October Literature Roundup
Patient Literature Roundup
- Amol Kulkarni, MD
- Michael M. Altaweel, MD, Section Co-Editor
- Asheesh Tewari, MD, Section Co-Editor
A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema: 24-Month Data: Report 3
[published online ahead of print April 9, 2012]
Rajendram R, Fraser-Bell S, Kaines A, et al. Arch Ophthalmol. 2012;130(8):972-979. doi:10.1001/archophthalmol.2012.393.
The Early Treatment Diabetic Retinopathy Study (ETDRS) showed that macular laser photocoagulation decreased the risk of vision loss of 15 letters due to clinically significant macular edema (CSME) by 50% compared with eyes that did not receive treatment. However, there is a subset of patients unresponsive to this therapy. Intravitreal injections with bevacizumab have been demonstrated to be safe and effective for treating persistent diabetic macular edema (DME) despite laser treatment.
The Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema study is a prospective, randomized controlled trial evaluating the role of intravitreal bevacizumab and modified ETDRS macular laser therapy (MLT) in patients with persistent DME. The study consisted of 80 patients with center-involved DME who had previously received focal laser and had visual acuity of 20/40 to 20/320.
Patients were randomly assigned to a bevacizumab arm receiving injections every 6 weeks for the first 3 months and every 6 weeks as needed thereafter, and a laser arm receiving as-needed macular laser every 4 months. At 2 years, the bevacizumab arm gained a median of 9 ETDRS letters vs 2.5 letters for laser group. Forty-nine percent of patients treated with bevacizumab gained 10 or more letters as compared with 7% in the laser group. The median number of treatments over 24 months was 13 for bevacizumab and 4 for laser. A mean of 4 injections were required in the second year.
Application to Practice: Persistent center-involving macular edema despite previous laser photocoagulation is a common clinical dilemma faced by practitioners. The BOLT trial specifically focused on this subgroup with persistent DME; results support the longer term use of bevacizumab. This trial reconfirms that the benefits of laser photocoagulation may not be fully realized until at least the second year of follow-up.
Relevance to Patients: Intravitreal bevacizumab (Avastin) can be safely used on a long-term basis for treatment of diabetic macular edema.
Effect of Combination Therapy With Bevacizumab and Dexamethasone Intravitreal Implant in Patients With Retinal Vein Occlusion
Singer MA, Bell DJ, Woods P, et al. Retina. 2012;32(7):1289-1294. doi:10.1097/IAE.0b013e318242b838.
Retinal vein occlusions (RVOs) cause macular edema (ME), which can be treated with laser photocoagulation and/or intravitreal pharmacotherapy. The intravitreal medications available include triamcinolone, dexamethasone intravitreal implant (Ozurdex; Allergan, Inc, Irvine, CA), and ranibizumab (Lucentis; Genentech, Inc, South San Francisco, CA), as described in the SCORE, OZURDEX GENEVA, and BRAVO/CRUISE studies respectively. Bevacizumab has also been shown to be efficacious in the treatment of ME secondary to RVO.
This prospective, interventional case series consisted of 34 eyes of 33 patients with ME associated with RVO who were injected with bevacizumab, followed by dexamethasone intravitreal implant injection 2 weeks later. These patients were reexamined monthly and retreated with bevacizumab when ME recurred during the 6-month study period.
The primary outcome measure was the time to reinjection based on OCT and vision criteria. Thirty-five percent of patients had central RVO (CRVO) and 65% had branch RVO (BRVO); 82% (28 of 34) needed at least 1 more injection before month 6, while 18% (6 of 34) did not need an additional injection of bevacizumab.97% of patients gained vision during the study, and mean visual acuity improved from initially 11 letters to a maximum of 25 letters during the study period. OCT showed macular thickness decreased with the combination treatment, and the effect continued an average of 126 days from the initial bevacizumab treatment.
Eighteen percent (6 of 34) of patients had an IOP of 23 mmHg or greater. Five of these 6 subjects were controlled with drops alone, while one required an additional selective laser trabeculoplasty. This study demonstrates efficacy and the duration of effect using a combination of bevacizumab and dexamethasone vs dexamethasone alone. The combination is synergistic, increasing visual acuity and prolonging the time between injections, compared with either medication alone.
Application to Practice: Various treatment options are available for treatment of macular edema associated with RVO. This study demonstrates that the combination of a vascular endothelial growth factor inhibitor and a dexamethasone implant may be a valuable option for RVO treatment. The study design is applicable to many patients with persistent ME secondary to RVO in the typical ophthalmology practice.
Relevance to Patients: Ozurdex implant can be considered in combination with intravitreal anti-VEGF agents for treatment of persistent macular edema secondary to retinal vein occlusion.
Risk for Retinal Detachment After Phacoemulsification: A Whole-Population Study of Cataract Surgery Outcomes
Clark A, Morlet N, Ng JQ, Preen DB, Semmens JB. Arch Ophthalmol. 2012;130(7):882-888. doi:10.1001/archophthalmol.2012.164.
There is 1% overall incidence of retinal detachment (RD) following cataract surgery. The risks include patient factors (younger age, male sex, and long axial length), surgical factors (operative technique, vitreous loss, and posterior capsule rupture), and postoperative factors (Nd:YAG laser posterior capsulotomy). There has been a significant reduction in incidence of RD subsequent to adoption of phacoemulsification compared with intracapsular cataract extraction.
The long-term risk for RD after phacoemulsification was studied in the entire Western Australia (WA) population using validated linked health administrative data from January 1989 to December 2001. Kaplan-Meier analysis was used to calculate a cumulative incidence (CI) of RD as a percentage of cataract procedures. Cox proportional hazards regression modeling was used to calculate hazard ratios (HRs), which were95% CIs for each risk factor examined.
There were 237 RD cases following 65,055 phacoemulsification procedures, with a 10-year cumulative incidence of 0.68%. Significant risk factors were year of surgery (hazard ratio, 0.43; 95% CI, 0.28-0.66 [1999-2001 compared with 1989-1993] for each 5-year period after 1985), age younger than 60 years, male gender, and anterior vitrectomy.
Hospital location, patient rural or remote locality, hospital cataract surgery volume, failed intraocular lens insertion, length of stay, and patient insurance status were not significantly associated with RD. The axial length and need for Nd:YAG laser posterior capsulotomy in the RD cases were not examined. Thus, risk for RD after phacoemulsification has almost halved for each 5-year period since its adoption in the mid-1980s. Younger patient age and male gender significantly increased risk for RD. Phacoemulsification requiring anterior vitrectomy vastly increased risk for RD.
Application to Practice: Pseudophakic RD is a rare, sight-threatening complication following phacoemulsification cataract surgery. Complicated cataract surgical procedures necessitating anterior vitrectomy carry significantly increased risk for RD. The study emphasizes the important risk factors for subsequent RD. A thorough knowledge of these risk factors is important for physicians to guide preoperative counseling and postoperative review with patients.
Relevance to Patients: Retinal detachment is rare complication after phacoemulsification cataract surgery.
Enhanced Depth imaging Optical Coherence Tomography of Small Choroidal Melanoma: Comparison With choroidal Nevus
Shields CL, Kaliki S, Rojanaporn D, Ferenczy SR, Shields JA. Arch Ophthalmol. 2012;130(7):850-856. doi:10.1001/archophthalmol.2012.1135.
The clinical differentiation of small choroidal melanoma from benign choroidal nevus can be challenging, especially when lesion thickness is 3 mm or less. The various ophthalmoscopically visible factors include greater tumor thickness, the presence of subretinal fluid, overlying lipofuscin, tumor margin near the optic disc, and the absence of drusen and halo.
OCT can be used for detection of subretinal fluid; however, little detail is apparent within the tumor or surrounding choroid. Recent improvements in enhanced depth imaging spectral-domain OCT (EDI-SD-OCT) allow for better imaging of choroidal detail.
The retrospective comparative analysis consisted of 37 eyes with small choroidal melanoma and 51 eyes with choroidal nevi imaged using EDI-SD-OCT. The mean tumor thickness was 1025 μm by EDI-SD-OCT, compared with 2300 μm by ultrasonography. The choroidal features included optical shadowing and thinning of overlying choriocapillaris. There was subretinal fluid in 92%, and subretinal lipofuscin deposition in 95%.
In comparison with similar-sized choroidal nevus, the statistically significant EDI-SD-OCT features for small choroidal melanoma include intraretinal edema (P = .003), shaggy photoreceptors or loss of photoreceptors (P = .005), loss of external limiting membrane (P = .008), loss of inner segment-outer segment junction (P = .02), irregularity of inner plexiform layer (P = .04), and irregularity of ganglion cell layer (P = .04) (t test and χ2 test).
The term shaggy photoreceptors describes the irregular, elongated, and presumed swollen photoreceptors from fresh subretinal fluid. Shaggy photoreceptors were found overlying small choroidal melanoma in 18 eyes (49%), but were not observed overlying choroidal nevus (P < .001). Thus, EDI-SD-OCT provides in vivo quantification of tumor dimensions and cross-sectional detail of the tumor and surrounding choroidal tissues that previously were not depicted.
Application to Practice: EDI-SD-OCT is an exciting technology for imaging small choroidal lesions. It shows numerous changes in the overlying retina, especially shaggy photoreceptors, which can help differentiate small choroidal melanoma from similar-sized choroidal nevus. EDI-SD-OCT imaging is ideal only for smaller choroidal tumors (< 3 mm), particularly those located in the macula.
Relevance to Patients: EDI-SD-OCT is new imaging modality available for evaluating small choroidal lesions in the macula.
Stroke Rates After Introduction of Vascular Endothelial Growth Factor Inhibitors for Macular Degeneration: A Time Series Analysis
[published online ahead of print June 19, 2012]
Campbell RJ, Bell CM, Paterson JM, et al. Ophthalmol. 2012;119(8):1604-1608.
AMD treatment has been revolutionized by intravitreal anti-VEGF medications. Ranibizumab and bevacizumab are the commonly used drugs and have comparable efficacy. Intravenous administration of bevacizumab in patients with cancer has been associated with an increased risk of stroke, and a meta-analysis has suggested an increased risk of stroke among patients with AMD receiving ranibizumab.
The population-based, time series analysis was used to assess stroke rates among patients on therapy with bevacizumab and ranibizumab for AMD. The encrypted, linked health care databases in Ontario, Canada were used to select all patients aged 66 years or older with physician-diagnosed AMD in the previous 5 years between 2002 and 2010 (N = 116,388). A secondary analysis evaluated patients who had undergone photodynamic therapy (PDT) within the preceding year (N = 10,059).
A segmented regression analysis was used to evaluate changes in the rate of hospitalization for ischemic stroke associated with bevacizumab and ranibizumab therapy. The stroke rate was compared across 3 mutually exclusive periods: the period before the availability of bevacizumab or ranibizumab, the period of bevacizumab-dominant AMD therapy, and the period of ranibizumab-dominant AMD therapy. Neither the trend nor the level of the stroke time series changed with bevacizumab or ranibizumab therapy.
Similar results were observed in the analysis restricted to patients with recent PDT and in analyses stratified on age, sex, history of stroke, and history of diabetes. The present study was limited to strokes requiring hospitalization, and does not take into account milder vascular events not requiring hospitalization. Thus, use of intravitreal bevacizumab and ranibizumab for AMD is not associated with a change in the rate of hospitalization for stroke among Ontario seniors.
Application to Practice: The study results agree with the Comparisons of Age-Related Macular Degeneration Treatments (CATT) Trials regarding the safety of anti-VEGF agents. Stroke rates were not different in patients on bevacizumab and ranibizumab therapy. These results will assist clinicians as they balance the comparative efficacy, safety, and cost of these 2 closely related treatments.
Relevance to Patients: There is no difference in stroke rates in patients on bevacizumab and ranibizumab therapy.
Incidence of Endophthalmitis and Use of Antibiotic Prophylaxis After Intravitreal Injections
[published online ahead of print April 4, 2012]
Cheung CS, Wong AW, Lui A, Kertes PJ, Devenyi RG, Lam WC. Ophthalmol. 2012;119(8):1609-1614.
Intravitreal injections of VEGF inhibitors and triamcinolone acetonide are rapidly becoming the mainstay in treating various retinal diseases. A rare but sight-threatening complication of this procedure is endophthalmitis. The reported rates of endophthalmitis after intravitreal injections are low (0.019% to 1.4%). The preferred prophylactic method to minimize risk of endophthalmitis involves preparation of the injection site with topical povidone-iodine. There is conflicting evidence on the effectiveness of topical antibiotic prophylaxis in preventing endophthalmitis after intravitreal injections.
The retrospective, comparative case series studied the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-VEGF and triamcinolone acetonide. Three strategies of topical antibiotic prophylaxis were used by the treating physicians: antibiotics given for 5 days after each injection; antibiotics given immediately after each injection; and no antibiotics given. A total of 15,895 intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010.
Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics given immediately or for 5 days after injection showed lower rates of endophthalmitis compared with those without postinjection antibiotics. The incidence of endophthalmitis per injection was 2 in 935 for triamcinolone acetonide, 3 in 9453 for ranibizumab, and 4 in 5386 for bevacizumab. Thus, the overall rate of intravitreal injection-related endophthalmitis is greater with the use of topical antibiotics, given immediately or for 5 days after the injection, compared with no antibiotics.
Application to Practice: These findings recommend no topical antibiotic use after intravitreal injection, and they raise concern about a higher rate of endophthalmitis after administration of topical antibiotics. However, the study is retrospective, with a small sample of patients; hence, the conclusions may be the result of a random sampling error.
Relevance to Patients: The preparation of the intravitreal injection site with topical povidone-iodine is the preferred prophylactic method to minimize the risk of endophthalmitis. There is no need for topical antibiotic use after intravitreal injection.