Gerardo Garcia-Aguirre

Long-term effect of antiangiogenic therapy for retinopathy of prematurity up to 5 years of follow-up.

Purpose: To evaluate ocular function and systemic development in premature infants treated with intravitreal bevacizumab injections for retinopathy of prematurity over a period of 5 years. Methods: A prospective, interventional, noncomparative case study. The primary outcome measure was visual acuity. The secondary outcomes were structural assessment, other ocular functional measurements, and developmental state. Results: Eighteen eyes of 13 consecutive patients were divided into 3 groups: Group 1, Stage 4 unresponsive to previous conventional treatment (n = 4); Group 2, in which conventional treatment was difficult or impossible because of inadequate visualization of the retina (n = 5); and Group 3, newly diagnosed high-risk prethreshold or threshold retinopathy of prematurity (n = 9). All patients showed initial regression of neovascularization. One patient was diagnosed with recurrence of neovascularization and was treated with intravitreal bevacizumab. Visual acuity was preserved, and median vision was 20/25 (excluding 2 operated eyes). Twelve eyes developed mainly low myopia over the years, with an overall mean value of 3.2 diopters. Electroretinograph was normal in 4 eyes that had no previous detachment. One patient showed delay in growth and neurodevelopment, whereas all the others were within the normal range. Conclusion: Five years of follow-up in a small series suggest that intravitreal bevacizumab for retinopathy of prematurity results in apparently preserved ocular function and systemic development.

Short-term outcome after intravitreal ranibizumab injections for the treatment of retinopathy of prematurity

Purpose To evaluate ocular outcome in premature infants treated with intravitreal ranibizumab injections for retinopathy of prematurity (ROP) over a period of 3 years. Methods An interventional case series. Premature infants with high-risk prethreshold or threshold ROP with plus disease received an off label monotherapy with intravitreal injections of ranibizumab. The primary outcome was treatment success defined as regression of neovascularisation (NV) and absence of recurrence. The secondary outcomes were ocular and systemic adverse events and visual acuity. Results Six eyes were included in the study and treated with intravitreal injections of ranibizumab. All showed complete resolution of NV after a single injection. The anti-angiogenic intravitreal injections allowed for continued normal vessel growth into the peripheral retina, without any signs of disease recurrence or progression during the follow up period. No ocular or systemic adverse effects were observed. Conclusions Three years of follow up in a small series suggest that intravitreal ranibizumab injections for ROP result in apparently preserved ocular outcome. Further large scale studies are needed to address the long-term safety and efficacy.

Retinal fluorescein angiographic changes following intravitreal anti-VEGF therapy

PURPOSE To describe the retinal vascular morphology in eyes injected with intravitreal bevacizumab for treatment-requiring retinopathy of prematurity (ROP). METHODS In this prospective, nonrandomized case series, fundus photographs and fluorescein angiography in patients diagnosed with stage 3 threshold or prethreshold ROP, were obtained immediately before and 1 month after injection of 0.03 cc (0.75 mg) of intravitreal bevacizumab using wide-field digital pediatric imaging system. RESULTS A total of 47 eyes of 26 patients were included. Before treatment, fluorescein angiography showed vascular abnormalities, including capillary nonperfusion throughout and shunting in the vascularized retina, demarcation line, limited vessel development, new vessels leakage, avascular periphery and absence of foveal avascular zone. After intravitreal bevacizumab, fluorescein angiography showed involution of the neovascularization, flattening of the demarcation line and subsequent growth of vessels to the capillary-free zones. During the following weeks large areas devoid of microvessels were seen as well as vascular remodeling with uneven spacing of the retinal capillaries and vascular loops in the areas that were previously devoid of vessels. In some patients, retinal vessels in the far periphery never developed: patients with these findings did not subsequently develop pathological neovascularization. CONCLUSIONS In this study cohort, patients showed improvement of their abnormal vascular findings after intravitreal bevacizumab, however even when the vascular pattern remained abnormal, there was creation of small vessels, establishment of directional flow, maturation of retinal vessels, and adjustment of vascular density.

Prevalence of macular anatomic abnormalities in high myopia.

BACKGROUND AND OBJECTIVE Macular anatomic abnormalities in high myopia are more frequent in the presence of posterior staphyloma. The objective was to determine the prevalence of foveoschisis, foveal detachment, vascular traction, epiretinal membrane (ERM), and macular hole (MH) in eyes with high myopia by spectral-domain optical coherence tomography. PATIENTS AND METHODS Prospective, observational study. Eyes with myopia greater than 8 diopters (D) were included. Results were analyzed using chi-square and Students t tests. RESULTS The study included 116 eyes of 72 patients. Mean spherical equivalent: -15.04 ± 5.33 D. Mean axial length: 28.88 ± 2.31 mm. Foveoschisis was observed in 17 eyes (14.65%), vascular traction in 17 (14.65%), ERM in 13 (11.2%), lamellar MH in two (1.72%), and posterior staphyloma in 41 (35.34%). Presence of foveoschisis, vascular traction, and ERM was more frequent in eyes with posterior staphyloma (P = .0001). CONCLUSION Macular anatomic abnormalities were observed in 22.41% of eyes with high myopia and in 53.65% of eyes with posterior staphyloma.

Perfluorocarbon-perfused vitrectomy using a transconjunctival 25-gauge system.

Purpose: To describe the feasibility of perfluorocarbon-perfused vitrectomy (PCPV) using a 25-gauge system in complicated retinal detachment cases. Methods: Thirteen nonconsecutive patients with complicated retinal detachment (either tractional secondary to proliferative diabetic retinopathy or rhegmatogenous) who would not normally be selected for 25-gauge vitrectomy were included in the study. Vitrectomy using 25-gauge ports and perfluorocarbon perfusion was performed. Real vitrectomy time, amount of perfluorocarbon liquid (PCL) used, instrument bending, feasibility of surgical maneuvers using an arbitrary scale, and anatomical and visual results were evaluated. Results: Real vitrectomy time ranged from 6.2 minutes to 17.1 minutes (mean, 10.3 minutes). Amount of PCL ranged from 8 mL to 40 mL (mean, 24.38 mL). Instruments never bent even when using a wide-angle sutured contact lens. All desired maneuvers could be performed and were facilitated by PCL. All retinas were reattached, with two cases of mild recurrent vitreous hemorrhage. Visual acuity improved in 76.9% of eyes. Conclusions: PCPV using a 25-gauge system can be performed, even in complicated cases.

Growth of Scytalidium sp. in a counterfeit bevacizumab bottle.

After drawing a dose from an closed bevacizumab (Avastin) bottle, a fungus-like foreign body was observed inside. Samples from the vial were cultured in Sabouraud Emmons media. Growth of multiple light brown colonies with dark pigment was observed after 10 days. The species was identified as Scytalidium sp. Vial, analysis reported that the seal was lacking proper identification measures and that the label, batch number and expiry date did not correspond to a genuine product. Chemical analysis showed no protein, but 3% of polyethylene glycol, citrate and ethanol. Counterfeit bevacizumab is a real situation that poses a significant risk for ophthalmology and oncology patients. The medical community should be aware of this situation in order to enforce adequate preventive measures.

Intravitreal bevacizumab versus panretinal photocoagulation for treatment-naïve proliferative and severe nonproliferative diabetic retinopathy

floxacin 400 mg od po for 10 days. Prednisolone 1 mg ⁄kg od po was commenced after one day, providing the presence of fungi had been excluded on microscopy. Subsequent management depended on clinical course: a second intravitreal injection of the same antibiotics was performed at 48 hr if there was no improvement; vitrectomy was considered if there was no improvement after a further 48 hr. The primary outcome measure was the proportion of patients achieving a final best-corrected visual acuity (BCVA) of 20 ⁄ 40 or better. Seventy-two eyes of 72 patients were included in the study. The mean followup was 18 weeks (range, 8–150 weeks). Forty-eight patients were treated with ciprofloxacin and 24 with moxifloxacin. There were no significant differences between the two groups in terms of patient and surgical characteristics. Of the 72 cases, six (8%) were culture positive from the anterior chamber tap alone, 35 (49%) from the vitreous tap alone and 31 (43%) from both samples. The most common bacterial isolate was coagulase-negative staphylococci (CNS) (45 eyes, 63%). All Gram-negative organisms were susceptible to amikacin, and 98% of Gram-positive isolates were susceptible to vancomycin. Resistance to ciprofloxacin increased over the course of the study from 18% in 2000–2004 to 37% in 2005– 2009 (p = 0.04); only one isolate was resistant to moxifloxacin. Of the 72 eyes, 28 (39%) had a final BCVA of 20 ⁄ 40 or better, and 53 (74%) had a final BCVA of 20 ⁄ 200 or better. There were no recorded complications of ciprofloxacin or moxifloxacin. Resolution of hypopyon occurred quicker in the moxifloxacin group (mean, 2.6 days versus 4.3 days; p = 0.006), and there was a reduced need for repeat intravitreal injections (2 ⁄ 24 eyes (8%) versus 18 ⁄ 48 eyes (39%); p = 0.01), but not vitrectomy (5 ⁄ 24 eyes (21%) versus 6 ⁄ 48 eyes (13%); p = 0.49). Table 1 summarizes factors associated with having a final BCVA of 20 ⁄ 40 or better. In the univariate analyses, only a microbiological diagnosis of CNS was statistically significantly associated with good visual outcome. After controlling for potentially confounding variables including ciprofloxacin resistance, the detection of CNS and the use of oral moxifloxacin were all associated with a good visual outcome (OR for moxifloxacin, 4.07; p = 0.035). The role of systemic antibiotics in the management of acute-onset bacterial endophthalmitis following cataract surgery is controversial. The EVS reported that intravenous amikacin and ceftazidime made no difference to final visual acuity (Endophthalmitis Vitrectomy Study Group 1995), but, despite newer antibiotics with improved ocular penetration having become available, no large study has subsequently readdressed this question. Our study suggests that adjunctive moxifloxacin can have a beneficial impact on the clinical course of the infection and lead to an improved clinical outcome. To our knowledge, this is the first study to provide such evidence of the benefit of adjunctive oral antibiotics in this setting.

Tractional retinal detachment after intravitreal injection of bevacizumab in proliferative diabetic retinopathy.

PURPOSE To assess the short-term complications of a single dose of intravitreal bevacizumab in patients with proliferative diabetic retinopathy (PDR). METHODS Retrospective review of 343 patients with PDR who were treated with intravitreal injection of bevacizumab (2.5 mg/0.1 mL). RESULTS Five patients (1.45%) presented tractional retinal detachment 1 to 6 weeks (mean 3 weeks) after intravitreal injection. All cases underwent pars plana vitrectomy, removal of all epiretinal fibrovascular membranes, further endolaser panretinal photocoagulation, and silicone tamponade. CONCLUSION Tractional retinal detachment may occur in a short time post intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy with extensive areas of ischemia and fibrovascular proliferations, and may require prompt vitreoretinal surgery.

Comparison of iridocorneal angle in infants with retinopathy of prematurity and healthy infants using spectral domain optical coherence tomography.

PURPOSE To compare measurements and morphologic characteristics of the iridocorneal angle in preterm infants with retinopathy of prematurity (ROP) and healthy infants using spectral domain optical coherence tomography (SD-OCT). METHODS In this observational, case-control study, the eyes of children with ROP and healthy controls under 1 year old were imaged using SD-OCT without sedation to capture the iridocorneal angle. The ROP staging was made by a pediatric retinal specialist. The following measurements were analyzed with custom software: angle opening distance (AOD500) at 500 μm; angle opening in degrees (AOG); and angle recess area (ARA750). RESULTS A total of 27 eyes of 14 children with ROP and 21 of 13 children without ROP were included. The mean gestational age of children in the ROP group was 30 weeks; of the controls, 35 weeks. The mean birth weight in the ROP group was 1,545 g; in the non-ROP group 2,100 g. Mean age at the time of the study was 18.1 (ROP group) vs 25.7 weeks (non-ROP). In the ROP group AOD500 was 477 μm (95% CI, 358-597 μm), AOG was 37.3° (95% CI, 30.4°-44.3°), and ARA750 was 231 mm(2) (CI 95%, 171-291 mm(2)). The same parameters on the non-ROP group were 400 μm (CI 95% 333-468 μm), 34.7° (CI 95% 30.4°-39°), and 203 mm(2) (95% CI, 171-236 mm(2)). The iris showed a more convex pattern on eyes with ROP (56% vs 23%). CONCLUSIONS In this study cohort, children with ROP showed higher AOD500, AOG, and ARA750, perhaps because of different patterns of physiological development in children with ROP.

Bevacizumab Local Complications

Dear Editor: Bevacizumab (Avastin, Genetech, San Francisco, CA) is a recombinant monoclonal antibody (IgG1) that selectively binds and neutralizes the biological activity of vascular endothelial growth factor. Its intravenous administration was approved by the Food and Drug Administration (FDA) in February 2004 as a first-line therapy for metastatic colorectal cancer. In the past few years, “off-label” uses in the ophthalmology field have become popular due to its encouraging results in the treatment of vasoproliferative diseases. While no one disputes its apparent effectiveness, the relative effectiveness compared with ranibizumab, and the safety of its intravitreal administration, has recently been debated. This is due to lack of comparative data from large prospective randomized trials, and in part, because of doubts cast by the warnings issued by the FDA and the manufacturer about possible local and systemic adverse effects (AE). One cause of confusion lies in the multiple AEs reported after intravenous administration (dose of 5 mg/kg). Even though the intravitreal doses are almost 400 times smaller than the intravenous, there is some systemic absorption of the drug (3.3 mg/ml, 8 days after intravitreal injection). The fact that this amount of bevacizumab may produce systemic AEs is a major concern for the retinal specialists. Due to the lack of information in the literature regarding the incidence of local complications after its intravitreal administration; we decided to review our experience in the use of this antibody. Our study was approved by the hospital ethics board. We reviewed the clinical records of 3517 consecutive injections in 2863 patients, in a period of time involving 27 months (September 2005 to December 2007). We included all bevacizumab injections, regardless the pretreatment diagnosis or the intravitreal dose. For every case, we recorded the age, gender, diagnosis, type of AE, drug dose, number of injections, best corrected visual acuity (BCVA) before the AE, BCVA in the last follow up, the time between the intravitreal injection and the diagnosis of the AE, the need for surgery, the time until the AE was resolved, and time of follow-up (follow-up time). We also recorded the blood pressure before and after the injection. Descriptive analyses were performed using SPSS software, version 10.1.0 (SPSS Inc., Chicago, IL). We identified 16 AEs that appeared to be directly related to the administration of intravitreal bevacizumab. The general demographic data is summarized in Table 1 (available at http://aaojournal.org). The dose used in all patients was 2.5 mg. Most of the patients had previous injections but not always in the same eye. Only 2 patients had 1 or more injections in the same eye (2 females, 1 developed endophthalmitis and the second developed a tractional retinal detachment). Two male patients (0.05%) presented with anterior chamber inflammation (anterior chamber cells 2 ), without other clinical sign of infection. Neither of these 2 cases required surgery or additional treatment beside topical nonsteroidal anti-inflammatories. Four female and 2 male patients presented endophthalmitis (0.17%). The mean time between the intravitreal injection and the development of the en-