John S. Pollack

Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.

OBJECTIVES To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME). DESIGN Prospective, randomized, interventional, multicenter clinical trial. PARTICIPANTS One hundred twenty-six patients with DME. METHODS Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ. MAIN OUTCOME MEASURES The mean change from baseline in best-corrected visual acuity (BCVA) at month 24. RESULTS After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 μm or less was 36%, 47%, and 68%, respectively. CONCLUSIONS Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Incidence of endophthalmitis related to intravitreal injection of bevacizumab and ranibizumab.

Purpose: To report the overall incidence of endophthalmitis associated with office based intravitreal injections of bevacizumab and ranibizumab. Methods: This is a retrospective, consecutive, multicenter case series involving four large clinical sites. Included were all patients receiving at least one injection of intravitreal bevacizumab or intravitreal ranibizumab. Follow-up after each injection was at least 4 weeks. Results: A total of 12,585 injections of intravitreal bevacizumab and 14,320 injections of intravitreal ranibizumab were given during the study period. Infectious endophthalmitis developed in three patients after administration of bevacizumab and in three patients after administration of ranibizumab. Four of these patients were culture positive. Rates of endophthalmitis were 0.02% and 0.02%, respectively, with an overall rate of 0.02%. Conclusion: The rate of endophthalmitis associated with intravitreal bevacizumab and ranibizumab is low, with an incidence of approximately 1 in 4,500 injections.

Short-term Outcomes of 23-gauge Pars Plana Vitrectomy

PURPOSE To report the initial experience and safety profile of 23-gauge pars plana vitrectomy (PPV) in eyes undergoing vitreoretinal surgery. DESIGN Retrospective, multicenter, consecutive, interventional case series. METHODS The inclusion criteria for this study included eyes that underwent primary, 23-gauge PPV for various indications including, but not limited to, epiretinal membrane, nonclearing vitreous hemorrhage, idiopathic macular hole, and rhegmatogenous retinal detachment (RD), and postoperative follow-up of at least 12 weeks. Exclusion criteria included history of prior vitrectomy, glaucoma filtration surgery, or administration of gas at expansile concentrations. Main outcome measures included best-corrected Snellen visual acuity (VA), intraocular pressure (IOP), intraoperative complications, and postoperative complications. RESULTS Ninety-two patients met the inclusion criteria. The overall VA improved from 20/238 (range, 20/25 to hand motions [HM]) preoperatively to 20/82 (range, 20/20 to HM) postoperatively (P < .001). Each surgical indication experienced a statistically significant VA improvement. Intraoperative complications included retinal tears observed in two eyes (2.2%). Sclerotomy sutures were required intraoperatively in two eyes (2.2%). Postoperative complications included postoperative day 1 hypotony in six eyes (6.5%), a retinal tear in one eye (1.1%), and a recurrent RD in one eye (1.1%). No cases of endophthalmitis were observed. CONCLUSIONS Intraoperative and postoperative complications were rare in this series of 23-gauge vitrectomy. Postoperative day 1 hypotony was the most common complication observed. All cases of postoperative hypotony resolved at postoperative week 1 without intervention. Retinal tear or detachment was an uncommon complication in the intraoperative and postoperative settings. Postoperative endophthalmitis was not noted in this case series.

Postoperative abnormalities of the choriocapillaris in exudative age-related macular degeneration.

AIMS: To study the incidence and possible cause of abnormalities of the subfoveal choriocapillaris after surgical excision of subfoveal choroidal neovascularisation in age-related macular degeneration (ARMD). METHODS: The postoperative fluorescein angiograms and colour photographs of 29 eyes of 29 patients were reviewed after surgical excision of subfoveal choroidal neovascularisation in exudative ARMD. Preoperative and postoperative fluorescein angiograms were examined for perfusion of the subfoveal choriocapillaris. The excised subfoveal choroidal neovascular membranes from eight eyes that demonstrated postoperative abnormalities of the choriocapillaris were embedded in paraffin, serially sectioned and examined for the presence of the choriocapillaris. RESULTS: Postoperative fluorescein angiograms revealed abnormal perfusion of the subfoveal choriocapillaris in 26 of the 29 eyes (90%) and in all eight eyes that had histopathological examination of the surgical specimens. Examination of serial sections demonstrated that none of the excised neovascular membranes contained choriocapillaris. CONCLUSIONS: Abnormal perfusion of the subfoveal choriocapillaris was frequently present following removal of the subfoveal neovascular membrane in ARMD. The histopathological study demonstrated that abnormalities of the choriocapillaris were not due to removal of the choriocapillaris at the time of surgery.

ISIS-DME: a prospective, randomized, dose-escalation intravitreal steroid injection study for refractory diabetic macular edema.

Purpose: To determine safety and efficacy of intravitreal triamcinolone acetonide (IVTA) for refractory clinically significant diabetic macular edema (DME). Design: Prospective, randomized, dose-escalation pilot study comparing single injection of 2 mg versus 4 mg doses of IVTA. Methods: Inclusion criteria included clinically significant DME persisting ≥3 months after maximal laser treatment and visual acuity ≤20/40. Best-corrected ETDRS vision, intraocular pressure, presence of DME, and fluorescein angiography (FA) were evaluated at 3 months and 6 months after injection. Results: Mean change in visual acuity at 3 months compared to baseline was 7.1 letters (P = 0.01) in the 2 mg group and 12.5 letters in the 4 mg group (P < 0.0001). However, there was not a significant difference in visual improvement between the 2 mg and 4 mg dose groups (P = 0.11). Vision improved >15 letters at 3 months in 23% (3/13) of 2 mg group and in 33% (5/15) of 4 mg group (P = 0.69), and 0% (0/11) and 21% (3/14) at 6 months, respectively (P = 0.23). Visual improvement was more likely in cystoid-type DME than diffuse DME. Intraocular pressure rise of ≥10 mmHg occurred in 19% (3/16) of 2 mg group and 41% (7/17) of 4 mg group. Conclusions: Both doses of IVTA were well tolerated and had significant positive effects on refractory DME for short term. There were consistent trends throughout the study that suggest that a 4 mg IVTA may be more effective than a 2 mg dose. The benefit of IVTA was greater for cystoid-type DME.

Comparison of topical anesthetics for intravitreal injections : a randomized clinical trial.

Purpose: To determine whether there is a difference in anesthetic effect between topical proparacaine drops, 4% lidocaine solution, or 3.5% lidocaine gel, and whether this has an impact on the overall injection experience. Methods: One hundred and twenty sequential patients undergoing intravitreal injections were randomized to 1 of 3 groups: proparacaine 0.5% drops (Group 1), proparacaine + 4% lidocaine-soaked cotton tipped swabs (Group 2), or 3.5% lidocaine gel (Group 3). Discomfort associated with the lid speculum, with the needle, and with burning sensation was graded on a scale of 0 to 10 (0 = no pain, 10 = worst pain ever). The overall injection experience was graded as Excellent, Very Good, Fair, Poor, or Awful. Results: The average lid speculum pain score for Group 1 was 0.85, Group 2 was 0.50, and Group 3 was 0.65 (P = 0.32). The average needle pain score for Group 1 was 1.78, Group 2 was 1.75, and Group 3 was 1.48 (P = 0.38). The average burning pain score for Group 1 was 1.45, Group 2 was 1.58, and Group 3 was 1.13 (P = 0.23). Overall satisfaction was rated as Excellent or Very Good in 95%, 97.5%, and 92.5% of Group 1, 2, and 3 patients, respectively (P = 0.64). Conclusion: The use of topical proparacaine drops provides very effective and cost-effective anesthesia during office-based intravitreal injections.

The use of topical aqueous suppressants in the prevention of postoperative intraocular pressure elevation after pars plana vitrectomy with long-acting gas tamponade.

OBJECTIVE To determine whether topical aqueous suppressant therapy applied after pars plana vitrectomy with gas tamponade prevents postoperative intraocular pressure (IOP) elevation. DESIGN Prospective, nonrandomized comparative study. PARTICIPANTS Forty-one patients who met inclusion criteria and underwent pars plana vitrectomy with gas tamponade (SF6 18%-20% or C3F8 12%-16%) over a 1-year period. INTERVENTION Treatment eyes received topical aqueous suppressants at the end of surgery. MAIN OUTCOME MEASURES Postoperative IOP at 4 to 6 hours, 1 day, and 1 week. RESULTS Twenty-one control and 20 treatment eyes met the inclusion criteria. The IOP (in mmHg) measured at 4 to 6 hours (23.05 [control, 14.73 [treatment]) and 1 day (23.24 [control], 17.28 [treatment]) postoperatively showed a statistically significant difference between the groups (P = 0.0038) at 4 to 6 hours and a trend toward significance (P = 0.057) at 1 day. Eleven control and three treatment eyes had an IOP spike above 25 mmHg at 4 to 6 hours or 1 day postoperatively (P = 0.02), and six control eyes and one treatment eye had postoperative IOP greater than 30 mmHg. A pressure rise greater than 40 mmHg was seen in two control eyes and no treatment eyes. CONCLUSIONS Use of topical aqueous suppressants after pars plana vitrectomy with long-acting gas tamponade is effective in preventing significant postoperative IOP elevation in most cases.

Comparison of Aflibercept, Bevacizumab, and Ranibizumab for Treatment of Diabetic Macular Edema: Extrapolation of Data to Clinical Practice.

IMPORTANCE The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study. OBJECTIVES To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment. EVIDENCE REVIEW The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013. FINDINGS On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment. CONCLUSIONS AND RELEVANCE On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.

Sustained postoperative face-down positioning is unnecessary for successful macular hole surgery

Aim: To determine the rate of successful macular hole closure with 1-day postoperative prone positioning Methods: Multicentre review of all consecutive cases of stage 3 and 4 macular hole surgery performed during a 15-month period employing 1-day postoperative face-down positioning regimen. Cataract surgery was not routinely combined with macular hole surgery. Internal limiting membrane peeling was employed in all but seven eyes. Either SF6 or C3F8 gas tamponade was used. The primary outcome assessed was the rate of hole closure. Results: 56 eyes of 53 patients were identified. 79% of eyes had stage 3 macular holes, and 39 of 56 (70%) eyes were phakic at the time of surgery. The mean preoperative logMAR vision was 0.74 (∼20/100 Snellen) and mean postoperative logMAR vision was 0.41 (∼20/50 Snellen) with a mean follow-up period of 5.2 months. Macular hole closure was achieved in 52 eyes (93%) with one operation. Conclusion: Sustained postoperative face-down positioning may not be necessary for successful macular hole closure, since 93% of eyes achieved hole closure with prone positioning for only 1 day.

Failure of intravitreal dexamethasone to diminish inflammation or retinal toxicity in an experimental model of Bacillus cereus endophthalmitis

Purpose. To determine whether the usual clinical dose of intravitreal dexamethasone can attenuate intraocular inflammation and retinal necrosis in a rabbit model of fulminant Bacillus cereus endophthalmitis induced by crude exotoxins. Methods. Thirty-six eyes from pigmented mongrel rabbits received intravitreal injections of varying concentrations of crude B. cereus exotoxins with or without concomitant injections of 400 µg of dexamethasone sodium phosphate (0.1% solution). After ophthalmoscopic examination at 4 or 18 hr postinjection, the animals were killed and histopathologic findings graded. Results. Intraocular inflammation and retinal necrosis scores in eyes receiving both exotoxins and dexamethasone did not differ significantly from eyes receiving exotoxins alone for any exotoxin dose at 4 or 18 hr. The severity of retinal necrosis increased with toxin dose and was nearly maximal after 4 hr. Intraocular inflammation also generally increased with dose, but continued to increase until 18 hr. Conclusions. Standard clinical doses of intravitreal dexamethasone do not appear to attenuate the intraocular inflammatory or tissue response to secreted B. cereus exotoxins. Other treatment modalities including vitrectomy, to decrease exotoxin load, and exotoxin inhibitors may be necessary for the effective treatment of B. cereus endophthalmitis.