Irit Rosenblatt

Cystoid macular edema after cataract surgery with intraocular vancomycin

OBJECTIVE To determine whether the use of supplemental prophylactic vancomycin in the irrigating solution during extracapsular lens extraction is associated with increased incidence of cystoid macular edema. DESIGN Prospective, randomized, double-masked clinical study. PARTICIPANTS Consecutive series of 118 patients 60 years of age or older undergoing cataract surgery. INTERVENTION The study group received an irrigating balanced salt solution supplemented with vancomycin (10 microg/ml), and the control group received the salt solution only. Fluorescein angiography was performed 1 and 4 months after surgery. MAIN OUTCOME MEASURES Evidence of angiographic and clinical cystoid macular edema, and visual acuity at 1 and 4 months after surgery. RESULTS The rate of postoperative angiographic cystoid macular edema was significantly higher in the study patients than in the control group at 1 month (55% vs. 19%, P = 0.0006) and 4 months (26% vs. 4%, P = 0.0099). The rates of clinical macular edema were 23% and 7%, respectively, at 1 month (P = 0.011) and 20% versus 0% at 4 months (P = 0.006). Visual acuity of 20/30 or better was noted at 4 months after surgery in 76% of the study group compared to 95.5% of the control group. CONCLUSIONS The role of preventive intracameral vancomycin during intraocular surgery should be reassessed in view of the associated increase in the incidence of angiographic cystoid macular edema.

Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study).

PURPOSE To evaluate the safety and efficacy of three doses of PF-04523655, a 19-nucleotide methylated double stranded siRNA targeting the RTP801 gene, for the treatment of diabetic macular edema (DME) compared to focal/grid laser photocoagulation. METHODS This multicenter, prospective, masked, randomized, active-controlled, phase 2 interventional clinical trial enrolled 184 DME patients with best corrected visual acuity (BCVA) of 20/40 to 20/320 inclusive in the study eye. Patients were randomly assigned to 0.4-mg, 1-mg, 3-mg PF-04523655 intravitreal injections or laser. The main outcome measure was the change in BCVA from baseline to month 12. RESULTS All doses of PF-04523655 improved BCVA from baseline through month 12. At month 12, the PF-04523655 3-mg group showed a trend for greater improvement in BCVA from baseline than laser (respectively 5.77 vs. 2.39 letters; P = 0.08; 2-sided α = 0.10). The study was terminated early at month 12 based on predetermined futility criteria for efficacy and discontinuation rates. PF-04523655 was generally safe and well-tolerated, with few adverse events considered treatment-related. By month 12, the discontinuation rates in the PF-04523655 groups were higher than the laser group and were inversely related to dose levels. CONCLUSIONS PF-04523655 showed a dose-related tendency for improvement in BCVA in DME patients. Studies of higher doses are planned to determine the optimal efficacious dose of PF-04523655. PF-04523655 may offer a new mode of therapeutic action in the management of DME. (ClinicalTrials.gov number, NCT00701181.).

Evaluation of the siRNA PF-04523655 versus Ranibizumab for the Treatment of Neovascular Age-related Macular Degeneration (MONET Study)

OBJECTIVE To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). DESIGN Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. PARTICIPANTS A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. METHODS In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. MAIN OUTCOME MEASURES The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining ≥ 10 and ≥ 15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. RESULTS At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained ≥ 10 and ≥ 15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. CONCLUSIONS In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified.

Pneumatic Displacement of Submacular Hemorrhage due to Age-Related Macular Degeneration

Purpose: Subretinal hemorrhage is one of the most serious complications of exudative age-related macular degeneration (AMD). Treatment with vitreous surgery with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon yields only a small improvement in visual acuity. Patients and Methods: The files of 24 patients with submacular hemorrhage secondary to AMD who were treated by injection of perfluoropropane gas (C3F8) (11 patients) or sulfur hexafluoride (SF6) (13 patients) were reviewed for visual acuity before and after the procedure and time of treatment from onset of symptoms. Results: For the whole sample, pneumatic displacement led to a statistically significant improvement in mean visual acuity (p = 0.015). A significant difference between pre- and postoperative visual acuity was found for the patients treated with SF6 (p = 0.034), but not for the patients treated with C3F8 (p = 0.245). Conclusion: The use of gas injection to displace submacular hemorrhage can significantly improve visual acuity.

Indocyanine Green Angiography in High Myopia

BACKGROUND AND OBJECTIVE To evaluate indocyanine green imaging of choroidal changes in pathologic myopia and to compare it with fluorescein angiography. PATIENTS AND METHODS The angiograms of all consecutive patients with pathologic myopia photographed with confocal indocyanine green angiography using a scanning infrared laser or ophthalmoscope from March 1997 to December 1999 were reviewed. RESULTS Twenty-one patients (35 eyes) were included. Indocyanine green angiography was performed in 35 eyes and immediate sequential fluorescein angiography and indocyanine green angiography in 25 eyes. The lacquer cracks were demonstrated to radiate from the disc, at the papillomacular bundle, through the macula, and around the macula. Lacquer cracks were identified in 89% and 28% of the eyes, respectively. Choroidal neovascularization (CNV) was demonstrated in 57% of eyes by indocyanine green angiography and in 56% by fluorescein angiography. All of the CNVs were classic and were located within 300 microm of the foveal center. Seventy percent of the CNVs were delineated in lacquer cracks by indocyanine green angiography. Overall, 124 lacquer cracks were identified by indocyanine green angiography and only 14 by fluorescein angiography. Lipids or serous detachment were not observed. Retinal hemorrhages were noted in 22% and 28% of eyes with indocyanine green angiography and fluorescein angiography, respectively. CONCLUSION Confocal indocyanine green angiography offers better delineation of lacquer cracks and the localization of the CNV in lacquer cracks than does fluorescein angiography.

Interferon alpha-2a for proliferative diabetic retinopathy after complete laser panretinal photocoagulation treatment.

BACKGROUND AND OBJECTIVE The aim of this study was to investigate the effect of interferon alpha-2a, an angiogenesis inhibitor, on eyes with active neovascularization after complete laser panretinal photocoagulation treatment. PATIENTS AND METHODS Eight patients with active neovascularization persisting for 6 months or more after completion of full panretinal photocoagulation were included in the study. All patients were treated with subcutaneous injections of 6 million international units of interferon alpha-2a, 3 times a week, for an average period of 10 months. Visual acuity, contrast sensitivity, blood tests, fundus photographs, fluorescein angiography, and physical examination were performed periodically. The main outcome measures were visual acuity and extent of neovascularization as assessed by fundus photography and fluorescein angiography. RESULTS The 5 men and 3 women (mean age, 60 years) had a mean duration of diabetes of 19 years. The average study follow-up was 42.2 +/- 8.7 weeks. Visual acuity and extent of neovascularization improved or remained stable in 7 patients. In none of the patients was there progression of neovascularization, but in 1 patient it could not be assessed due to vitreous hemorrhage. Most patients had malaise during the first weeks of treatment, but none of the patients suffered from nonreversible side effects associated with interferon alpha-2a. CONCLUSION This pilot study provides evidence that interferon alpha-2a might have a role in the regression of proliferative diabetic retinopathy and that further investigation is warranted.

Combined photodynamic therapy and intravitreal triamcinolone acetonide injection for neovascular age-related macular degeneration with pigment epithelium detachment.

The authors report a case of acute development of an extensive retrobulbar abscess 3 weeks after an orbital floor fracture. Urgent drainage of the abscess was performed by an anterior transconjunctival approach. A dramatic recovery was observed a few days following the operation. The visual acuity increased from hand motions to 0.7 to 0.8 in the early postoperative period and to 1.0 shortly thereafter. The severity of infection, the importance of antibiotic prophylaxis for blowout fractures, and the efficacy of the transconjunctival approach on the final visual and functional outcome are described.A 38-year-old man with human immunodeficiency virus was referred for evaluation of retinal lesions in both eyes. Optical coherence tomography was performed after dilating the pupils. Biomicroscopy of the retina showed an atypical, solitary, yellowish-white lesion in the macula of both eyes with no inflammation of the vitreous. Optical coherence tomography of the lesions showed an area of extremely low reflectivity with well-defined but irregular borders in the outer retina. The surrounding retina showed normal reflectivity and was of normal thickness. Optical coherence tomography showed selective necrosis of the outer layers due to progressive outer retinal necrosis. Optical coherence tomography may serve as a useful tool for the early diagnosis of progressive outer retinal necrosis.

Simultaneous indocyanine green and fluorescein angiography in retinal pigment epithelium tear using the confocal scanning laser ophthalmoscope

PURPOSE To describe the indocyanine green angiographic pattern of retinal pigment epithelium tears in the setting of age-related macular degeneration compared with the fluorescein angiographic features. METHODS Twelve consecutive patients (12 eyes) with a retinal pigment epithelium tear underwent simultaneous indocyanine green angiography and fluorescein angiography with the confocal scanning laser ophthalmoscope. The findings for the two modes were compared. RESULTS Choroidal neovascular membrane was evident beneath the rolled retinal pigment epithelium on indocyanine green angiograms in 11(92%) of 12 eyes: a focal neovascular membrane was apparent in five (42%) of 12 eyes, whereas a plaque neovascular membrane was seen in six (50%) of 12 eyes. In comparison, fluorescein angiography demonstrated late leakage as a result of occult choroidal neovascular membrane in nine (82%) of 11 eyes but no well-defined choroidal neovascular membrane. CONCLUSIONS Indocyanine green angiography is superior to fluorescein angiography for imaging choroidal neovascularization in cases of retinal pigment epithelium tear and may serve as an important adjunct to indocyanine green-guided laser treatment in selected cases.

Combined Pars Plana Vitrectomy and Cataract Surgery: Outcome of Phacoemulsification Versus Manual Extracapsular Cataract Extraction Through a Sclerocorneal Tunnel

BACKGROUND AND OBJECTIVE To compare the results of combined pars plana vitrectomy and cataract extraction with intraocular lens implantation by phacoemulsification versus manual extracapsular cataract extraction through a sclerocorneal tunnel. PATIENTS AND METHODS Retrospective chart review of all patients who underwent combined pars plana vitrectomy with intraocular lens implantation and phacoemulsification or extracapsular cataract extraction through a sclerocorneal tunnel between March 1992 and July 2002. RESULTS Fifty-four eyes of 51 patients were evaluated. Mean age was 69.68 +/- 9.11 years, and mean follow-up was 9 months. Phacoemulsification was performed in 35 cases (64%) and manual extraction in 19 cases (36%). Visual acuity improved from mean logarithm of the minimal angle of resolution 1.69 +/- 0.54 before surgery to 1.22 +/- 0.76 after surgery. There was a greater improvement of visual acuity in the phacoemulsification group (0.59 +/- 0.67) than in the extracapsular cataract extraction group (0.22 +/- 0.68) (P = .06). Final visual acuity was correlated to the vitreoretinal pathology. Ultrasound biomicroscopy showed well-positioned foldable or rigid intraocular lens in the bag or in the sulcus. CONCLUSION Combined cataract extraction by phacoemulsification or extracapsular cataract extraction through sclerocorneal tunnel and pars plana vitrectomy are safe and effective procedures.