Louis K. Chang

Prospective Study of Intravitreal Ranibizumab as a Treatment for Decreased Visual Acuity Secondary to Central Retinal Vein Occlusion

PURPOSE To evaluate intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity (VA) secondary to central retinal vein occlusion (CRVO). DESIGN Prospective, interventional case series. METHODS Patients with CRVO prospectively recruited from a practice were administered intravitreal ranibizumab 0.5 mg (Lucentis; Genentech Inc, South San Francisco, California, USA) at baseline and monthly for two additional doses. The patients were given additional ranibizumab if they had macular edema as determined by optical coherence tomography or any new intraretinal hemorrhage. Patients were evaluated for number of required injections, side effects, changes in VA, and macular thickness. RESULTS There were 20 eyes of 20 patients who at baseline had a mean age of 72.1 years, a mean VA of 45.8 Early Treatment of Diabetic Retinopathy letters, and a mean central macular thickness of 574.6 microm. Of the 20 eyes, five previously had received intravitreal triamcinolone and 11 had received intravitreal bevacizumab (Avastin; Genentech Inc). At 12 months of follow-up, the mean VA improved to 64.3 letters and the central macular thickness decreased to 186 microm (both different than baseline values; P < .001) using a mean of 8.5 injections. The change in macular thickness was not correlated with the change in VA. In one patient with a history of transient ischemic attack, an ischemic stroke developed but no sequela resulted. In another patient, vitreomacular traction developed, but the patient had improved acuity as compared with baseline. There were no infections, retinal tears, or detachments. CONCLUSIONS Intravitreal ranibizumab used over a period of one year improved mean VA, with low rates of adverse events, in patients with CRVO.

Tears Of The Retinal Pigment Epithelium: An Old Problem in a New Era

Background/Purpose: Recent attention has focused upon several reports of retinal pigment epithelium (RPE) tears following vascular endothelial growth factor (VEGF)–modulating therapy. The authors review the clinical features, etiologies, imaging characteristics, and pathogenesis of RPE tears and their relationship with intravitreal anti-VEGF treatments. Methods: The authors conducted a comprehensive literature search of RPE tears or rips of any etiology using the PubMed database. They have also included a retrospective analysis of an additional five cases of RPE tears following anti-VEGF therapy, four after bevacizumab and one after ranibizumab. Results: Thirty-three cases of RPE tear after treatment with pegaptanib, bevacizumab, or ranibizumab have been previously reported in the literature. The authors have collected and analyzed the clinical features for 25 of these cases for which this information was available. The authors have also included analysis of an additional five cases. Common features of each of these 30 cases included advanced age of the patient, the presence of fibrovascular pigment epithelial detachment (PED) or PED associated with choroidal neovascularization (CNV), and diagnosis of the tear within 4 to 8 weeks of the first or second injection. Conclusions: RPE tears may develop during the course of anti-VEGF therapy for age-related macular degeneration–related PED. Patients with high-risk lesions, especially large irregular PED associated with CNV, should be counseled and monitored for this complication, which may limit visual prognosis.

Disruption of the photoreceptor inner segment-outer segment junction in eyes with macular holes.

Purpose: To examine the relationship between visual acuity and morphologic characteristics of macular holes as determined using spectral domain optical coherence tomography (SD OCT). Methods: A retrospective analysis was performed of eyes with open and closed macular holes at a single, referral-based retina practice. The main outcome measures included best-corrected Snellen visual acuity and SD OCT findings, including the size of the macular hole and the disruption of the junction between inner segments (ISs) and outer segments (OSs) of the photoreceptors. Results: The mean visual acuity for eyes with open (n = 24) and closed (n = 17) macular holes was 20/166 (range, 5/400 to 20/40) and 20/39 (range, 20/80 to 20/25), respectively. The mean macular hole diameter was 859 &mgr;m. A disruption of the IS–OS junction was observed in all eyes, and this disruption had a mean diameter of 1,947 &mgr;m in eyes with an open macular hole and 626 &mgr;m in those with a closed macular hole. There was a negative correlation between both the size of the macular hole (P < 0.001) and the IS–OS disruption (P = 0.01) and visual acuity in eyes with open macular holes. In eyes with closed macular hole, the size of the IS–OS disruption was not correlated with visual acuity (P = 0.82). Conclusions: The photoreceptor layer appears to be involved for a much larger area than that occupied by the macular hole itself. The abnormality in the IS–OS boundary line may reflect perturbation of a higher level of retinal organization and not an absolute loss of photoreceptor OSs.

Ultrastructural Correlation of Spectral-Domain Optical Coherence Tomographic Findings in Vitreomacular Traction Syndrome

PURPOSE To examine the ultrastructural correlates of spectral-domain optical coherence tomography (SD-OCT) findings in patients with vitreomacular traction (VMT). DESIGN Observational case series. METHODS Retrospective analysis of six eyes of consecutive patients who underwent vitrectomy surgery for VMT was performed in this single-center, noncomparative study. One patient had a concurrent macular hole. Preoperative assessment included SD-OCT examination with 3-dimensional image reconstruction. During surgery the vitreous cone was dissected from the vitreous body using scissors, then removed from the surface of the retina with a combination of sharp dissection and peeling, and subsequently submitted for histologic and transmission electron microscopic processing. RESULTS SD-OCT showed prominent vitreal-foveal adhesion in all six eyes. Each eye had an epiretinal membrane (ERM) under the detached perifoveal posterior vitreous detachment. In all eyes this ERM appeared to course up the cone of attached vitreous and along the back surface of the posterior vitreous face. Ultrastructural analysis showed fibrocellular proliferations in the vitreous specimens in all six cases, which included retinal pigment epithelium (RPE) cells (five eyes), fibrocytes (four eyes), and macrophages (three eyes). CONCLUSIONS The adhesion between the vitreous and fovea in vitreomacular traction syndrome is accompanied by fibrocellular proliferation along the exposed surfaces of the inner retina and the posterior surface of the vitreous. This fibrocellular proliferation may augment the adhesion between the vitreous and fovea, and may account for the prominent OCT signal seen along the posterior surface of the vitreous in these cases.

Predictors Of Anti-vegf-associated Retinal Pigment Epithelial Tear Using Fa And Oct Analysis

Purpose: To identify fluorescein angiography and optical coherence tomography (OCT) predictors for retinal pigment epithelial (RPE) tear in eyes with pigment epithelium detachment (PED) associated with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor (VEGF) modulating therapy. Design: Retrospective comparative case series. Methods: In a single institutional center, 60 consecutive patients with PED and neovascular age-related macular degeneration treated with VEGF modulating therapy (either pegaptanib, bevacizumab, or ranibizumab) for more than a 27-month period were included in the study. Fluorescein angiography (FA) and OCT imaging was performed before and after anti-VEGF therapy. Formal statistical analysis comparing the tear group to the nontear group was performed to identify high-risk features for RPE tear. Results: RPE tear rate for eyes with vascularized PED receiving anti-VEGF therapy was 17% (10/60). There were highly statistically significant differences in the median PED size on fluorescein angiography (greatest linear diameter) (3.2 mm versus 1.8 mm, respectively; P < 0.001) and in the median maximum PED height on OCT (394 &mgr;m versus 149 &mgr;m, respectively; P = 0.001) between the tear group and nontear group. There was also a significant difference in terms of the presence of subretinal fluid on OCT between the two groups (87.5% versus 39%, respectively; P = 0.019). Conclusion: Large PED basal diameter and vertical height are correlated with an increased risk of developing an RPE tear after anti-VEGF therapy. Patients with large vascularized PED by fluorescein angiography and/or OCT analysis should be alerted of the risk for vision loss due to RPE tear after anti-VEGF therapy.

Bevacizumab Treatment for Subfoveal Choroidal Neovascularization From Causes Other Than Age-Related Macular Degeneration

OBJECTIVE To report the results of intravitreous bevacizumab (Avastin) treatment for choroidal neovascularization (CNV) from causes other than age-related macular degeneration (AMD). METHODS We performed a retrospective analysis of eyes that received intravitreous bevacizumab, 1.25 mg, for subfoveal non-AMD CNV at a referral-based retinal practice. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. The main outcome measure was visual acuity (VA). RESULTS The study included 39 eyes of 36 patients with subfoveal CNV secondary to multifocal choroiditis (n = 12), angioid streaks (n = 11), myopic degeneration (n = 10), idiopathic disease (n = 4), or other disease (n = 2). The median baseline VA was 20/60 (logMAR, 0.48). The mean follow-up was 58.8 weeks, and the mean number of injections per eye was 3.4. After 3-month follow-up, the median VA was 20/30 (logMAR, 0.18) (P = .004 vs baseline). At last follow-up, the median VA was 20/40 (logMAR, 0.30). This remained an improvement compared with baseline (P < .02) but was worse than 3-month follow-up (P < .03). There was no correlation between underlying diagnosis and VA change during follow-up. CONCLUSION Subfoveal CNV secondary to non-AMD causes treated with intravitreous bevacizumab responded favorably and similarly, despite varying underlying etiologies.

Surgical outcomes after massive subretinal hemorrhage secondary to age-related macular degeneration.

Purpose: Massive subretinal hemorrhage (SRH), defined as a thick submacular bleed that extends past the equator in at least two quadrants, is a rare sequela of age-related macular degeneration. This report describes outcomes after surgical intervention for massive SRH. Methods: The study design is a retrospective interventional case series. Records of consecutive patients who underwent surgical intervention for massive SRH were reviewed. Outcomes included change from baseline in postoperative acuity at Months 1, 3, 6, 9, and 12 and postoperative complications. Results: Fifteen consecutive eyes of 13 patients who underwent surgery for massive SRH were included. Procedures performed on initial surgery included subretinal instillation of 25 μg/0.1 mL tissue plasminogen activator (15 of 15), gas tamponade (12 of 15), oil tamponade (3 of 15), 180° or greater retinotomy (4 of 15), and/or cataract extraction (2 of 15). Patients were followed for a median of 20 months (range, 3-66 months). The median visual acuity at baseline and postoperative Month 1 was hand motions but improved to counting fingers at postoperative Months 3 (P = 0.04), 6 (P = 0.04), 9 (P = 0.04), and 12 (P = 0.10). Of the 15 eyes, 9 required at least 1 additional procedure for an indication of hyphema and/or vitreous hemorrhage (n = 6), retinal detachment (n = 2), glaucoma (n = 1), cataract (n = 1), and aphakia (n = 1). At the time of the onset of SRH, 5 of 13 patients were anticoagulated with warfarin (4 patients) or clopidogrel (1 patient), and 1 was diagnosed with a coagulopathy, factor XI deficiency. Conclusion: Massive SRH related to age-related macular degeneration has a grave prognosis. Risk factors may include anticoagulation and coagulopathy. Limitations of the study include its retrospective nature, small sample size, imprecision in acuity measurements below 20/400, and lack of a control group. In this series, surgical intervention was associated with a modest improvement in median visual acuity up to 1 year postoperatively.

Longer-term Outcomes Of A Prospective Study Of Intravitreal Ranibizumab As A Treatment For Decreased Visual Acuity Secondary To Central Retinal Vein Occlusion

Purpose: To evaluate long-term effectiveness and safety of intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity secondary to central retinal vein occlusion. Methods: In this prospective interventional case series, patients with central retinal vein occlusion were administered intravitreal ranibizumab 0.5 mg at baseline and monthly for 2 additional doses. Thereafter, the patients were given additional ranibizumab if they had macular edema by optical coherence tomography, leakage during fluorescein angiography, or any intraretinal hemorrhage. Results: There were 35 eyes of 35 patients who at baseline had a mean visual acuity of 44.2 Early Treatment Diabetic Retinopathy Study letters and a mean central macular thickness of 638 μm. At 12 months, mean visual acuity of 32 eyes improved by 16.5 letters and macular thickness decreased to 164 μm (P < 0.001 vs. baseline for each). At 24 months, mean visual acuity of 24 eyes improved by 17.8 letters and macular thickness was 263 μm (P < 0.001 vs. baseline for each). Patients received an average of 10.2 injections during the first year and 6.6 injections during the second year. No cases of endophthalmitis, retinal detachment, or neovascularization were observed. Conclusion: Intravitreal ranibizumab caused a significant improvement in visual acuity and central retinal thickness, which persisted for up to 2 years with minimal side effects.

Optic disk pit morphology and retinal detachment: optical coherence tomography with intraoperative correlation.

Background: The pathogenesis of optic nerve head pits and associated retinal detachment, and the most effective surgical intervention when visual loss develops, remains unclear. Methods: The morphology of the optic disk in patients with pits was investigated with optical coherence tomography. For those who underwent surgical treatment for pit-associated retinal detachment, the efficacy of treatment by vitrectomy and separation of the posterior hyaloid, with and without additional peeling of peripapillary tissue, was assessed. Results: On optical coherence tomography imaging, 14 of 18 pits (78%) demonstrated a localized pit-like invagination, whereas 3 (17%) had disks with a generally excavated structure. For 16 of 18 pits (89%), there was evidence of condensed vitreous or glial tissue seen extending from the pit or inside the optic disk. Nine eyes with retinal detachment underwent vitrectomy, posterior hyaloid separation, and endolaser. The retinal detachment completely resolved in 6 of 6 cases where the surgeon additionally peeled the fibrous tissue from the pit and 2 of 3 cases where this was not performed. Conclusion: Spectral domain optical coherence tomography demonstrates the varying morphology of optic pit anatomy. Condensed vitreous strands or glial tissue in the optic nerve pit may also contribute to retinal detachment development.

PROSPECTIVE EVALUATION OF A SUSTAINED-RELEASE DEXAMETHASONE INTRAVITREAL IMPLANT FOR CYSTOID MACULAR EDEMA IN QUIESCENT UVEITIS.

Purpose: To investigate dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc) in the treatment of uveitic cystoid macular edema that had persisted in the absence of intraocular inflammation. Methods: In this prospective interventional case series, 10 patients with uveitic cystoid macular edema and quiescent uveitis were treated with dexamethasone intravitreal implant at baseline and evaluated monthly for one year. Patients were retreated whenever cystoid macular edema recurred. The primary outcome measure was best-corrected visual acuity (BCVA) at day 90. Results: At day 90, mean improvement from baseline BCVA was 14.4 letters (P = 0.0003), 70% of patients had a ≥10 letter BCVA improvement, 50% of patients had a ≥15 letter BCVA improvement, and the mean decrease from baseline central subfield retinal thickness was 140 &mgr;m (P = 0.008). Improvements were maintained through day 360 with retreatment as needed. At day 360, mean improvement in BCVA was 16.5 letters (P = 0.006) and the mean decrease in central subfield retinal thickness was 158 &mgr;m (P = 0.002). One patient experienced intraocular pressure >25 mmHg (managed with topical medication). Two phakic patients (2/8; 25%) had worsening of lens opacity requiring cataract extraction. Conclusion: Dexamethasone intravitreal implant may be an effective treatment for patients with persistent cystoid macular edema in quiescent uveitis.