Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial.

PURPOSE: To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate age-related macular degeneration (AMD) for patients with preexisting nAMD in their contralateral eye. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Adults aged 50 years and older with intermediate AMD (multiple intermediate drusen [≥63 µm and <125 µm] or ≥1 large drusen [≥125 µm] and pigmentary changes) in the study eye and nAMD in the contralateral eye. INTERVENTION: Intravitreal ranibizumab injection (0.5 mg) or sham injection every 3 months for 24 months. MAIN OUTCOME MEASURES: Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary). RESULTS: Among 108 enrolled participants (54 [50%] in each group), all except 2 were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). Conversion to nAMD over 24 months occurred among 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio = 0.91 [95% confidence interval (CI), 0.32-2.59]; P = 0.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was -2.1 letters (standard deviation, 5.4 letters) with ranibizumab and -1.4 letters (standard deviation, 7.7 letters) with sham (adjusted difference = -0.8 letters [95% CI, -3.7 to 2.2 letters]; P = 0.62). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group. CONCLUSIONS: Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed.

Meticulous multimodal analysis of aflibercept therapy for submacular vascularized pigment epithelial detachment associated with neovascular AMD in a prospective case series, the EVEN study.

PURPOSE: This prospective case series investigates the visual and anatomical outcomes including detailed volumetrics of eyes with vascularized pigment epithelial detachments (PED) treated with aflibercept in eyes with neovascular age-related macular degeneration (nAMD) through meticulous analysis in a reading center setting. METHODS: We conducted a single-arm multicenter, prospective, open-labeled, interventional case series, comparing visual and anatomic outcomes at 12 months with baseline for intense aflibercept therapy. Eyes with submacular vascularized PED due to AMD received 2.0 mG of intravitreal aflibercept at baseline and then monthly for 6 months. During the subsequent 6 months, mandatory aflibercept therapy was given for every other month, while additional aflibercept injections were allowed between mandatory injections if necessary, at 4 weeks after last injection, contingent on pre-defined visual and anatomic re-treatment criteria. Standardized ETDRS vision measurement, anterior and posterior segment examination, and high-density spectral-domain optical coherence tomography scans were obtained at baseline and monthly, while fundus photography and fluorescein angiography were obtained at baseline, 3,6, and 12 months. Indocyanine-green angiography was obtained at baseline and 3 months. Meticulous multidimensional assessment of the scanned multimodal serial images was then performed by Doheny Image Reading Center. RESULTS: Of 36 eyes and patients with mean age of 80, mean baseline and 12-month-ETDRS BCVA was 59 ± 8.9 letters (20/66), and 65 ± 27 letters (20/50), respectively; (6.5 letters improvement, p = 0.02). Significant reductions from baseline to month-12 were noted for multiple anatomic measures, including PED maximum height, entire lesion and central 1-mm subfield of PED mean thickness and volume, and mean subretinal hyperreflective material (SHRM) thickness and volume, also entire lesion of retinal thickness, retinal volume, and mean subretinal fluid (SRF) thickness (mean reductions in magnitude ranging from 37.5 to 91.7%, all p < 0.001). FA measurements also showed significant decrease from baseline to month-12, including area and greatest linear diameter (GLD) of fibrovascular PED, area and GLD of NV area and leakage (mean reductions in magnitude from 41.9 to 87.7%, p value from 0.002 to <0.001). This case series shows that while majority of reductions in SRF volume occurred during first month from baseline, majority of reduction in retinal, PED, and SHRM volumes occurred during first 2 months after onset of anti-VEGF injections. RPE tears developed in 5 eyes (13.9%) correlating with eyes with large PED height and volume at baseline (mean height >800 µm, mean volume >4 mm3). Geographic atrophy (GA) was noted in only 1 eye at baseline, but in 16 eyes (44.4%) by 12 months. CONCLUSIONS AND IMPORTANCE: Significant improvement in vision and anatomic measures including volumetrics of vPED were noted at 12 months after aflibercept therapy. Besides substantial PED height, large PED volume at baseline also correlated with RPE tears in 13.9% of eyes with vPED after anti-VEGF therapy. Reduction in SHRM correlated directly with decrease in PED, and more than 40% of study eyes developed GA by 12 months following intense anti-VEGF therapy.

TYPE 1 VERSUS TYPE 3 NEOVASCULARIZATION IN PIGMENT EPITHELIAL DETACHMENTS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Prospective Study.

PURPOSE: To evaluate the response to aflibercept therapy for Type 1 and Type 3 neovascularization in pigment epithelial detachments associated with treatment-naive, neovascular age-related macular degeneration. METHODS: In this multicentered, prospective study, eligible eyes underwent an intravitreal aflibercept injection protocol for 12 months. Visual acuity and morphologic features of the pigment epithelial detachments were compared at baseline and follow-up intervals between eyes with Type 1 versus Type 3 neovascularization. RESULTS: Thirty-six eyes were analyzed. At 12 months, Type 1 lesions showed a 4.5 ± 23 Early Treatment of Diabetic Retinopathy Study letter improvement (P = 0.1665) versus a 14 ± 11 (P = 0.0072) letter improvement with Type 3 lesions. Both Type 1 and 3 eyes showed a significant decrease in pigment epithelial detachment size, subretinal fluid, and subretinal hyperreflective material; however, Type 3 eyes had a greater reduction in pigment epithelial detachment size and subretinal hyperreflective material, as well as a reduction in central retinal thickness. Type 1 eyes required an average of 1.636 (range, 1-4) injections to resolve fluid, which was greater than Type 3 eyes, which required an average of 1.143 (range, 1-2) injections (P = 0.0251). CONCLUSION: Intravitreal aflibercept injections were efficacious for pigment epithelial detachments, but baseline and follow-up anatomical and functional outcomes differed in Type 1 versus Type 3 neovascularization. The better response of Type 3 eyes with fewer injections suggests that differentiation of the neovascularization subtype at the initial diagnosis may allow for a more tailored, optimal therapy.

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 (microm), and the secondary measures included volume index (vPED height x 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 microm, 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 microm is associated with a significant risk for such a complication.

Pneumatic retinopexy for the repair of retinal detachments: a comprehensive review (1986-2007).

Pneumatic retinopexy has become an important surgical technique in the modern era of retinal surgical management for retinal detachments. It is primarily indicated for uncomplicated retinal detachments with retinal breaks involving the superior 8 clock hours of the fundus, although more complex retinal detachments may be successfully managed with this technique on a selected basis. Qualified candidates must be willing to maintain a specific head posture for five or more days for optimal outcome with pneumatic retinopexy. Basic surgical steps of pneumatic retinopexy include retinopexy of retinal breaks with cryotherapy or laser, intraocular gas injection before or after retinopexy, and maintenance of proper head posture by the patient for the required time period after surgery. Phakic eyes fared better than nonphakic eyes for pneumatic retinopexy, with the single-operation successes of 71-84% for the former and 41-67% for the latter. Despite lower single-operation successes with pneumatic retinopexy in comparison to sclera buckling, the multicenter pneumatic retinopexy trial and other published reports have shown that the final anatomical and visual outcomes are not disadvantaged by the initial pneumatic retinopexy. An extensive discussion of complications associated with pneumatic retinopexy is presented. In addition, a key feature of this review is a comprehensive update in the outcome of pneumatic retinopexy in published reports from 1986 to the present in chronological order not available in the current literature. This comprehensive summary shows updated average surgical outcomes for the 4,138 eyes in the 21-year period to be similar to previous reports: single-operation successes (74.4%), final operation successes (96.1%), new retinal breaks (11.7%), and proliferative vitreoretinopathy (5.2%).

Modified haptic externalizing technique for repositioning dislocated 1-piece acrylic posterior chamber implants.

BACKGROUND: To describe a novel vitreoretinal technique and the results of repositioning dislocated 1-piece acrylic posterior chamber intraocular lenses (PCIOL). METHODS: This retrospective study included 7 eyes of 7 patients (ages 41 to 82) who underwent repositioning surgery with vitreoretinal methodology for dislocated 1-piece acrylic PCIOL between 2003 and 2005. Repositioning surgery involved temporary haptic externalization via anterior sclerotomies and passing curved needles of 9-0 or 10-0 polypropylene sutures through soft distal knobs of haptics before reinternalization for sulcus fixation. RESULTS: All 7 repositioned PCIOL remained centered and stable after 12 to 28 months of follow-up (mean = 17.6 months). Mild anterior-posterior intraocular lens (IOL)-tilting developed in 1 eye, but the IOL remained centered and secured in the sulcus with good vision. One PCIOL was exchanged with an anterior chamber intraocular lens (ACIOL) 1 year after repositioning because of recurrent intraocular hemorrhage and cystoid macular edema. Preoperative best corrected Snellen visual acuity (BCVA) ranged from 20/40 to 5/200 (median = 20/70). Postoperative BCVA ranged from 20/20 to 20/200 (median = 20/40). Capsular defect was the cause of IOL dislocation for all cases. Four of 7 eyes (57.1%) had axial myopia. INTERPRETATION: This repositioning technique for dislocated all-acrylic PCIOL prevents suture slippage and allows secured sulcus fixation. Repositioned haptics should be sutured more than 1 mm from the limbus to avoid iris chafing.

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 mm vs 9.9 mm, 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.

Ocular features of west nile virus infection in North America: a study of 14 eyes.

PURPOSE: To present a case series of ocular findings of West Nile virus infection (WNVI) in North America. DESIGN: Retrospective, noncomparative, observational case series. PARTICIPANTS: All patients were referred to the authors for WNVI with ocular involvement between the years 2002 and 2005. METHODS: Chart review was performed on all participants. All participants underwent complete ophthalmic evaluation during each examination, including best-corrected Snellen visual acuity measurement, tonometry, slit-lamp biomicroscopy of the anterior and posterior segments, and dilated fundus examination with indirect ophthalmoscopy. Fundus photography and fluorescein angiography were also performed on all eyes. Relevant ocular findings associated with WNVI were recorded and tabulated. MAIN OUTCOME MEASURES: The authors studied the characteristics, frequency, and locations of ocular lesions found in participants' eyes. RESULTS: There were 14 eyes (7 patients) with ocular West Nile virus lesions from 2002 to 2005. Average patient age was 58.4 years (range, 32-85 years). Ocular findings in descending order of frequency included multifocal chorioretinal target lesions in 12 eyes (85.7%), retinal hemorrhages in 7 eyes (50.0%), vitritis in 6 eyes (42.9%), chorioretinal linear streaks in 4 eyes (28.6%), perivascular sheathing and vasculitis in 4 eyes (28.6%), narrowed retinal vessels in 4 eyes (28.6%), disc edema in 4 eyes (28.6%), optic atrophy in 2 eyes (14.3%), vascular occlusion in 2 eyes (14.3%), and VIth nerve palsy in 1 eye (7.1%). Peripheral fundus lesions were found in all 14 eyes (100%), whereas posterior fundus lesions were found in 8 eyes (57.1%). Five patients (71.4%) were diabetic. Diabetic retinopathy was present in 7 eyes (70%). CONCLUSIONS: Multifocal choroiditis is the most common ocular manifestation associated with WNVI, with a typically benign clinical course. Less frequent ocular lesions, including optic neuritis and occlusive vasculitis, frequently induce persistent and likely permanent visual deficit. Diabetic patients and those older than 50 years of age are more vulnerable to the more severe features of WNVI, including more serious ocular lesions.

Characteristics of sixty myopic eyes with pre-laser in situ keratomileusis retinal examination and post-laser in situ keratomileusis retinal lesions.

PURPOSE: A survey of eyes with pre-laser in situ keratomileusis (LASIK) retinal examinations and characteristics of post-LASIK retinal breaks and retinal detachments (RDs). METHODS: A survey of worldwide vitreoretinal surgeons (424 physicians). Surveyed information included demographics, best-corrected visual acuity, degree of myopia, pre- and post-LASIK retinal findings, follow-up time, and treatment outcome. RESULTS: Sixty eyes with pre-LASIK retinal examinations developed post-LASIK retinal breaks and RDs. There was an average of 2.3 breaks per eye, yielding a total of 140 breaks in the 60 eyes. Forty eyes also had RDs besides the retinal breaks. Large percentages of eyes had substantial myopia (mean myopia, -9.5 +/- 5.8 diopters [D]) and complex vitreoretinal complications. Forty percent developed vitreoretinal complications within 6 months after LASIK. The 20 eyes that developed more extensive RDs (>3 clock hours) had a significantly higher mean myopia than did the 6 eyes that developed limited RD (< or = 3 clock hours) within 12 months after LASIK (-8.92 +/- 6.82 D versus -3.50 +/- 1.97 D, P = 0.03). There were significant statistical differences in distribution of retinal breaks and tears between the temporal and nasal quadrants (P < 0.001, P < 0.001, respectively, chi2, but not between the superior and inferior quadrants. CONCLUSION: Distributions of retinal breaks in this study were comparable with results found in non-LASIK eyes in young myopes. Treatment for post-LASIK vitreoretinal complications was highly successful. The vulnerability of such highly myopic eyes for vitreoretinal complications warrants their close monitoring.

Acute exudative polymorphous vitelliform maculopathy syndrome.

PURPOSE: The authors describe clinical characteristics of acute exudative polymorphous vitelliform maculopathy syndrome, also termed polymorphous maculopathy syndrome (PMS), an unusual tapetoretinal disorder first reported by Gass. METHODS: Detailed ophthalmoscopy, fluorescein angiography, electrophysiology, and optical coherence tomography (OCT) were performed on a patient with PMS. RESULTS: Numerous small, yellowish lesions arranged in a honeycombed pattern at the level of the retinal pigment epithelium (RPE) around the disk and the macula, a shallow macular detachment (documented by OCT), and a perifoveolar yellow ring appeared in both eyes. Initial fluorescein angiography revealed mild early hyperfluorescence and late staining of the perifoveolar rings and the multifocal yellow lesions. Gradually, subretinal yellowish deposits gravitated as a meniscus below the macula with subsequent further changes. Electrophysiology showed reduced amplitudes of the electroretinogram and electrooculogram and abnormal dark adaptometry. A rhegmatogenous retinal detachment in the left eye was successfully repaired, with a visual acuity of 20/30. Antecedent upper respiratory infection and headaches and positive serology for the coxsackie virus suggest the possibility of a virus-induced disorder. Genetic studies of this patient showed normal DNA sequences for the bestrophin and peripherin/RDS genes. CONCLUSION: This is the first report of PMS with the following characteristics: occurrence in a woman, development of a rhegmatogenous retinal detachment, and electroretinogram, visual-evoked response, color vision, and OCT findings. PMS has features similar to but also different from those of Harada disease and Best disease. Further studies are necessary to determine its relationship to other acquired conditions, such as virus-induced disorders, and genetic defects unrelated to abnormalities of the bestrophin and peripherin/RDS genes.