At M18, BCVA and retinal sensitivity were similar in the operated eye compared with the fellow eye for all patients. Dissociated optic nerve fiber layer appearance was observed in 8 patients at M18. It was not correlated with either retinal sensitivity or BCVA or microscotomas. No recurrence of ERM or macular hole occurred during follow-up. CONCLUSION: After surgery, the retinal sensitivity assessed by microperimetry gradually improved until the 18th month and was not different from the values of the fellow eye. These results seemed to confirm that ILM peeling can be an effective and safe technique to treat patients with vitreomacular interface disease.

Prognostic factors of idiopathic epiretinal membrane surgery and evolution of alterations of the central cone bouquet.

PURPOSE: To describe the structural changes observed postoperatively in epiretinal membranes (ERM), in particular the alterations in the central cone bouquet (CB), and to identify prognostic factors that might predict postoperative outcome. METHODS: We included 125 eyes of 117 patients who underwent idiopathic ERM removal with at least a 6-month follow-up. For each patient, spectral-domain optical coherence tomography (SD-OCT) was performed and best-corrected visual acuity (BCVA) was measured, before and after surgery. RESULTS: Before surgery, 44 eyes (35.2%) presented CB alterations: 65.9% a cotton ball sign, 15.9% a foveolar detachment and 18.2% a pseudovitelliform lesion. Median BCVA increased from 20/63 to 20/32 post-operatively (p = .001) with a mean follow-up of 17 months. The disappearance of CB alterations after surgery was observed in 97.7% of eyes. In stage 3 and 4 ERM, ectopic inner foveal layers persisted in 76.7% of eyes after surgery. Postoperative BCVA was correlated with change in central macular thickness and initial BCVA and was not correlated with the presence of preoperative CB alteration, the initial stage of ERM, the presence of postoperative dissociated optical nerve fiber layer, and the disappearance of ectopic inner fiber layers. The combination of cataract surgery and capsulotomy did not seem to change visual outcome and seemed to accelerate visual recovery. Incidentally, general anesthesia was correlated with final BCVA. CONCLUSION: ERM surgery allowed a significant gain in BCVA and the disappearance of CB alterations in the great majority of cases. CB alteration did not show to be associated with poor visual prognosis.

Real-World Outcomes after 36-Month Treatment with Ranibizumab 0.5 mg in Patients with Visual Impairment due to Diabetic Macular Edema (BOREAL-DME).

PURPOSE: To assess the efficacy, safety, and follow-up of 36-month treatment with ranibizumab in patients with diabetic macular edema (DME) in real-life setting. METHODS: This is a prospective phase 4 observational study. Between December 2013 and April 2015, 84 ophthalmologists enrolled a total of 290 adult patients initiating ranibizumab for visual impairment due to DME and treated them according to their routine practice. The primary outcome (mean change in best-corrected visual acuity [BCVA] after 12 months) was previously reported. Here, we present outcomes after 36 months of follow-up for BCVA and change in central subfield thickness (CSFT) and report how participating ophthalmologists treated DME over a 3-year period (number of visits and injections and evolution of treatment strategy). RESULTS: Of the 290 patients enrolled, 187 (64.5%) completed the 36 months of the study (entire cohort). In the entire cohort, 97 patients were treated exclusively with ranibizumab throughout the study, and 90 patients switched to other intravitreal treatments. Mean BCVA was 64.2 (20.1) letters, representing a gain of +4.1 (19.9) letters from baseline to month 36 (M36). CSFT improved over the study, and by M36 had decreased by 127 (138) µm compared to baseline. Over the 36 months of follow-up, patients in the entire cohort paid their ophthalmologists a mean of 30.9 (12.2) visits and had a mean of 7.6 (5.2) any injections. Results for quality of life questionnaires NEI-VFQ25 and HUI-3 remained stable throughout the study. Multivariate analysis on the 145 patients with evaluable BCVA data at M36 found that male gender and milder baseline DME characteristics (BCVA ≥59 and CSFT <500 µm) were predictive factors for achieving a BCVA of ≥70 letters at M36. This study did not find any new safety signals, compared to the known profile of ranibizumab. CONCLUSIONS: Gains in BCVA in this real-life study were lower than those observed in randomized clinical trials with ranibizumab, mainly due to undertreatment. Safety analysis of ranibizumab did not yield any new safety concerns.

Real-World Outcomes with Ranibizumab 0.5 mg in Patients with Visual Impairment due to Diabetic Macular Edema: 12-Month Results from the 36-Month BOREAL-DME Study.

PURPOSE: To report the real-world effectiveness and safety of ranibizumab 0.5 mg in patients with visual impairment due to diabetic macular edema (DME). METHODS: This is a French, 36-month, multicenter, observational cohort study. Between December 2013 and April 2015, ophthalmologists enrolled diabetic patients aged ≥18 years with DME-related visual impairment and for whom ranibizumab 0.5 mg was initiated. Here, we present the 12-month results from this cohort. The primary endpoint was the mean change in best-corrected visual acuity (BCVA); sample size calculations were based on RESTORE trial data (BCVA mean change = 6.8 letters, preci sion = 0.7 letters). Secondary endpoints included the change in central subfield thickness (CSFT), number of visits, number of injections received, and frequency of ocular and nonocular adverse events and serious adverse events. RESULTS: Between December 2013 and April 2015, a total of 290 patients with DME were enrolled by 84 ophthalmologists; 12-month data are available for 242 patients (due to low recruitment rates, precision was recalculated for 242 evaluable patients: the precision was then of 1.0 letters). Mean age (± standard deviation) was 66.1 ± 11.0 years and 56.6% were male. The mean baseline BCVA and CSFT were 59.2 letters (95% confidence interval [CI] 57.3, 61.0) and 457 µm (95% CI: 438, 476), respectively. At month 12, the mean gain in BCVA from baseline was 7.4 letters (95% CI: 5.4, 9.4), with 36.8% of patients with BCVA > 70 letters versus 13.2% at baseline. Mean change in CSFT was -125 µm (95% CI: -146, -103). The mean number of ranibizumab injections was 5.1 ± 2.3 over an average of 10.4 ± 3.0 visits. No new safety findings were identified. CONCLUSIONS: The BOREAL study confirms the effectiveness and safety of ranibizumab for the treatment of DME-related visual impairment in routine clinical practice with fewer injections than reported in clinical trials.

Retinal Vein Occlusions.

Retinal vein occlusions (RVOs) have been defined as retinal vascular disorders characterized by dilatation of retinal veins with retinal and subretinal hemorrhages, macular edema, and a varying degree of retinal ischemia. Retinal angiography, either as fluorescein and indocyanine green (ICG) angiography or in the form of optical coherence tomography (OCT)-based angiography, is essential for the diagnosis and assessment of the prognosis of RVOs. It allows the differentiation of diverse types of RVOs, such as perfused or nonperfused, as well as the detection of different modalities in the natural history of RVOs. OCT angiographic imaging in combination with dye angiography (fluorescein or ICG) is the most effective method to assess the amount and location of cystoid macular edema and the persistence, regression, and degree of ischemia. OCT can additionally display the presence and integrity of the outer limiting membrane and of the inner and outer segments of the photoreceptors as useful biomarkers for the prognosis and as a guide for the treatment of RVO. Due to the relatively often benign and self-limiting course of nonischemic RVOs, therapy may initially be delayed. If macular edema extends into the foveolar region and persists, intravitreal medical therapy including steroids (triamcinolone; fluocinolone or dexamethasone in slow-release devices) and/or anti-VEGF (vascular endothelial growth factor) drugs (bevacizumab, ranibizumab, aflibercept) may be intravitreally administered, avoiding the irreversibly destructive effect of laser coagulation, which previously was applied in a 'grid' pattern over the extrafoveolar leaking area. The side effects of intraocularly applied steroids in relatively young patients including cataract formation and ocular hypertension have to be considered.

QUALITATIVE AND QUANTITATIVE FOLLOW-UP USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL VEIN OCCLUSION TREATED WITH ANTI-VEGF: Optical Coherence Tomography Angiography Follow-up of Retinal Vein Occlusion.

PURPOSE: To evaluate changes of vascular flow of patients treated with intravitreal injections of anti-vascular endothelial growth factor for macular edema secondary to retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA). METHODS: Patients with RVO with macular edema and treated with intravitreal injections of anti-vascular endothelial growth factors were retrospectively evaluated. The following examinations were performed before and after treatment: best-corrected visual acuity, spectral domain optical coherence tomography, fluorescein angiography, and OCTA (Optovue, Inc). Automatic measurement of vascular density of the superficial and deep capillary plexus was also performed and compared with age- and sex-matched healthy subjects. RESULTS: Twenty-eight eyes of 28 patients (mean age 66.2 years; males 19%) were evaluated, including 13 central RVO, 11 branch RVO, and 4 hemicentral RVO. After treatment, mean central macular thickness significantly decreased from 644 µm to 326 µm and best-corrected visual acuity increased from 20/125 to 20/63 (P < 0.01 for both results). On OCTA, perifoveal capillary disruption (P = 0.029) and the number of cysts in the superficial capillary plexus and deep capillary plexus (P < 0.002) significantly decreased after treatment. The mean vascular density in the superficial capillary plexus slightly decreased during follow-up from 46.44% to 45.01% (not significantly). These densities were significantly less than those observed in healthy controls (P < 0.001). CONCLUSION: Optical coherence tomography angiography showed regression of macular edema, reduced capillary disruption and cysts, and slight decrease in mean macular vascular density with time and despite treatment. Thus, OCTA enables qualitative and quantitative evaluation during follow-up of patients treated for RVO.

Optical coherence tomography angiography in retinal vein occlusion treated with dexamethasone implant: a new test for follow-up evaluation.

PURPOSE: To quantitatively and qualitatively analyze patients with macular edema secondary to retinal vein occlusion (RVO) and treated with the intravitreal dexamethasone implant using optical coherence tomography angiography (OCTA). METHODS: The files of patients treated with intravitreal injection of dexamethasone implant for macular edema secondary to RVO were retrospectively analyzed. Before and after injection, the following data were recorded: best-corrected visual acuity (BCVA), central macular thickness (CMT) measured using spectral-domain optical coherence tomography, fluorescein angiography, and OCTA (Optovue, Inc., Fremont, CA, USA). Results of automatic measurement of vascular density of the superficial capillary plexus (SCP) and deep capillary plexus were obtained before and after treatment and compared to those of healthy subjects matched for age and sex. RESULTS: Seven eyes of 7 patients (mean age, 76 years; 57% male) were analyzed, including 3 cases of central RVO and 4 cases of branch RVO. All patients received 1 intravitreal injection of dexamethasone implant. After a mean follow-up of 2 months, CMT significantly decreased from 657 µm to 324 µm on average and BCVA increased from 20/100 to 20/50 (p = 0.017 and p<0.001, respectively). At the SCP, the mean whole en face vascular density slightly decreased during follow-up from 43.21% to 42.76% (not statistically significant). Vascular densities were largely inferior to those observed in control subjects (p≤0.01 in all quadrants). CONCLUSIONS: This study confirms the potential contribution of OCTA as a novel noninvasive imaging technology that enables a quantitative and qualitative evaluation of the follow-up of macular edema in RVO. Optical coherence tomography angiography may complement advantageously multimodal imaging to monitor patients with RVO.

Optical Coherence Tomography Angiography in Retinal Vein Occlusion: Evaluation of Superficial and Deep Capillary Plexa.

PURPOSE: To evaluate the optical coherence tomography angiography (OCT angiography) appearance of the superficial and deep capillary plexa in eyes with retinal vein occlusion (RVO) and to compare these findings with those of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD OCT). DESIGN: Retrospective observational case series. METHODS: Patients presenting with RVO to Creteil University Eye Clinic were retrospectively evaluated. All patients had undergone a comprehensive ophthalmic examination including FA, SD OCT, and OCT angiography. RESULTS: There were 54 (31 male, 57%) RVO patients with a mean age of 70 years. The perifoveal capillary arcade was visible in 52 of 54 eyes (96%) on OCT angiography and in 45 eyes (83%) on FA; this arcade was disrupted in 48 eyes (92%) and 39 eyes (72%) on OCT angiography and FA, respectively (P = .002). Perifoveal capillary arcade disruption was correlated with peripheral retinal ischemia (P = .025). Intraretinal cystoid spaces were observed in 34 eyes (68%) using FA, in 40 eyes (76%) using SD OCT, and in 49 eyes (90%) using OCT angiography (P = .008 for OCT angiography vs SD OCT and P = .001 for OCT angiography vs FA). Retinal capillary network abnormalities were observed in all patients in both superficial capillary plexus and deep capillary plexus on OCT angiography. Nonperfusion grayish areas were more frequent in the deep capillary plexus (43 eyes, 84%) than in the superficial capillary plexus (30 eyes, 59%, P < .001). CONCLUSION: OCT angiography can simultaneously evaluate both macular perfusion and edema. For the first time, an imaging technique enables the evaluation of the deep capillary plexus, which appears to be more severely affected than the superficial capillary plexus in RVO.

Comparison of macular choroidal thickness in adult onset foveomacular vitelliform dystrophy and age-related macular degeneration.

PURPOSE: To compare macular choroidal thickness (MCT) in eyes with adult onset foveomacular vitelliform dystrophy (AOFVD) and eyes with AMD. METHODS: Five groups of 38 eyes each were included in a prospective, observational, comparative study: AOFVD eyes with fluid accumulation; AOFVD fellow eyes without fluid (early stage); advanced exudative (wet) AMD; advanced dry AMD; and healthy normal eyes. All study eyes underwent a comprehensive ophthalmologic examination. Macular choroidal thickness was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). RESULTS: Subfoveal choroidal thickness (SFCT) in AOFVD with subretinal fluid (325.66 ± 85.98 µm) was significantly (P < 0.001) thicker compared with that in exudative AMD (158.55 ± 57.87 µm) and in dry AMD (157.53 ± 67.08 µm). Also, in AOFVD, the choroid was significantly (P = 0.001) thicker than that in the normal group (255.87 ± 87.46 µm). However, in AOFVD, there was no significant difference (P = 0.69) between the SFCT in the study eye and in the fellow eye (317.66 ± 90.04 µm). The choroidal thickness at each of the other 12 measured points showed similar results. CONCLUSIONS: This study demonstrates choroidal thickening in AOFVD in contrast with the choroidal thinning observed in advanced AMD. These findings suggest that the pathogenic mechanisms in AOFVD are different from those in exudative AMD. Choroidal thickness measurement could help differentiate the challenging diagnosis between exudative AMD and the advanced stage of AOFVD (with fluid accumulation but without choroidal neovascularization).

Macular edema in central retinal vein occlusion: correlation between optical coherence tomography, angiography and visual acuity.

To analyze the characteristics and the course of macular edema secondary to central retinal vein occlusion (CRVO) using optical coherence tomography (OCT) and to determine correlations between clinical, tomographic and angiographic data, in particular including retinal ischemia. In this retrospective study, 53 consecutive patients with CRVO were included. At each follow-up visit, patients underwent complete ophthalmological examination, including best-corrected visual acuity (BCVA) and OCT. Fluorescein angiography was performed at baseline and on demand during follow-up. 243 OCTs were analyzed. Mean age was 61 years and mean follow-up 13 months. The first structural change, observed very early after the onset of the occlusion, was a diffuse increase at the level of the outer nuclear layer without change at the level of the inner retina. This early change seemed characteristic of retinal vein occlusion. Cystoid spaces were subsequently observed in all retinal layers and were combined with serous retinal detachment in 51 %. During the first 6 months, central retinal thickness was higher in ischemic CRVO (mean, 691 µm) than in non-ischemic CRVO (mean, 440 µm, p < 0.01). In eyes with foveal thickness (central retinal thickness without subretinal fluid) of 700 µm or greater, peripheral ischemia was present in 69 % of eyes, final BCVA was 20/200 or less in 75 % and never reached 20/40 during follow-up. The integrity of the junction of the photoreceptors' inner and outer segments was correlated with a better prognosis (p < 0.05). Foveal thickness was inversely correlated to BCVA at each visit and could have a prognostic value. OCT examination in CRVO revealed useful data for the diagnosis of CRVO and its prognosis. The largest macular edemas seemed to be the hallmark of ischemic CRVO.

SD-OCT pattern of retinal venous occlusion with cystoid macular edema treated with Ozurdex®.

PURPOSE: To report our experience with sustained-release dexamethasone 0.7 mg intravitreal implant (Ozurdex®; Allergan, Inc., Irvine, CA) in retinal vein occlusion with macular edema. METHODS: A prospective study of a series of 9 patients with recent retinal vein occlusion with macular edema treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed. Complete ophthalmic examination including visual acuity, fundus biomicroscopy, fundus photography, fluorescein angiography, and spectral domain optical coherence tomography (Spectralis SD-OCT; Heidelberg Engineering, Heidelberg, Germany) was performed at baseline and follow-up (1 week, 1 month, and 3 months), and tolerability of the implant was assessed. RESULTS: Nine eyes of 9 consecutive patients treated with a total of 9 sustained-release dexamethasone 0.7 mg intravitreal implants for macular edema associated with retinal vein occlusion were included. Five patients had central retinal vein occlusion and 4 patients had branch retinal vein occlusion. Accentuated ischemia was associated in 2/5 patients with central retinal vein occlusion. All eyes showed SD-OCT evidence of decreased edema following implant placement (mean decrease in central retinal thickness 320 µm). All eyes showed decrease of serous detachment of the neurosensory retina (not present in 7/9 cases at 1 month). Intraretinal central cyst resolved in 7/9 cases; small peripheral cysts were persistent in only 2/9 cases. Spectral domain optical coherence tomography demonstrated the presence and the integrity of external limiting membrane and inner and outer segments (IS/OS) of the photoreceptors in 6/9 cases at month 3. Forty percent of patients gained = 10 letters of best-corrected visual acuity at 3 months. The safety profile was consistent with the results of a previous phase III trial of Ozurdex®, and no serious ocular or systemic adverse events were observed during the follow-up period. CONCLUSIONS: In patients with macular edema in retinal vein occlusion, sustained-release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option to control macular edema. At the final visit, foveal thickness was decreased to physiologic levels in all eyes. In parallel with resolution of the macular edema, visual acuity was significantly improved at the final visit. However, final visual acuity in eyes with still interrupted or thickened IS/OS interface was significantly poorer than that in eyes with a normal IS/OS line.

Hemodilution therapy using automated erythrocytapheresis in central retinal vein occlusion: results of a multicenter randomized controlled study.

BACKGROUND: Central retinal vein occlusion (CRVO) leads to poor visual outcome in most eyes. Abnormal hemorheology was suspected to play a major role in its pathogenesis. CRVO treatment is still a matter of debate but several studies have pointed out the efficacy of isovolumic hemodilution. The aim of this study was to assess the feasibility and efficacy of hemodilution using automated erythrocytapheresis in recent-onset CRVO. METHODS: In this prospective randomized controlled multicenter study, 61 consecutive CRVO patients were enrolled when they met the following criteria: CRVO lasting for 3 weeks or less, visual acuity ranging from 20/200 to 20/32, age between 18 and 85 years, no diabetes, no uncontrolled systemic hypertension, no antiplatelet or anticoagulant therapy, hematocrit higher than 38%, and signed informed consent. Patients were randomly assigned to the hemodilution group (n = 31) or to the control group (n = 30). Hemodilution therapy consisted of one session of erythrocytapheresis on outpatient basis, followed by additional session(s) for 6 weeks if needed. Target hematocrit was 35%. Follow-up was 12 months. RESULTS: No statistical differences in age, associated risk factors, or CRVO characteristics were observed at baseline between both groups. Mean visual acuity was equivalent to 20/80 in the hemodilution group and to 20/63 in the control group (non-significant difference). In the treated group, mean number of hemodilution sessions was 3.3 (range, 1 to 6), and no major side-effects occurred. At the 12-month follow-up visit, 64.5% of the hemodilution group had visual acuity of 20/40 or better compared to 40% of the control group (p = .048). Visual change was a gain of 1.7 ETDRS line in the hemodilution group versus a loss of 2.3 lines in the control group (p = .007). There was less conversion into an ischemic form in the hemodilution group (11%) than in the control group (50%, p = .004). Mean final retinal thickness was 289 µm in the hemodilution group versus 401 µm in the control group (p = .068). CONCLUSIONS: This multicenter controlled randomized study demonstrated that automated erythrocytapheresis is a safe and effective tool for performing hemodilution and confirmed that hemodilution therapy can improve the final prognosis of CRVO when applied in the early phase of the disease.

Steroids and macular edema from retinal vein occlusion.

PURPOSE: The possibility of applying long-lasting steroids, such as triamcinolone and subsequently dexamethasone implant, directly in the eye, without the systemic side effects observed after their oral or intravenous administration, aroused great enthusiasm among ophthalmologists. METHODS AND RESULTS: The SCORE study, a multicenter clinical trial, compared the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation in central retinal vein occlusion (CRVO) participants with macular edema secondary to perfused CRVO. This study marked a turning point in the management of retinal vein occlusion (RVO), since it was the first report on an effective treatment of macular edema due to CRVO. But in branch retinal vein occlusion (BRVO), the SCORE study showed no difference in visual acuity for the standard care group compared with the triamcinolone groups; however, the rates of adverse events (particularly elevated intraocular pressure and cataract) were highest in the 4-mg group. The authors concluded that laser grid photocoagulation should remain the benchmark against which other treatments should be compared. The Geneva Study, a randomized, controlled, clinical trial, conducted to evaluate the safety and efficacy of an intravitreal implant that delivers sustained levels of dexamethasone (Ozurdex™), studied the largest group of RVO patients with macular edema (1267 patients), including 35% CRVO and 65% BRVO. The study demonstrated that this slow-release device could both reduce the risk of vision loss and improve the speed and incidence of visual improvement in eyes with macular edema secondary to CRVO and BRVO, with fewer side effects, such as elevation of intraocular pressure or cataract. Other ongoing studies evaluate the safety and efficacy of anti-vascular endothelial growth factor injection; preliminary results showed that these therapies are effective in decreasing macular edema and improving visual acuity, with fewer ocular adverse effects, but their duration of action seems limited. CONCLUSIONS: These recent studies result in a great change in the management of macular edema from RVO. Unfortunately, long-term studies on safety and efficacy are not yet available, and further studies will have to show whether the short-term benefits are only transient or may finally lead to a long-lasting improvement in vision.

Retinal vein occlusions.

Retinal vein occlusions (RVOs) have been defined as retinal vascular disorders characterized by dilatation of the retinal veins with retinal and subretinal hemorrhages and macular edema, and/or retinal ischemia. Fluorescein angiography (FA) remains essential for the diagnosis and prognosis of RVO, allowing recognition of the diverse types of RVO, such as perfused or nonperfused, as well as detection of the different modalities in natural history. F A is the most effective method to determine the presence (or absence) of macular cystoid edema, its extension, persistence, regression, or the degree of ischemia. Spectral domain optical coherence tomography (SD-OCT) helps to quantify the changes in retinal thickness, the amount of cystoid macular edema, and supplies additional information, such as whether the accumulated fluid is located mostly within the retinal layers or additionally in the sub retinal space. SD-OCT can display the presence and integrity of the outer limiting membrane and of the inner and outer segments of the photoreceptors, useful information for prognosis and a guide for treatment in the management of RVO. Laser photocoagulation in a 'grid' pattern over the area, demonstrated as leaking by FA, remains the 'reference treatment for macular edema due to branch retinal vein occlusion', according to the recent results of the SCORE Trial. Recent case series studies and prospective randomized trials strongly suggest an antiedematous effect of intravitreal steroids and an associated improvement in vision. These studies have suggested that intravitreal steroids (triamcinolone, fluocinolone, dexamethasone in a slow-release device) and intravitreal anti-VEGF drugs (bevacizumab, ranibizumab, pegabtanib) may at least temporarily reduce foveal edema and correspondingly improve visual function. Surgical treatment modalities have been reported for RVOs. The positive action of vitrectomy seems durable; the combination of surgery and intravitreal injection of steroids and/or an injection of tissue plasminogen activator could permit a more rapid and lasting action. However, strong data from randomized trials are warranted.

Intravitreal ranibizumab for choroidal neovascularization complicating pathologic myopia.

PURPOSE: The purpose of this study was to evaluate the efficacy of intravitreal injections of ranibizumab in choroidal neovascularization secondary to pathologic myopia. METHODS: A prospective case series of 32 eyes of 32 patients affected with choroidal neovascularization secondary to pathologic myopia treated by intravitreal injections of ranibizumab. Best-corrected visual acuity, fundus examination, fluorescein angiography, indocyanine green angiography, and spectral domain-optical coherence tomography were performed for the diagnosis of myopic choroidal neovascularization. Best-corrected visual acuity and central retinal thickness measurement were performed monthly during the follow-up. RESULTS: The median number of injections was 3 with a median follow-up of 17 months. The median visual acuity at baseline was 20/100 and improved to 20/50 at final examination (P < 0.0001). Best-corrected visual acuity improved by > or = 3 lines in 15 of 32 eyes (46.8%). The median central thickness was 336 microm (range, 179-663 microm) at baseline and 233 microm (range, 125-465 microm) at final examination (P < 0.0001). No severe drug-related side effect was reported. CONCLUSION: In our series of myopic choroidal neovascularization, intravitreal injections of ranibizumab showed visual acuity improvement and retinal thickness reduction. Further prospective multicentric clinical trials are needed to evaluate the safety and the efficacy of this treatment.

Redistribution of the neurosensory retina in inferior limited macular translocation: an evaluation using image registration.

BACKGROUND: The present work aims to demonstrate the role of redistribution of the neurosensory retina (RNR)-that is, retinal tissue stretching and compression-in inferior limited macular translocation (LMT), to perform displacement mapping all over the area centralis, and to try and improve displacement evaluation precision. METHODS: Using piecewise linear image registration (through Matlab) on indocyanine green angiographic frames, we have evaluated the deformation (on both the retinal and choroido-scleral layer) of a pre-operative grid superimposed on the area centralis, plotted displacement vectors all over the area centralis, and calculated a scale ratio between pre- and post-operative frames. The scale ratio tests whether or not the same physical distance is represented by the same distance on these frames. RESULTS: The choroido-scleral layer is not deformed following surgery. The retinal layer shows areas of stretching and compression, demonstrating the RNR. Displacement vectors feature a rotating pattern around the optic disk (except if a macular fold exists) and a positive naso-temporal gradient. The median scale ratio is 3.8% (2.5% to 5.8%). CONCLUSIONS: LMT involves RNR accounting for inferior retinal displacement, despite the supposedly limited internal scleral shortening. Our study confirms that the optic disk temporal edge is the displacement axis (except if a macular fold exists). Our method, unaffected by a non-zero scale ratio, provides more precision than previously published.

Clinical evaluation of the use of indocyanine green for peeling the internal limiting membrane in macular hole surgery.

BACKGROUND: To evaluate the role of indocyanine green (infracyanine) in macular hole surgery. METHODS: A retrospective review of 38 consecutive eyes with macular hole, operated on with internal limiting membrane peeling (ILM), using or not using infracyanine (ICG), diluted in glucose 5% and filtered. Anatomical and functional results were analysed in each group, using visual field testing, fluorescein fundus angiography and particularly blue filter fundus photographs for the detection of retinal pigment epithelial changes and lesions of optic nerve fibres layer. RESULTS: Fifteen eyes underwent surgery without ICG and 23 eyes with ICG. The mean period of follow-up was 10 months. The duration of surgery was significantly lower in the group with ICG than without (P < 0.001). Overall, 84% of the holes closed without difference between both groups. The improvement in vision at 1, 6 and 12 months was similar in both groups. Fewer defects in the optic nerve fibres layer were observed in the group with ICG than without (P = 0.02). Staining with ICG revealed the presence of an associated epiretinal membrane in 61% of eyes, whereas it was clinically visible in only 17.5% before surgery. CONCLUSION: Using ICG for ILM peeling produced similar visual results to those obtained without ICG. It reduced significantly the duration of surgery and the trauma to the optic nerve fibres layer, without increasing the risk of retinal pigment epithelial damage. However, in the light of recent reports about the possible toxicity of ICG, its use should be restricted in clinical practice to difficult cases.