Gregg T. Kokame

Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration.

Purpose: To study retinal pigment epithelium (RPE) tears after off-label intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injection for neovascular age-related macular degeneration. Eyes with a vascularized pigment epithelial detachment (PED) that developed an RPE tear were compared with eyes with a vascularized PED but without an RPE tear. Methods: Nine retina specialists across the United States and in Europe participated in this retrospective case series. All eyes that received intravitreal bevacizumab injection for choroidal neovascularization (CNV) over 12 months (October 2005 to September 2006) were included. Eyes without all three confirmed tests (fluorescein angiography, fundus photography, and optical coherence tomography) were excluded from analysis. Statistical analyses were performed on multiple characteristics of eyes with a vascularized PED that did and did not develop an RPE tear. Results: Among 2,785 intravitreal bevacizumab injections for 1,064 eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15, 100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean subfoveal PED size was larger for eyes with tears than for those without tears (13.97 mm2 vs 9.9 mm2, respectively; P = 0.01; odds ratio, 1.09). There was substantially smaller mean ratio of CNV size to PED size for eyes with tears than for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean pre–bevacizumab injection best-corrected Snellen visual acuity was 20/162, and mean post–RPE tear best-corrected visual acuity was 20/160 (P = 0.48). Conclusion: Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED size (<50%) is more common in eyes with RPE tears. Vision may be preserved despite RPE tears.

Vision-threatening Complications of Surgery for Full-thickness Macular Holes

OBJECTIVE To study complications of vitrectomy surgery for full-thickness macular holes. DESIGN A multicentered, randomized, controlled clinical trial. PARTICIPANTS Community and university-based ophthalmology clinics. INTERVENTION Standardized macular hole surgery versus observation. MAIN OUTCOME MEASURES Assessment of anatomic and visual outcomes and determination of postoperative complications at 12 months after randomization. RESULTS Posterior segment complications were noted in 39 eyes (41%). The incidence of retinal pigment epithelium (RPE) alteration and retinal detachment (RD) were 33% and 11%, respectively. One RD due to a giant retinal tear resulted in a visual acuity of light perception. Other complications included a reopening of the macular hole in 2 eyes (2%), cystoid macular edema in 1 eye (1%), a choroidal neovascular membrane in 1 eye (1%) and endophthalmitis in 1 eye (1%). Eyes with complications had significantly worse visual acuity outcomes as determined by the Early Treatment Diabetic Retinopathy Study, Word Reading, and Potential Acuity Meter charts (P < 0.01 for all comparisons). Eyes with macular holes greater than 475 microns were more than twice as likely to have complications than eyes with holes less than 475 microns (odds ratio [OR] = 2.2, P = 0.07). Before surgery, the stage of the hole was related to postoperative RPE changes (P < 0.0001) and the occurrence of postoperative RD (P = 0.0002). Intraoperative trauma was related to the occurrence of these complications (P < 0.0001 for RPE changes, P = 0.02 for RDs). Epiretinal membrane removal was related to RPE changes (P = 0.02) but not RDs. CONCLUSIONS The RPE alterations and RDs are common after macular hole surgery and result in significantly reduced postoperative visual acuity. The RPE changes may be related to surgical trauma or light toxicity. Further efforts to reduce complications associated with macular hole surgery are indicated.

Vitrectomy for Prevention of Macular Holes: Results of a Randomized Multicenter Clinical Trial

PURPOSE: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. METHODS: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. RESULTS: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation (P = 0.81). This difference of 3% has a 95% confidence interval of (-21%, 27%). CONCLUSION: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.Purpose: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. Methods: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. Results: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation ( P = 0.81). This difference of 3% has a 95% confidence interval of (-21%,27%). Conclusion: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.

Optical coherence tomography-measured pigment epithelial detachment height as a predictor for retinal pigment epithelial tears associated with intravitreal bevacizumab injections.

Purpose: The purpose was to study preinjection optical coherence tomography–related factors in age-related macular degeneration eyes with retinal pigment epithelial detachment (PED) that may predispose retinal pigment epithelial (RPE) tears associated with intravitreal bevacizumab injections. Methods: This multicenter retrospective case series involving 9 retina specialists and 7 centers investigated Stratus optical coherence tomography (Carl Zeiss Meditec, Dublin, CA) parameters in eyes with vascularized PED (vPED) from February 2006 to February 2007. Of the 1,280 eyes in 1,255 patients receiving 2,890 intravitreal injections, there were 125 eyes with vPED. For every vPED eye that developed an RPE tear (Group 1), 3 or more vPED eyes without RPE tears (Group 2) were randomly selected in each study center during the same time period for comparison. The primary outcome measure was PED height (&mgr;m), and the secondary measures included volume index (vPED height × surface area), total macular volume, subretinal fluid, cystoid macular edema, center-point thickness, central 1 mm, and pre- and postinjection best-corrected Snellen visual acuities. Results: Twenty-one vPED eyes in 21 patients among 125 vPED eyes (16.8% of all vPED eyes) developed RPE tears. The 21 Group 1 eyes were compared with the 78 randomly selected Group 2 eyes. The vPED height was significantly higher for Group 1 eyes in comparison to Group 2 eyes (mean: 648.9 ± 245.0 vs. 338.1 ± 201.6 &mgr;m, P < 0.001). The same was true for the following: volume index (P = 0.001), subretinal fluid (P = 0.002), and total macular volume (P = 0.04). The mean preinjection and post-RPE tear best-corrected visual acuity were 0.92 logMAR (20/166) and 0.84 logMAR (20/137), respectively (P = 0.25). Multivariate analysis showed PED height to be the only significant risk factor associated with RPE tears in Group 1 eyes [odds ratio = 0.995 (95% confidence interval: 0.992–0.997), P < 0.001]. Conclusion: Elevated preinjection vPED height is the single most significant predictor for RPE tears after bevacizumab injections for vPED eyes. A vPED height >400 &mgr;m is associated with a significant risk for such a complication.

Paraproteinemias associated with serous detachments of the retinal pigment epithelium and neurosensory retina.

Background Serous retinal and retinal pigment epithelial detachments resembling central serous chorioretinopathy developed in three patients who had paraproteinemias. Methods The patients in this study were examined at two institutions, and their charts, photographs, and fluorescein angiograms were reviewed by the authors. Two patients had cryoglobulinemia and one had lgA, lgM benign gammopathy. Results These patients had decreased central visual acuity and metamorphopsia at the initial examination. All three patients were women. Two patients were taking systemic corticosteroids in tapering doses at the time of the initial examination. The multiple serous retinal pigment epithelial and retinal detachments were unilateral in one patient and bilateral in two patients. Two patients were treated with laser photocoagulation because of chronic visual loss and foveal detachments. At the most recent examination, each patient had visual acuity of 20/30 or better in both eyes and complete resolution of subretinal fluid. Conclusions Patients with paraproteinemia may develop multiple serous detachments of the retinal pigment epithelium and of the neurosensory retina. The chorioretinopathy in these patients may have been related to their paraproteinemia, type A personality, corticosteroid use, or a combination of these factors. The final visual acuity in these three patients was good.

Intraocular gas and low-altitude air flight.

Background: Air travel has been contraindicated for patients with intraocular gas on the basis of experimental studies, because of the risk of elevated intraocular pressure during atmospheric depressurization. Methods: A clinical study of gas bubble volume and intraocular pressure rise during a lowaltitude air flight was performed on a patient with a gas bubble volume of 65% after retinal detachment surgery. Results: The flight was well tolerated, and the patient did not experience pain or decreased vision. The maximum altitude of the flight was 3,000. Maximum intraocular pressure was 49 mmHg, with a baseline of 16 mmHg. Increases in intraocular pressure and bubble volume were instantaneous with changes in altitude. Implications for pressurized flight situations are discussed. Conclusion: Low-altitude air flight can be well tolerated by patients with intraocular gas, even with a relatively large vitreous cavity gas fill. Decisions about when to let patients with intraocular gas fly should be made on an case-to-case basis, depending on ocular factors and the planned flight characteristics.

Polypoidal Choroidal Vasculopathy Exudation and Hemorrhage: Results of Monthly Ranibizumab Therapy at One Year

Purpose: To evaluate the efficacy and safety of monthly intravitreal injections of ranibizumab in patients with polypoidal choroidal vasculopathy (PCV) and active exudation or hemorrhage. Methods: A prospective, single practice, open label trial of monthly intravitreal ranibizumab (0.5 mg) injections for PCV in 13 eyes of 13 patients who completed the 1-year study. The primary outcome measure was stabilization of vision (loss of <15 ETDRS letters). Secondary outcome measures included incidence of ocular and systemic adverse events, changes in subretinal hemorrhage, central foveal thickness, and polypoidal complexes on indocyanine green angiography at 1 year. Results: No patient lost ≥15 letters in visual acuity at 1 year. Three patients (23%) gained ≥15 letters at 12 months. Subretinal hemorrhage resolved in 9/9 eyes (100%). Macular edema improved in 5/5 eyes (100%). Subretinal fluid completely resolved in 4/9 eyes (44%), decreased in 2/9 eyes (22%), and increased in 3/9 eyes (33%). Polypoidal complexes decreased in 5/13 eyes (38%). Conclusion: Continuous monthly intravitreal ranibizumab decreases leakage and hemorrhage in eyes with exudative and hemorrhagic complications of PCV. Branching vascular networks persisted, and polypoidal complexes decreased in only 5/13 (38%) eyes with continuous antiangiogenic therapy at 1 year.

Early Stage of Macular Hole in a Severely Myopic Eye

PURPOSE/METHODS A progressive early stage of macular hole developed in a severely myopic eye of a 37-year-old woman. RESULTS/CONCLUSIONS The patient improved after pars plana vitrectomy, peeling of the posterior hyaloid, and gas-fluid exchange. Biomicroscopic, ultrasonographic, and intraoperative findings support the theory of cortical vitreous traction as the cause of macular hole in severely myopic eyes.

Subretinal surgery for peripapillary subretinal neovascular membranes.

Purpose: To report the results of surgical removal of extrafoveal peripapillary subretinal neovascular membranes (PSRNVMs) for elderly patients in whom visual acuity was threatened or affected by subretinal fluid, subretinal hemorrhage, subretinal exudate, or PSRNVM growth toward the fovea. Methods: Retrospective review of six eyes of six patients undergoing subretinal surgical removal of PSRNVMs via pars plana vitrectomy. Results: PSRNVMs were successfully removed in six eyes of six patients with initial preservation of foveal function. The preoperative Snellen visual acuity ranged from 20/40 to counting fingers, and the best postoperative visual acuity ranged from 20/25 to 20/40. The final visual acuity with a mean follow-up of 3 years (range, 6–63 months) was stable or improved in 83% (5 eyes) of cases, ranging from 20/25 to 20/80. Early recurrence of PSRNVM was noted only in 1 eye (17%) at 1 month after surgery and was successfully treated with laser photocoagulation. Late recurrence of choroidal neovascularization developed after 3 years in two eyes. Cataract developed in three of four phakic eyes. Conclusion: PSRNVMs sparing the central fovea in elderly patients can be successfully removed surgically with initial preservation of foveal function and with a low rate of early recurrence.

Short-term effectiveness of intravitreal bevacizumab versus ranibizumab injections for patients with neovascular age-related macular degeneration.

Purpose: To compare the effectiveness of three consecutive intravitreal injections of bevacizumab (Avastin) and ranibizumab (Lucentis) in patients with treatment-naïve neovascular age-related macular degeneration. Methods: This is a retrospective comparative study of qualifying consecutively treated patients (n = 176) with new-onset subfoveal choroidal neovascularization presenting at 6 retina referral centers. Patients were treated with 3 consecutive monthly injections of ranibizumab (0.5 mg) or 3 injections of bevacizumab every 6 weeks (1.25 mg) as determined by physician and patient preference. Ophthalmologic evaluations included monthly visual acuity measurements, ocular examinations, and optical coherence tomography imaging at each visit. Results: A 29.2% reduction in the mean central foveal thickness measurement through optical coherence tomography was found in the ranibizumab-treated patients versus a 20.9% reduction in the bevacizumab-treated patients (P ≤ 0.02). Fifty-three percent of ranibizumab-treated patients had returned to a central foveal thickness of <200 μm by the completion of 3 injections compared with 35% of patients treated with bevacizumab (P ≤ 0.07). No ocular or systemic adverse events were reported in either group. Conclusion: Short-term effectiveness of ranibizumab treatment, as measured by incremental improvement in optical coherence tomography parameters, was significantly greater than bevacizumab treatment, suggesting that there is a difference in the biologic activities of ranibizumab and bevacizumab.