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.

VITRECTOMY RESULTS FOR RHEGMATOGENOUS RETINAL DETACHMENT WITH CONCOMITANT MACULAR HOLE IN NONMYOPIC PATIENTS.

PURPOSE: To report on results of pars plana vitrectomy with ILM peeling in patients with rhegmatogenous retinal detachment (RRD) and concomitant macular hole (MH) and to assess for preoperative associated conditions related to this type of RRD. METHODS: Patients undergoing surgical repair for RRD between 2014 and 2021 were reviewed, and subjects with concomitant, non-causal, macular hole were identified. We studied post-operative macular status, retinal reattachment rate and visual acuity. RESULTS: Over 532 eyes operated on for RRD, 11 (2.06%) had a concurrent non-causal macular hole. Preoperative PVR B or superior was recorded in 86 eyes (16.6%) of the entire cohort and in 6 eyes (54.54 %) with RRD and concomitant MH (p=0.00001). Severe hypotony with choroidal detachment was present in 15 eyes (2.81%) of the entire cohort and in 3 eyes (27.27%) with RRD and concomitant MH (p=<0.00001). CONCLUSIONS: RRD with concomitant MH is an infrequent association. Retinal reattachment and anatomical hole closure can be achieved in most of cases but despite this fact, functional recovery is usually not good. Preoperative PVR is a more frequent finding in this group of patients, as well as severe hypotony with choroidal detachment.

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.

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.

NONPERFUSION ASSESSMENT IN RETINAL VEIN OCCLUSION: Comparison Between Ultra-widefield Fluorescein Angiography and Widefield Optical Coherence Tomography Angiography.

PURPOSE: To compare widefield optical coherence tomography angiography (OCTA) to ultra-widefield fluorescein angiography (UWFA) in the assessment of nonperfusion in retinal vein occlusion (RVO). METHODS: A cross-sectional study of 43 eyes of 43 patients with RVO examined using both widefield OCTA (PLEX Elite, Carl Zeiss Meditec, Dublin, CA) with a panoramic montage of five 12 × 12-mm images and UWFA (Optos, 200°). Qualitative analysis was performed according to nonperfusion areas (cutoff: three disk areas) on widefield OCTA. The quantitative analysis assessed the vascular density on the widefield OCTA and ischemic index on UWFA. RESULTS: The ischemic index on UWFA and vascular density in the superficial and deep plexus correlated significantly (P = 0.019, r = 0.357 and P < 0.013, r = 0.375, respectively). The qualitative classification on widefield OCTA and ischemic index on UWFA correlated significantly (P < 0.001, r = 0.618). For the detection of marked nonperfusion (ischemic index ≥ 25%), widefield OCTA had a sensitivity of 100% and a specificity of 64.9%. CONCLUSION: The presence of nonperfusion on UWFA correlated with widefield OCTA. Optical coherence tomography angiography could help to identify high-risk RVO patients who might benefit from a further evaluation using fluorescein angiography.

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.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN RETINAL VEIN OCCLUSION: Correlations Between Macular Vascular Density, Visual Acuity, and Peripheral Nonperfusion Area on Fluorescein Angiography.

PURPOSE: To study correlations in patients with retinal vein occlusion between the automatically quantified macular vascular densities in the superficial and deep capillary plexus (DCP) obtained using optical coherence tomography angiography (OCTA) and the data from conventional examination, particularly visual acuity and peripheral retinal nonperfusion assessed using fluorescein angiography (FA). METHODS: Retrospective, observational study of patients with retinal vein occlusion who underwent a comprehensive ophthalmic examination including FA and OCTA using the AngioVue OCTA system version 2015.100.0.35 (OptovueRTVue XR 100; AVANTI, Inc, Fremont, CA). Vascular densities in the superficial capillary plexus and DCP, as well as the area of the foveal avascular zone, were measured using the AngioAnalytics software. RESULTS: Our study of 65 eyes of 61 patients (33 men, mean age: 67 years) showed a significant correlation between peripheral nonperfusion on FA and (1) automatically quantified global vascular density in both plexus (P = 0.021 for the DCP) and (2) foveal avascular zone area (P = 0.037). We also found significant correlations between capillary dropouts in both plexus and peripheral nonperfusion (P < 0.001 for both) and between visual acuity and vascular densities (P = 0.002 for the global density in the DCP). Global density less than 46% in the DCP was associated to the presence of peripheral nonperfusion area on FA (P = 0.003) and to enlargement of the superficial foveal avascular zone (P = 0.002). CONCLUSION: Our study demonstrated a significant correlation between automatically quantified macular vascular density on OCTA and peripheral nonperfusion on FA; OCTA could help identify high-risk retinal vein occlusion patients who may benefit from further evaluation using FA.

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.

En face enhanced depth imaging optical coherence tomography features in adult onset foveomacular vitelliform dystrophy.

BACKGROUND: Our purpose was to describe the different morphological features in adult onset foveomacular vitelliform dystrophy (AOFVD), using en face enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). METHODS: Thirty eyes of 22 consecutive patients presenting with diagnosis of AOFVD were enrolled. Diagnosis of AOFVD was concluded based on fundus examination, autofluorescence imaging, fluorescein angiography and SD-OCT. En face OCT imaging was obtained with the Spectralis EDI SD-OCT; 97 inverted sections (nine averaged B-scans per image) were acquired. RESULTS: On en face OCT, vitelliform lesions appeared as regular concentric rings of different reflectivity. From the periphery to center of the ring, we observed: (1) the hypereflective ring representing the inner segment/ outer segment (IS/OS) junction, which was continuous in 23 out of 30 eyes, and (2) a well-detectable hyporeflective ring between the IS/OS junction and vitelliform material in 20 out of 30 eyes; the innermost composant of the lesion was hypereflective, and it corresponded to vitelliform material. In eight out of 30 eyes, a hyporeflective "croissant"-shaped lesion with inferior concavity in the upper part of the hyperreflective material was present. Hypereflective retinal pigment epithelium (RPE) elevations or bumps were detected in 25 out of 30 eyes. These areas of focal RPE thickening or bumps appeared to be intensely hypereflective on infrared reflectance imaging. CONCLUSION: En face imaging of the retina helps visualizing the distribution of vitelliform material in AOFVD. The sedimentation of vitelliform lesions is characterized by a upper "croissant"-shaped hypoflectivity. The bumps/thickening of RPE appeared as hypereflective lesions on IR imaging.

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.

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.

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.

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.

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.

Biomarkers of Peripheral Nonperfusion in Retinal Venous Occlusions Using Optical Coherence Tomography Angiography.

PURPOSE: To study the association between the assessment of central macular vascular layers by optical coherence tomography angiography (OCT-A) and peripheral nonperfusion evaluated by fluorescein angiography (FA) in patients with retinal venous occlusion (RVO). METHODS: Retrospective review of RVO patients without macular edema. Patients underwent a comprehensive ophthalmic examination including FA, spectral-domain OCT, and OCT-A. Significant ischemia was defined as nonperfusion areas superior or equal to the equivalent of one retinal quadrant on FA. Vascular density (VD) and foveal avascular zone were measured using AngioAnalytics software. Fractal dimension (FD) and lacunarity (LAC) were computed using an algorithm designed by MATLAB (MathWorks, Natick, MA). These variables were used to build a model that translates their association with OCT-A parameters. RESULTS: There were 48 eyes (48 patients) of which 19 had significant peripheral nonperfusion. Deep capillary plexus FD, VD, and LAC were associated with significant ischemia. In fact, regarding the association with this outcome, LAC alone had the highest area under the curve (AUC = 0.88) followed by FD (AUC = 0.85) and VD (AUC = 0.73). The multivariable model that included LAC and VD, adjusted by best-corrected visual acuity (BCVA) achieved the best performance for the identification of severe nonperfusion on wide-field FA (AUC = 0.93). CONCLUSIONS: The characteristics of the central macular deep capillary plexus on OCT-A may be associated with peripheral nonperfusion on FA, particularly the combination of LAC and vessel density after adjusting by BCVA. TRANSLATIONAL RELEVANCE: Fractal-based metrics applied to OCT-A may become a valuable marker of ischemia in RVO and help guide the clinical decision to perform invasive angiography.

Extended Injection Intervals after Switching from Ranibizumab to Aflibercept in Macular Edema due to Central Retinal Vein Occlusion.

PURPOSE: To assess treatment interval extension after switching from ranibizumab to aflibercept intravitreal injections in macular edema (ME) due to central retinal vein occlusion (CRVO) with an insufficient response or frequent recurrences to initial treatment. METHODS: CRVO eyes treated with ranibizumab injections on a treat-and-extend (TAE) basis with an insufficient response or frequent recurrences were switched to aflibercept. Primary endpoint was the change in injection intervals before and after the switch. RESULTS: Eleven eyes were included in this retrospective bicentric study. Before switching, patients received a mean number of 15.3 ranibizumab injections (range, 6-34) during a mean follow-up of 23.4 months (range, 6-57). After switching to aflibercept, patients received a mean number of 12.4 injections (range, 6-20) during a mean follow-up of 25.5 months (range, 16-38). Treatment interval could be extended from 6.1 (range, 4-8) to 11 weeks (range, 8-16) (p=0.001) corresponding to a mean extension of injection interval of +4.9 weeks. CONCLUSION: In case of insufficient response or frequent recurrences of ME due to CRVO in patients treated with ranibizumab on a TAE basis, switching to aflibercept could allow extending treatment intervals, which could reduce the injection burden for these patients.

Photodynamic therapy vs limited macular translocation in the management of subfoveal choroidal neovascularization in pathologic myopia: a two-year study.

PURPOSE: To compare the results of limited macular translocation and photodynamic therapy (PDT) in subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia with a 24-month follow-up. DESIGN: Retrospective analysis of nonrandomized interventional clinical study. METHODS: Retrospective review of 66 consecutive patients: 34 myopic eyes with subfoveal neovascularization treated by PDT and 32 operated on with the translocation technique. Translocation was considered principally when the lesion size was adequate (nasal inferior margin of the membrane less than half a disk diameter away from the center of the fovea) with duration of symptoms of less than four months. Main outcome measure was the postoperative change in visual acuity. RESULTS: In the translocation group, mean gain in visual acuity was greater than in the PDT group (+2.8 lines and -1.8 line, respectively, P = .001). In the translocation group, 55% of eyes gained 3 lines or more at two years compared with 10% in the PDT group. Sixty percent of eyes in the translocation group vs 40% in the PDT group had an improvement of at least five letters. Mean foveal displacement after translocation was 906 mum; postoperative complications included retinal detachment (three eyes), macular fold (one eye), and transient diplopia (four eyes). In young patients, the postoperative gain was better in both groups. In the translocation group, mean survival time for choroidal neovascularization recurrence was 40 months for patients younger than 40 years and 20 months for older patients. CONCLUSIONS: Translocation showed better results than PDT at two years. Further studies are required to confirm these findings.

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.

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.