Ingrid U. Scott

Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema

OBJECTIVE Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). DESIGN Multicenter, randomized clinical trial. PARTICIPANTS A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. METHODS Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (> or =24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. MAIN OUTCOME MEASURES Best-corrected visual acuity and safety at 1 year. RESULTS The 1-year mean change (+/-standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9+/-11, P<0.001) and ranibizumab + deferred laser group (+9+/-12, P<0.001) but not in the triamcinolone + prompt laser group (+4+/-13, P=0.31) compared with the sham + prompt laser group (+3+/-13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. CONCLUSIONS Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation.

A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion: The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study Report 5

OBJECTIVE To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). METHODS Multicenter, randomized, clinical trial of 271 participants. MAIN OUTCOME MEASURE Gain in visual acuity letter score of 15 or more from baseline to month 12. RESULTS Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.8-14.1; P = .001) and 5.0 times greater in 4-mg group than the observation group (OR, 5.0; 95% CI, 1.8-14.4; P = .001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P = .97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group. CONCLUSIONS Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial. Trial Registration clinicaltrials.gov Identifier: NCT00105027.

Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.

OBJECTIVE To report expanded 2-year follow-up of a previously reported randomized trial evaluating intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). DESIGN Multicenter, randomized clinical trial. PARTICIPANTS A total of 854 study eyes of 691 participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. METHODS Continuation of procedures previously reported for the randomized trial. MAIN OUTCOME MEASURES Best-corrected visual acuity and safety at the 2-year visit. RESULTS At the 2-year visit, compared with the sham + prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI], -0.4 to +7.7), 5.8 letters greater in the ranibizumab + deferred laser group (95% aCI, +1.9 to +9.8), and 1.5 letters worse in the triamcinolone + prompt laser group (95% aCI, -5.5 to +2.4). After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness ≥250 μm were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. CONCLUSIONS The expanded 2-year results reported are similar to results published previously and reinforce the conclusions originally reported: Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial, including vision impairment with DME involving the center of the macula.

Evolving guidelines for intravitreous injections.

Intravitreous (IVT) injection is increasingly being incorporated into the management of ocular diseases. While only fomivirsen sodium (Vitravene™) is currently approved by the Food and Drug Administration as an IVT injection, the number of approved IVT injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for IVT injection. The purpose of this document is to identify specific strategies for the delivery of IVT injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of IVT injection, additional clinical experience, and results of clinical trials.

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.

Expert Agreement in Evaluating the Optic Disc for Glaucoma

The authors studied intraobserver and interobserver agreement, under monoscopic and stereoscopic conditions, in estimating vertical cup-to-disc ratios and in assessing whether a disc had glaucomatous damage. Six glaucoma experts evaluated 75 optic disc photographs under both viewing conditions. The experts also re-evaluated 25 photographs. Intraobserver agreement in estimating vertical cup-to disc ratios was high (median weighted kappa, 0.79). Interobserver agreement in estimating vertical cup-to-disc ratios was moderate (stereoscopic median weighted kappa, 0.67); individual experts differed by as much as 0.2 disc diameters (DD) monoscopically and 0.16 DD stereoscopically. The observers estimated larger vertical cup-to-disc ratios when evaluating the same discs under stereoscopic conditions than under monoscopic conditions. Intraobserver agreement in assessing glaucomatous disc damage was substantial (median kappa, 0.76). Interobserver agreement in assessing glaucomatous damage was moderate (stereoscopic median kappa, 0.50). This study confirms the ability of experts to reliably evaluate the optic disc within themselves and emphasizes the need for developing standardized methods for interobserver evaluation of the optic disc in glaucoma.

Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study).

Objective: To evaluate the short-term fluorescein angiographic and visual acuity effects of a single intravitreal injection of bevacizumab (Avastin) for the management of persistent new vessels (NV) associated with diabetic retinopathy. Methods: A prospective, nonrandomized open-label study of diabetic patients with actively leaking NV refractory to laser treatment and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA) worse than 20/40. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 (±1) following intravitreal injection of 1.5 mg of bevacizumab. Main outcome measures include changes in total area of fluorescein leakage from active NV and BCVA. Results: Fifteen consecutive patients (men, 9 [60%]; women, 6 [40%]) were included and all completed the 12-week follow-up period of the study. The mean ± SD age of participants was 60.08 ± 7.75 years (median, 59.5; range, 49–73 years). At baseline, mean ± standard error of the mean (SEM) NV leakage area was 27.79 ± 6.29 mm2. The mean ± SEM area of active leaking NV decreased significantly to 5.43 ± 2.18 mm2 and 5.50 ± 1.24 mm2 (P < 0.05, Tukey multiple comparisons post-test) at 1 and 12 weeks postinjection, respectively; at week 6 no leakage was observed. The mean ± SEM logMAR (Snellen equivalent) BCVA improved significantly from 0.90 (20/160) ± 0.11 at baseline to 0.76 (20/125+2) ± 0.12, 0.77 (20/125+2) ± 0.11, and 0.77 (20/125+2) ± 0.12 at weeks 1, 6, and 12, respectively (P < 0.05, Tukey multiple comparisons post-test). No major adverse events were observed. Conclusions: Intravitreal injection of bevacizumab achieved short-term reduction of fluorescein leakage from persistent active NV without loss of vision in patients with diabetic retinopathy. Further studies to investigate the role of anti-VEGF therapy with bevacizumab for the management of diabetic retinopathy refractory to laser treatment are warranted.

Endophthalmitis After 25-gauge And 20-gauge Pars Plana Vitrectomy: Incidence and Outcomes

Purpose: To compare the rates of endophthalmitis after 20-gauge versus 25-gauge pars plana vitrectomy (PPV) and to investigate clinical features of, and visual acuity outcomes, for patients with endophthalmitis after PPV. Methods: A computerized database search was performed at each author’s institution to identify all patients who underwent PPV by any of the authors between January 1, 2005, and December 31, 2006, and were subsequently treated for endophthalmitis. In addition, all patients who underwent PPV and were subsequently treated for endophthalmitis at Pennsylvania State College of Medicine (Hershey, PA) and Bascom Palmer Eye Institute (Miami, FL) during the study period were included. The medical records of these patients were reviewed to confirm that the endophthalmitis was associated with PPV and to collect clinical data to meet the study objectives. Results: The incidence of endophthalmitis during the study period was 2 cases per 6,375 patients (or 1 case per 3,188 patients; 0.03%) for 20-gauge PPV compared with 11 cases per 1,307 patients (or 1 case per 119 patients; 0.84%) for 25-gauge PPV (P < 0.0001). Of 11 eyes that developed endophthalmitis after 25-gauge PPV, 9 received endophthalmitis prophylaxis with subconjunctival cefazolin after surgery. Median intraocular pressure on postoperative day 1 was 13 mmHg (range, 5–27 mmHg). Median time between PPV and endophthalmitis presentation was 3 days (range, 1–15 days). Presenting vision was hand motions or better in all eyes. Initial treatment included vitreous tap and injection of antibiotics in nine eyes and PPV and injection of antibiotics in two. All patients received intraocular treatment with vancomycin, and 10 received ceftazidime treatment. Eight patients had final visual acuity of ≥20/400, and four had visual acuity of ≥20/63. Cultures were negative in three cases; no culture specimens were obtained in one case. Six of the seven isolates were coagulase-negative staphylococci, and one was enterococcus. Five of six isolates tested for sensitivity to vancomycin were sensitive, and both isolates tested for sensitivity to ceftazidime were sensitive. Conclusions: The rate of endophthalmitis after 25-gauge PPV was significantly higher than that after 20-gauge PPV. Endophthalmitis after 25-gauge PPV occurred within 15 days of PPV, was usually due to coagulase-negative staphylococci sensitive to vancomycin, and was associated with variable visual outcomes.

Silicone oil in the repair of complex retinal detachments. A prospective observational multicenter study.

OBJECTIVE This study aimed to report anatomic and visual acuity outcomes and complications after 1000-centistoke silicone oil was used as a retinal tamponade for the treatment of complex retinal detachments. DESIGN Prospective observational multicenter study conducted at community and university-based ophthalmology clinics. PARTICIPANTS The study cohort consisted of 2439 patients (2573 eyes) treated for complex retinal detachments associated with cytomegalovirus (CMV) necrotizing retinitis or a non-CMV etiology, including proliferative diabetic retinopathy, giant retinal tears, proliferative vitreoretinopathy, or ocular trauma. INTERVENTION Vitrectomy surgery was performed for complex retinal detachment with 1000-centistoke silicone oil as the retinal tamponade. MAIN OUTCOME MEASURES Anatomic outcomes were complete retinal attachment and macular attachment. Visual acuity outcomes were ambulatory vision (> or = 4/200) and preservation of preoperative visual acuity. Complications were rates of secondary intraocular pressure elevation (> or = 30 mmHg), hypotony (< or = 5 mmHg), corneal opacification (including band keratopathy, corneal edema, and corneal abrasions), oil emulsification, and cataract. Outcomes were assessed 6, 12, and 24 months after surgery. RESULTS At the 6-month examination, the retina was completely attached in 178 (78%) of 228 CMV eyes and in 855 (70%) of 1219 non-CMV eyes. The macula was attached in 216 (95%) of 228 and 1062 (89%) of 1189 CMV and non-CMV eyes, respectively. Ambulatory vision was noted in 151 (65%) of 234 CMV eyes and in 480 (38%) of 1251 non-CMV eyes. Visual acuity was preserved in 106 (46%) of 230 and 1035 (84%) of 1229 CMV and non-CMV eyes, respectively. The corresponding rates of complications for CMV and non-CMV eyes were: elevated intraocular pressure, 0 (0%) of 196 and 35 (3%) of 1196; hypotony, 11 (6%) of 196 and 228 (19%) of 1196; corneal opacity, 13 (6%) of 229 and 326 (26%) of 1248; emulsification, 3 (1%) of 211 and 29 (3%) of 959; and cataract in phakic eyes, 118 (64%) of 185 and 50 (63%) of 80. CONCLUSIONS Retinal reattachment was achieved in the majority of eyes using vitrectomy and silicone oil retinal tamponade. Complication rates generally were less frequent in CMV eyes, but follow-up was shorter in this group of patients, largely because of reduced life expectancy. Cataract frequently developed in phakic eyes of study patients. Use of 1000-centistoke silicone oil can be considered in the management of complex retinal detachments associated with multiple etiologies.

FACTORS ASSOCIATED WITH REDUCED VISUAL ACUITY DURING LONG-TERM FOLLOW-UP OF PATIENTS WITH IDIOPATHIC CENTRAL SEROUS CHORIORETINOPATHY

Purpose To investigate factors associated with reduced visual acuity during long-term follow-up of patients with idiopathic central serous chorioretinopathy (ICSC). Methods Retrospective consecutive case series that included patients with ICSC who were younger than 50 years of age at the time of initial examination and were followed up for ≥3 years. Results The mean follow-up for 101 involved eyes of 61 patients was 9.8 years (median, 8.0 years). Eyes were stratified into two groups based on visual acuity at the final examination: Group 1, visual acuity of 20/40 or better; and Group 2, visual acuity of worse than 20/40. Findings identified as potential risk factors for reduced vision at the final follow-up examinations for Group 1 versus Group 2 included the following: macular retinal pigment epithelium atrophy (90.8% versus 96.0%, respectively;P = 0.68); persistent pigment epithelial detachment or persistent subretinal fluid (5.3% versus 28.0%, respectively;P = 0.004); recurrences (39.5% versus 68.0%, respectively;P = 0.020); laser treatment (28.9% versus 32.0%, respectively;P = 0.80); and submacular choroidal neovascularization (0.0 versus 8.0%, respectively;P = 0.059). Conclusions Factors associated with reduced visual acuity during long-term follow-up of patients with ICSC included persistent pigment epithelial detachment and/or subretinal fluid, recurrences, and submacular choroidal neovascularization.