Tien P. Wong

Ranibizumab In Preproliferative (ischemic) Central Retinal Vein Occlusion: The Rubeosis Anti-vegf (rave) Trial

Purpose: To analyze the efficacy and safety of ranibizumab in eyes with preproliferative (ischemic) central retinal vein occlusion. Methods: In this prospective, phase I/II, open-label clinical trial, eyes at high risk of neovascular complications were identified; all eyes met ≥3 of 4 high-risk criteria: 1) the best-corrected visual acuity being ⩽20/200, 2) loss of the 1-2e isopter on Goldmann visual field, 3) relative afferent pupillary defect being ≥0.9 log units, and 4) electroretinogram B-wave reduction to ⩽60% of the corresponding A-wave. Monthly intravitreal ranibizumab treatment for 9 months, monthly monitoring for 3 months, and then monthly examination with pro re nata retreatment on evidence of disease activity for 24 months were performed. Therefore, the total study duration was 36 months. Results: The main outcome measures were mean change in the best-corrected visual acuity and central macular thickness by optical coherence tomography, proportion of patients with neovascular complications, and the incidence and severity of ocular and nonocular adverse events. Twenty patients were enrolled in the Rubeosis Anti-VEgf trial, and the mean number of intravitreal treatments administered through Months 24 and 36 were 14.1 and 17.2, respectively. The mean best-corrected visual acuity letters gained were +21.1 and +21.4 at 9 and 36 months, respectively. The mean central macular thickness improved −294 &mgr;m from baseline after 9 monthly treatments. Subsequently, after 3 months of observation, the mean central macular thickness increased +203 &mgr;m. On initiation of pro re nata ranibizumab retreatment, the mean central macular thickness then improved −191 &mgr;m at Month 36 compared with Month 12. Nine patients developed neovascular complications, being diagnosed after a mean of 24-month follow-up (range, 3–44 months), with 2 patients developing neovascularization after completion of the 36-month trial endpoint (at Months 42 and 44 after study enrollment). Conclusion: Intravitreal ranibizumab therapy can improve retinal anatomy and vision in eyes with severe central retinal vein occlusion. Despite significant clinical benefit with antivascular endothelial growth factor therapy, the risk of neovascular complications was not ameliorated by vascular endothelial growth factor blockade, but was merely delayed.

Progressive retinal nonperfusion in ischemic central retinal vein occlusion.

Background: Serial wide-field fluorescein angiography was performed on eyes with preproliferative (ischemic) central retinal vein occlusion to evaluate retinal perfusion. Methods: Serial wide-field fluorescein angiography was performed on 12 preproliferative central retinal vein occlusion eyes in the 3-year Rubeosis Anti-VEGF (RAVE) trial using the Staurenghi lens (Ocular Staurenghi 230SLO Retina Lens) with a scanning laser ophthalmoscope (Heidelberg HRA Spectralis). “Disk area” was defined anatomically for each eye. Results: Mean total field of gradable retina was 290 disk areas (range, 178–452). All eyes demonstrated extensive areas of retinal nonperfusion; at baseline, mean area of retinal perfusion was 106 disk areas (range, 37–129), correlating with a mean of 46.5% perfused retinal area (range, 19.1–56.4%). The area of retinal nonperfusion increased in all eyes with a mean loss of approximately 8.1% of perfused retinal area per year (range, 4.3–12.4%), which corresponded to a mean 15-disk areas (range, 12–35) of retina evolving from perfused to nonperfused annually. The extent of baseline and final nonperfusion was not significantly different between eyes that developed neovascularization and eyes that did not. Conclusion: In this population of severe central retinal vein occlusion eyes, profound retinal nonperfusion was observed with wide-field fluorescein angiography at baseline and the extent of nonperfusion progressed while undergoing anti-vascular endothelial growth factor therapy.

SAVE (Super-dose Anti-VEGF) Trial: 2.0 mg Ranibizumab for Recalcitrant Neovascular Age-Related Macular Degeneration: 1-Year Results

OBJECTIVES To assess durability of visual and anatomic gains with 2.0 mg ranibizumab in recalcitrant neovascular age-related macular degeneration (AMD). METHODS Phase I-II trial of 88 patients with recalcitrant neovascular AMD treated as needed every 4 (cohort A) or 6 weeks (cohort B) following three monthly doses. ETDRS refraction and spectral-domain OCT-guided as-needed re-treatments. RESULTS Seventy-nine patients completed the 12-month endpoint and were given 11.6 (cohort A) and 8.6 (cohort B) mean treatments. Mean best corrected visual acuity gains of 4.1 letters following three monthly doses were sustained for 12 months for both cohorts. Anatomic improvements were sustained for 12 months for cohort A, but not for cohort B; cohort B demonstrated a gradual increase in mean central retinal thickness (P = .03). CONCLUSION Visual and anatomic gains achieved with 2.0 mg ranibizumab in recalcitrant neovascular AMD were sustained for 1 year with monthly treatment. In comparison, anatomic gains were diminished with less than monthly treatment.

Long-term stability of circumferential silicone sponge scleral buckling exoplants

PURPOSE The historical extrusion/explantation rate of silicone sponge scleral buckle exoplants is 3.5 to 24.4%. This contrasts with the published 0.6 to 1.2% explantation rate of solid silicone elements. Previously reported silicone sponge exoplants studies were noncircumferential (quadrantic or multiple). This study was undertaken to assess the long-term stability of 360 degrees circumferentially placed 3 x 5 mm silicone sponge exoplants. METHODS Interventional case series of 840 consecutive circumferentially placed 3 x 5 mm silicone sponge exoplants. A retrospective review of operative reports and patient charts was performed. RESULTS A total of 552 patients had documented follow-up over 1 year. Median follow-up was 32.8 months. Six patients underwent removal of the scleral buckling element (two for diplopia, one acute postoperative infection, and three for extrusion). Median time to removal was 7.3 months. Extenuating circumstances contributed to two of the three extrusions. Of the entire series, fewer than 1% of patients required removal of the silicone sponge implant. Excluding patients with less than 1 year of documented follow-up, the long-term infection/extrusion rate was 0.7%. CONCLUSIONS Circumferentially placed silicone scleral buckling sponge elements are very stable and are well tolerated. The explantation/extrusion rate is comparable to published solid silicone element series.

Lucentis using Visudyne study: determining the threshold-dose fluence of verteporfin photodynamic therapy combined with intravitreal ranibizumab for exudative macular degeneration.

Purpose Combination verteporfin photodynamic therapy (vPDT) and antivascular endothelial growth factor (anti-VEGF) therapy may decrease the need for injections while maintaining visual acuity in exudative age-related macular degeneration. This pilot study was designed to determine the threshold fluence dose of vPDT (the dose required to demonstrate an effect on choroidal perfusion) combined with ranibizumab. Methods Seven patients were randomized to sham vPDT (two patients), 20% fluence vPDT (two patients), or 40% fluence vPDT (three patients) in combination with three-monthly intravitreal 0.5 mg ranibizumab injections. Intravitreal ranibizumab was reinjected if disease activity was seen on fluorescein angiography, optical coherence tomography, or clinical examination. Indocyanine green-determined choroidal hypoperfusion was graded in a masked fashion. Results Patients with 20% vPDT had mild hypoperfusion defects at seven days that resolved by week 4 (threshold dose); patients with 40% fluence vPDT had marked hypoperfusion at seven days that persisted as long as 12 months. Recruitment was stopped after limited efficacy was observed. One patient with 20% fluence vPDT lost 19 letters at one year; no other patient lost or gained >10 letters. Central retinal thickness decreased in six of seven patients, but ranibizumab injections did not decrease. Conclusion This pilot study shows that the threshold fluence dose of vPDT (when combined with ranibizumab) is approximately 20% standard fluence, and that mild and transient choroidal hypoperfusion can occur. Forty percent fluence vPDT causes a more prolonged and striking hypoperfusion. Despite hypoperfusion, no decrease in visual acuity or injections required was noted, suggesting that even higher fluence levels of vPDT may be necessary to decrease the number of anti-VEGF injections.

Use of nepafenac (Nevanac®) in combination with intravitreal anti-VEGF agents in the treatment of recalcitrant exudative macular degeneration requiring monthly injections

Purpose The purpose of this study is to determine the efficacy of combining topical nepafenac with monthly intravitreal injections of ranibizumab or bevacizumab in the treatment of recalcitrant exudative macular degeneration. Methods This was a retrospective, consecutive case series of patients with exudative macular degeneration requiring maintenance therapy of antivascular endothelial growth factor ( anti-VEGF) injections at least every 6 weeks, who were started on topical nepafenac. Despite frequent anti-VEGF dosing, all patients included in the study had persistence of any combination of the following: intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Patients underwent pinhole visual acuity, clinical exam, and optical coherence tomography (OCT) at baseline and every follow-up visit. Response to therapy was graded by reviewing quantitative and qualitative OCT data, and statistical analysis was done with paired Student’s t-test. Results Twenty-five patients (average age 77; 14 male and 11 female) were reviewed; the mean number of previous injections was 17.4 (range 3–31). Baseline mean visual acuity was 20/55, and final mean visual acuity after 3 months of treatment was 20/51 (P = 0.13). Monthly mean central foveal thickness measurements were 248, 250, 257, and 247 μm (P = 0.53) at baseline, 1, 2, and 3 months, respectively. By the end of the 3-month time point, qualitative OCT findings on 13 patients treated with nepafenac were classified as stable, 10 as better, and 2 as worse. Conclusions There was no significant change in visual acuity or quantitative OCT measurements, but there appeared to be a mild trend toward improved anatomy and qualitative OCT findings when topical nepafenac was added to monthly anti-VEGF injections in patients with persistent intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Further prospective studies with longer follow-up may be warranted.

Selected Clinical Comparisons of Spectral Domain and Time Domain Optical Coherence Tomography

The authors report four cases where spectral domain optical coherence tomography (SD-OCT) imaged pathology not captured by time domain optical coherence tomography (TD-OCT). These cases include one of angioid streaks, two of juxtafoveal telangiectasia, and one of age-related macular degeneration. In each case, the improved images provided by SD-OCT changed either the management of the patient or the counseling of their disease process.

THE ASSOCIATION OF EPIRETINAL MEMBRANE WITH MACULAR HOLE FORMATION AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR

Purpose: To describe the clinical and optical coherence tomography findings associated with the development of full-thickness macular holes after rhegmatogenous retinal detachment (RRD) repair. Methods: Retrospective, interventional case series. All patients who developed full-thickness macular holes after successful RRD repair from 3 clinical practices were reviewed. All cases of combined/simultaneous full-thickness macular hole and RRD were excluded. The main outcome measure was the presence of an epiretinal membrane at time of diagnosis of macular hole. Results: Twenty-five full-thickness macular holes were diagnosed after successful retinal detachment repair. Surgical approach to RRD repair included pneumatic retinopexy (6, 24%), scleral buckle alone (5, 20%), pars plana vitrectomy only (8, 32%), and combined scleral buckle and pars plana vitrectomy (6, 24%). The preceding RRD involved the macula in 19 patients (76%) before the formation of the macular hole. The median time to full-thickness macular hole diagnosis after RRD repair was 63 days (range, 4–4,080 days). An epiretinal membrane was present in all 25 (100%) macular holes. Two macular holes (8%) spontaneously closed, whereas the other 23 (92%) were successfully closed with a single surgical procedure. Mean visual acuity improved by approximately 5 lines to 20/72 (range, 20/20 to counting fingers at 1 foot) from 20/240 (range, 20/30 to hand motions) after macular hole repair (P < 0.0001). Conclusion: Full-thickness macular hole formation can occur after all types of RRD repair and is associated with an epiretinal membrane. The epiretinal membrane may play a role in the pathogenesis of secondary macular hole formation after RRD repair.