Matthew S. Benz

Enzymatic Vitreolysis with Ocriplasmin for Vitreomacular Traction and Macular Holes

BACKGROUND Vitreomacular adhesion can lead to pathologic traction and macular hole. The standard treatment for severe, symptomatic vitreomacular adhesion is vitrectomy. Ocriplasmin is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface. METHODS We conducted two multicenter, randomized, double-blind, phase 3 clinical trials to compare a single intravitreal injection of ocriplasmin (125 μg) with a placebo injection in patients with symptomatic vitreomacular adhesion. The primary end point was resolution of vitreomacular adhesion at day 28. Secondary end points were total posterior vitreous detachment and nonsurgical closure of a macular hole at 28 days, avoidance of vitrectomy, and change in best-corrected visual acuity. RESULTS Overall, 652 eyes were treated: 464 with ocriplasmin and 188 with placebo. Vitreomacular adhesion resolved in 26.5% of ocriplasmin-injected eyes and in 10.1% of placebo-injected eyes (P<0.001). Total posterior vitreous detachment was more prevalent among the eyes treated with ocriplasmin than among those injected with placebo (13.4% vs. 3.7%, P<0.001). Nonsurgical closure of macular holes was achieved in 40.6% of ocriplasmin-injected eyes, as compared with 10.6% of placebo-injected eyes (P<0.001). The best-corrected visual acuity was more likely to improve by a gain of at least three lines on the eye chart with ocriplasmin than with placebo. Ocular adverse events (e.g., vitreous floaters, photopsia, or injection-related eye pain--all self-reported--or conjunctival hemorrhage) occurred in 68.4% of ocriplasmin-injected eyes and in 53.5% of placebo-injected eyes (P<0.001), and the incidence of serious ocular adverse events was similar in the two groups (P=0.26). CONCLUSIONS Intravitreal injection of the vitreolytic agent ocriplasmin resolved vitreomacular traction and closed macular holes in significantly more patients than did injection of placebo and was associated with a higher incidence of ocular adverse events, which were mainly transient. (Funded by ThromboGenics; ClinicalTrials.gov numbers, NCT00781859 and NCT00798317.).

Endophthalmitis isolates and antibiotic sensitivities: a 6-year review of culture-proven cases

PURPOSE To investigate the spectrum of organisms causing culture-proven endophthalmitis and their susceptibilities to commonly used antimicrobial agents over 10 years. DESIGN Retrospective, noncomparative, consecutive case series. METHODS Medical records were reviewed of all cases with culture-proven endophthalmitis at a single institution from 2002 through 2011. The outcome measures included all intravitreal isolates identified as well as antibiotic susceptibilities. RESULTS A total of 448 organisms were isolated during the study interval. The most common organisms identified were Staphylococcus epidermidis in 30.1% (135/448), Streptococcus viridians group in 10.9% (49/448), Staphylococcus aureus in 7.8% (35/448), Candida albicans in 5.8% (26/443), other coagulase-negative staphylococci in 6.0% (27/448), Propionibacterium acnes in 4.7% (21/448), and Pseudomonas aeruginosa in 3.1% (14/448). Overall, 327 (72.9%) of 448 isolates were gram-positive organisms, 48 (10.7%) of 448 isolates were gram-negative organisms, 71 (15.8%) of 448 isolates were fungi, and 2 (0.4%) of 448 isolates were viruses. For gram-positive organisms, susceptibilities were the following: vancomycin, 100%; gentamicin, 88.0%; sulfamethoxazole/trimethoprim, 77.5%; levofloxacin, 58.5%; oxacillin, 54.7%; ciprofloxacin, 51.0%; gatifloxacin, 51.0%; and moxifloxacin, 47.0%. For gram-negative organisms, susceptibilities were the following: ceftazidime, 100%; levofloxacin, 100%; ciprofloxacin, 95.0%; tobramycin, 90.6%; gentamicin, 80.6%; and sulfamethoxazole/trimethoprim, 59.4%. CONCLUSIONS In the current study, no single antibiotic provided coverage for all of the microbes isolated from eyes with endophthalmitis. Combination therapy generally is the recommendation as the initial empiric treatment of suspected bacterial endophthalmitis. Appropriate history and characteristic clinical features may guide the use of initial antifungal agents.

A Placebo-Controlled Trial of Microplasmin Intravitreous Injection to Facilitate Posterior Vitreous Detachment before Vitrectomy

PURPOSE To evaluate the safety and efficacy of a preoperative intravitreous injection of microplasmin in patients scheduled for vitreous surgery. DESIGN Phase 2, multicenter, placebo-controlled, double-masked, parallel-group, dose-ranging clinical trial. PARTICIPANTS One hundred twenty-five patients scheduled for pars plana vitrectomy (PPV), primarily for treatment of either vitreomacular traction or macular hole. INTERVENTION A single intravitreous injection of either microplasmin at 1 of 3 doses (25 microg, 75 microg, or 125 microg in 100 microl) or placebo injection administered 7 days before PPV. MAIN OUTCOME MEASURES Presence or absence of posterior vitreous detachment (PVD) at the time of PPV, progression of PVD, and resolution of vitreomacular interface abnormality precluding the need for PPV. RESULTS Rates of total PVD at the time of surgery were 10%, 14%, 18%, and 31% in the placebo group (n = 30), 25-microg (n = 29), 75-microg (n = 33), and 125-microg microplasmin groups (n = 32), respectively. The secondary end point resolution of vitreomacular interface abnormality precluding the need for vitrectomy at the 35-day time point was observed at rates of 3%, 10%, 15%, and 31% in the placebo, and the 25-microg, the 75-microg, and the 125-microg microplasmin groups, respectively. At the 180-day time point, the equivalent rates were 3%, 7%, 15%, and 28%, respectively. CONCLUSIONS Microplasmin injection at a dose of 125 microg led to a greater likelihood of induction and progression of PVD than placebo injection. Patients receiving microplasmin were significantly more likely not to require vitrectomy surgery. More definitive evaluation in phase 3 clinical trials therefore is warranted. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Efficacy of Intravitreal Ocriplasmin for Treatment of Vitreomacular Adhesion: Subgroup Analyses from Two Randomized Trials

PURPOSE To evaluate the efficacy of a single intravitreal injection of ocriplasmin 125 μg across relevant subpopulations of patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction (VMT), including when associated with macular hole. DESIGN Two multicenter, randomized, placebo-controlled, double-masked, 6-month studies. PARTICIPANTS A total of 652 randomized patients (464 receiving ocriplasmin; 188 receiving placebo). METHODS A single intravitreal injection of ocriplasmin 125 μg or placebo in the study eye. MAIN OUTCOME MEASURES Prespecified subgroup analyses were conducted to evaluate the effects on the proportion of patients with nonsurgical resolution of focal VMA at day 28, nonsurgical full-thickness macular hole (FTMH) closure at month 6, and categoric improvement in best-corrected visual acuity (BCVA) at month 6. RESULTS Resolution of VMA at day 28 was achieved more often in younger patients (<65 years), eyes without epiretinal membrane, eyes with FTMH, phakic eyes, and eyes with a focal VMA ≤ 1500 μm. Eyes with FTMH width ≤ 250 μm were more likely to achieve nonsurgical FTMH closure. Categoric ≥ 2-line and ≥ 3-line improvement in BCVA occurred more often in younger patients (<65 years) and in patients with a lower baseline BCVA (<65 letters). Treatment differences in favor of ocriplasmin were generally observed across each subgroup of subpopulations studied. CONCLUSIONS Subgroup analyses confirmed the positive effect of ocriplasmin across relevant subpopulations.

Primary Endpoint Results of a Phase II Study of Vascular Endothelial Growth Factor Trap-Eye in Wet Age-related Macular Degeneration

OBJECTIVE To evaluate the biologic effects and safety of vascular endothelial growth factor (VEGF) Trap-Eye during a 12-week fixed-dosing period in patients with neovascular (wet) age-related macular degeneration (AMD). DESIGN Multicenter, prospective, randomized, double-masked clinical trial with initial 12-week fixed dosing period. Data were analyzed to week 16. PARTICIPANTS We included 159 patients with subfoveal choroidal neovascularization secondary to wet AMD. METHODS Patients were randomized 1:1:1:1:1 to VEGF Trap-Eye during the fixed-dosing phase (day 1 to week 12): 0.5 or 2 mg every 4 weeks (0.5 mg q4wk, 2 mg q4wk) on day 1 and at weeks 4, 8, and 12; or 0.5, 2, or 4 mg every 12 weeks (0.5 mg q12wk, 2 mg q12wk, or 4 mg q12wk) on day 1 and at week 12. MAIN OUTCOME MEASURES The primary endpoint was change from baseline in central retinal/lesion thickness (CR/LT) at week 12; secondary outcomes included change in best-corrected visual acuity (BCVA), proportion of patients with a gain of ≥ 15 letters, proportion of patients with a loss of >15 letters, and safety. RESULTS At week 12, treatment with VEGF Trap-Eye resulted in a significant mean decrease in CR/LT of 119 μm from baseline in all groups combined (P<0.0001). The reduction in CR/LT with the 2 mg q4wk and 0.5mg q4wk regimens was significantly greater than each of the quarterly dosing regimens. The BCVA increased significantly by a mean of 5.7 letters at 12 weeks in the combined group (P<0.0001), with the greatest mean gain of >8 letters in the monthly dosing groups. At 8 weeks, BCVA improvements were similar with 2 mg q4wk and 2 mg q12wk dosing. After the last required dose at week 12, CR/LT and visual acuity were maintained or further improved at week 16 in all treatment groups. Ocular adverse events were mild and consistent with safety profiles reported for other intraocular anti-VEGF treatments. CONCLUSIONS Repeated monthly intravitreal dosing of VEGF Trap-Eye over 12 weeks demonstrated significant reductions in retinal thickness and improvements in visual acuity, and was well-tolerated in patients with neovascular AMD. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign).

Purpose While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. Methods Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. Results Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the “flying saucer” sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. Conclusion Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.

Anterior chamber and sutured posterior chamber intraocular lenses in eyes with poor capsular support.

Purpose: To compare the clinical outcomes and complications of patients who had surgical placement of anterior chamber (AC IOLs) and sutured posterior chamber intraocular lenses (PC IOLs) after cataract surgery resulting in poor capsular support. Setting: Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida. Methods: A retrospective interventional comparative case series of 181 eyes of 181 patients that had implantation of an intraocular lens with inadequate capsular support was conducted. A chart review of all patients that had implantation of AC IOLs or sutured PC IOLs at a tertiary care eye hospital between 1995 and 2001 was conducted. Results: Outcome measures included final best‐corrected visual acuity, spherical equivalent, and postoperative complications (pseudophakic bullous keratopathy, elevated intraocular pressure [IOP] inflammation, retinal detachment, suture erosion, cystoid macular edema). Of 702 charts reviewed, 181were found to fit inclusion and exclusion criteria. The postoperative complication risk ratio was 0.80 (95% confidence interval [CI]: 0.52–1.23) for AC IOLs compared with PC IOLs. The most common complication experienced by patients having implantation of either lens type was elevated IOP (AC IOL: 38%; PC IOL: 42%). The incidence of other complications was similar between the groups. Best‐corrected visual acuity was similar; however, final spherical equivalent trended toward more myopic values in the PC IOL group (−0.82 ± 1.67 for AC IOL versus −1.32 ± 2.12 for PC IOL). Conclusions: The findings suggest that no significant differences in outcome exist when comparing AC IOLs to sutured PC IOLs in complicated cataract extraction with poor capsular support. Recent advances in AC IOL design have yielded lenses that provide a safe, effective alternative to sutured PC IOLs.

Cystoid Macular Edema Secondary to Albumin-Bound Paclitaxel Therapy

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Progressive outer retinal necrosis in immunocompetent patients treated initially for optic neuropathy with systemic corticosteroids

PURPOSE To report two cases of progressive outer retinal necrosis occurring in immunocompetent individuals after treatment with corticosteroids for presumed optic neuropathy. DESIGN Observational case report. SETTING University-based tertiary eye hospital. METHODS Retrospective review of existing clinical records. RESULTS Two patients were treated empirically with systemic corticosteroids for suspected inflammatory papillopathy. Subsequently, both were diagnosed with necrotizing herpetic retinitis with features of progressive outer retinal necrosis. Anterior chamber paracentesis confirmed varicella-zoster infection. Both patients were human immunodeficiency virus negative; one patient with rheumatoid arthritis was taking etanercept. Both became completely blind in one eye despite intensive treatment with antiviral medication intravenously and intravitreally. CONCLUSIONS Progressive outer retinal necrosis is not confined to patients with underlying severe immunodeficiency, such as acquired immune deficiency syndrome. Initial treatment of acute, unexplained vision loss with systemic corticosteroids may lead to catastrophic visual loss in patients with evolving necrotizing herpetic retinopathy.

Optical coherence tomography of idiopathic juxtafoveolar telangiectasia.

BACKGROUND AND OBJECTIVE To document optical coherence tomography (OCT) findings in a series of eyes with group 2A idiopathic juxtafoveal telangiectasia. PATIENTS AND METHODS This study is a retrospective review of patient charts, OCT, fundus photography, and fluorescein angiography involving 23 eyes (12 patients). Mean retinal thickness in 9 macular areas was calculated and compared to previously published measurements from normal eyes. RESULTS OCT in 8 of 13 stage 3 eyes revealed foveal cysts without evidence of cystoid macular edema on fluorescein angiography or biomicroscopy, and 1 lamellar hole. In stage 3 eyes, mild retinal thickening was found in 7 of 9 macular areas (P < .05). CONCLUSIONS OCT commonly reveals foveal cysts in stage 3 idiopathic juxtafoveal telangiectasia. Consistent findings of associated mild macular thickening and lack of late petaloid hyperfluorescence on fluorescein angiography suggest that these cysts differ in pathophysiology from cystoid macular