Mary K. Daly

Bevacizumab vs Ranibizumab for Age-Related Macular Degeneration: Early Results of a Prospective Double-Masked, Randomized Clinical Trial

PURPOSE To report early outcomes of a prospective, double-masked, controlled trial comparing bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) to ranibizumab (Lucentis; Genentech Inc) for the treatment of age-related macular degeneration. DESIGN Prospective, double-masked, randomized clinical trial. METHODS This is a single-center, randomized clinical trial at the Boston Veterans Affairs Healthcare System. Patients who met inclusion criteria were randomized 2:1 to bevacizumab or ranibizumab. Each patient contributed 1 eye to the study. All subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Visual acuity (VA) was checked on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by optical coherence tomography-guided, variable-dosing schedule. Main outcomes measured were VA and foveal thickness. RESULTS Twenty patients completed the 6-month follow up. Thirteen patients received bevacizumab and 7 patients received ranibizumab. No subjects in either group lost more than 15 letters on ETDRS chart. The average preoperative VA was 31.6 letters in the bevacizumab group and 30.4 letters in the ranibizumab group. At 6 months follow-up, mean vision was 46.4 letters in the bevacizumab group and 37.4 letters in the ranibizumab group. Two-tailed ttest failed to show statistical significance between the two groups. Patients in the bevacizumab group underwent an average of 5 injections, while patients in the ranibizumab group underwent a mean of 4 injections. CONCLUSION Early results of a head-to-head, randomized, double-masked, prospective, single-center controlled trial between bevacizumab and ranibizumab show no difference in efficacy between the two treatments for choroidal neovascularizaton in the treatment of age-related macular degeneration. As this study conveys results of a small number of patients, further studies with larger sample sizes are needed in order to establish statistical significance.

Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomised clinical trial

PurposeTo report 1-year visual and anatomic outcomes of a prospective, double-masked randomised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration (AMD).MethodsPatients who met inclusion criteria were randomised 2 : 1 to bevacizumab or ranibizumab. All subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Visual acuity was taken on Early Treatment Diabetic Retinopathy Study chart. Patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by an optical coherence tomography-guided, variable-dosing treatment schedule. Main outcomes measured included visual acuity, foveal thickness, and total number of injections over the 1-year treatment period.ResultsIn total, 15 patients received bevacizumab and 7 patients received ranibizumab. The average pre-operative visual acuity was 34.9 letters in the bevacizumab group, and 32.7 letters in the ranibizumab group. At 1-year follow-up, mean vision was 42.5 letters in the bevacizumab group, and 39.0 letters in the ranibizumab group. Two-tailed t-test failed to showed statistical significance between the two groups (P=0.5). Patients in the bevacizumab group underwent an average of eight injections, whereas patients in the ranibizumab group underwent a mean of four injections (P=0.001).ConclusionThe 1-year outcomes of a prospective, double-masked, randomised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD. Total injections given over the treatment period were significantly different between the two groups. Further studies with larger sample sizes are warranted.

Informed consent for cataract surgery: Patient understanding of verbal, written, and videotaped information

PURPOSE: To determine the effectiveness of verbal, written, and videotaped descriptions of cataract surgery on patients’ understanding of the risks, benefits, and treatment alternatives. SETTING: Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. DESIGN: Randomized prospective study. METHODS: Patients eligible for cataract surgery were randomized into 1 of 4 arms of the informed consent process as follows: Group 1, conventional verbal information; Group 2, conventional verbal information plus second‐grade reading level brochure; Group 3, conventional verbal information plus eighth‐grade reading level brochure; Group 4, conventional verbal information plus American Academy of Ophthalmology DVD Understanding Cataract Surgery: Patient Education DVD Featuring an Aid to Informed Consent. After the informed consent process, patients in each group completed a 12‐question questionnaire discussing the surgical procedure, its benefits, its foreseeable and unforeseeable risks, and the alternatives to cataract surgery. Scores in each group were calculated as the number of correct responses out of 12 questions. RESULTS: Patients in Group 2 (mean score 10.8 ± 1.29 [SD]) and Group 4 (mean score 10.56 ± 1.44) scored significantly higher than patients in Group 1 (mean score 7.68 ± 2.80) or Group 3 (mean score 9.08 ± 1.60). Previous cataract surgery and education level had no significant influence on recall of the informed‐consent process. CONCLUSIONS: Concise informed consent information sheets at lower reading grade levels and videotape presentation optimized patient understanding of the risks, benefits, and treatment alternatives to cataract surgery. The cost–benefit of these results is important because better patient understanding has the potential to decrease the risk for indemnity payments awarded because of inadequate informed consent. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Evolution of treatment strategies for adenocarcinoma of the esophagus and gastroesophageal junction

Between 1980 and 1988, 91 patients with adenocarcinoma of the esophagus were treated by surgical resection and selective postoperative therapy. Operative mortality was 2%. Pathologic stage was I in 4, II in 26, and III in 61. Actuarial 2- and 5-year survival was 24% and 8%. From 1987 to 1989, 16 patients with adenocarcinoma of the esophagus were treated with two cycles of 5-fluorouracil and cisplatin followed by surgical resection. There was 1 complete response (6%), 5 partial responses (31%), and 10 with no response (63%). Twelve patients had resection. Pathologic stage was I in 1, II in 4, and III in 8. There was one chemotherapy-related death and one surgical death. Actuarial 4-year survival is 42%. From 1990 to 1993, 22 patients with adenocarcinoma of the esophagus were treated with two cycles of etoposide, doxorubicin, and cisplatin followed by surgical resection. There was 1 complete response (5%), 11 partial responses (50%), and 10 with no response (45%). Eighteen patients had resection. Pathologic stage was 0 in 1, II in 8, and III in 9. There were no treatment-related deaths. The actuarial 2-year survival is 58%. Conclusions are necessarily limited because the patients were not treated in a randomized fashion. These preliminary results with preoperative chemotherapy appear improved (p = 0.04 and p = 0.004, respectively) as compared with results from 1980 to 1988 without preoperative chemotherapy.

Management of mydriasis and pain in cataract and intraocular lens surgery: review of current medications and future directions

The maintenance of mydriasis and the control of postoperative pain and inflammation are critical to the safety and success of cataract and intraocular lens replacement surgery. Appropriate mydriasis is usually achieved by topical and/or intracameral administration of anticholinergic agents, sympathomimetic agents, or both, with the most commonly used being cyclopentolate, tropicamide, and phenylephrine. Ocular inflammation is common after cataract surgery. Topical steroids and nonsteroidal anti-inflammatory drugs are widely used because they have been proved effective to control postsurgical inflammation and decrease pain. Topical nonsteroidal anti-inflammatory drugs have also been shown to help maintain dilation. However, use of multiple preoperative drops for pupil dilation, inflammation, and pain control have been shown to be time consuming, resulting in delays to the operating room, and they cause dissatisfaction among perioperative personnel; their use can also be associated with systemic side effects. Therefore, ophthalmologists have been in search of new options to streamline this process. This article will review the current medications commonly used for intraoperative mydriasis, as well as pain and inflammation control. In addition, a new combination of ketorolac, an anti-inflammatory agent, and phenylephrine, a mydriatic agent has recently been designed to maintain intraoperative mydriasis and to reduce postoperative pain and irritation from intraocular lens replacement surgery. Two Phase III clinical trials evaluating this combination have demonstrated statistically significant differences when compared to placebo in maintaining intraoperative mydriasis (P<0.00001) and in reducing pain in the early postoperative period (P=0.0002). This medication may be of benefit for use in cataract and lens replacement surgery in the near future.

Efficacy of surgical simulator training versus traditional wet-lab training on operating room performance of ophthalmology residents during the capsulorhexis in cataract surgery

Purpose To compare the operating room performance of ophthalmology residents trained by traditional wet‐lab versus surgical simulation on the continuous curvilinear capsulorhexis (CCC) portion of cataract surgery. Setting Academic tertiary referral center. Design Prospective randomized study. Methods Residents who chose to participate and provided informed consent were randomized to preoperative CCC training in the wet lab or on a simulator. Residents completed pre‐practice demographic questionnaires including habits of daily living. After completion of their preoperative training (wet lab versus simulator), residents performed their first CCC of the clinical rotation under the direct supervision of an attending physician as part of their standard training at the facility. Residents then completed satisfaction questionnaires regarding their preoperative training. Two attending surgeons reviewed and graded each video of operating room performance. The mean score between the 2 attending physicians was used as the individual performance score for each of the 12 performance criteria. The overall score was calculated as the sum of these 12 individual performance scores (standardized). Results Ten residents trained in the wet lab and 11 on the simulator. There was no significant difference in overall score between the 2 groups (P=.608). There was no significant difference in any individual score except time (wet‐lab group faster than simulator group) (P=.038). Conclusions Preoperative simulator training prepared residents for the operating room as effectively as the wet lab. The time to pass the simulator curriculum was predictive of the time and overall performance in the operating room. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Intraoperative Floppy Iris and Prevalence of Intraoperative Complications: Results From Ophthalmic Surgery Outcomes Database

PURPOSE To estimate the prevalence of untoward events during cataract surgery with the use of pupillary expansion devices and intraoperative floppy iris (IFIS). DESIGN Retrospective analysis of 4923 cataract surgery cases from the Veterans Affairs Ophthalmic Surgical Outcomes Data Project. METHODS Outcomes from 5 Veterans Affairs medical centers were analyzed, including use of alpha-blockers (both selective and nonselective), IFIS, intraoperative iris trauma, intraoperative iris prolapse, posterior capsular tear, anterior capsule tear, intraoperative vitreous prolapse, and use of pupillary expansion devices. P values were calculated using the χ(2) test. RESULTS A total of 1254 patients (25.5%) took alpha-blockers preoperatively (selective, 587; nonselective, 627; both, 40). Of these 1254 patients, 428 patients (34.1%) had documented IFIS. However, 75.2% of patients with IFIS (428/569) had taken alpha-blockers preoperatively (P < .00001). A total of 430 patients (8.7%) had a pupillary expansion device used during their cataract surgery, of which 186 patients (43.4%) had IFIS (P < .0001). Eighty-six patients with IFIS had at least 1 intraoperative complication and 39 patients with IFIS had more than 1 intraoperative complication (P < .001). CONCLUSIONS The use of either selective or nonselective alpha-antagonists preoperatively demonstrated a significant risk of IFIS. Nonselective alpha-antagonists caused IFIS at a higher prevalence than previously reported. This study did demonstrate statistically significant increased odds of surgical complications in patients with IFIS vs those without IFIS in all groups (those taking selective and nonselective alpha-antagonists and also those not taking medications).

Effect of trypan blue staining on the elastic modulus of anterior lens capsules of diabetic and nondiabetic patients

PURPOSE: To determine whether trypan blue causes a significant difference in the biomechanical properties (stiffness) of diabetic and nondiabetic anterior lens capsules and to determine whether diabetes significantly alters the stiffness of anterior lens capsules. SETTING: Veterans Administration Boston Healthcare Center System, Jamaica Plain, Massachusetts, USA. METHODS: In this unmasked prospective randomized controlled experimental study, anterior lens capsules were obtained from diabetic and nondiabetic patients approved for cataract surgery. Four treatment groups were created: (1) capsules of nondiabetic patients without trypan blue; capsules of nondiabetic patients with trypan blue; (3) capsules of diabetic patients without trypan blue; (4) capsules of diabetic patients with trypan blue. Anterior lens capsule stiffness as a function of elastic (Youngs) modulus (kilopascals) was measured with the Hysitron TriboIndenter. RESULTS: The use of trypan blue led to significantly stiffer anterior lens capsules (P = .036). Trypan blue had the greatest effect on the stiffness of diabetic lens capsules (P = .046). CONCLUSION: Trypan blue contributed to increased capsule stiffness during capsulorhexis, especially in diabetic patients.

Outcomes of cataract surgery with residents as primary surgeons in the Veterans Affairs Healthcare System.

Purpose To explore visual outcomes, functional visual improvement, and events in resident‐operated cataract surgery cases. Setting Veterans Affairs Ophthalmic Surgery Outcomes Database Project across 5 Veterans Affairs Medical Centers. Design Retrospective data analysis of deidentified data. Methods Cataract surgery cases with residents as primary surgeons were analyzed for logMAR corrected distance visual acuity (CDVA) and vision‐related quality of life (VRQL) measured by the modified National Eye Institute Vision Function Questionnaire and 30 intraoperative and postoperative events. In some analyses, cases without events (Group A) were compared with cases with events (Group B). Results The study included 4221 cataract surgery cases. Preoperative to postoperative CDVA improved significantly in both groups (P < .0001), although the level of improvement was less in Group B (P = .03). A CDVA of 20/40 or better was achieved in 96.64% in Group A and 88.25% in Group B (P < .0001); however, Group B had a higher prevalence of preoperative ocular comorbidities (P < .0001). Cases with 1 or more events were associated with a higher likelihood of a postoperative CDVA worse than 20/40 (odds ratio, 3.82; 95% confidence interval, 2.92‐5.05; P < .0001) than those who did not experience an event. Both groups had a significant increase in VRQL from preoperative levels (both P < .0001); however, the level of preoperative to postoperative VRQL improvement was significantly less in Group B (P < .0001). Conclusion Resident‐operated cases with and without events had an overall significant improvement in visual acuity and visual function compared with preoperatively, although this improvement was less marked in those that had an event. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

Effects of tear gases on the eye

Chemical agents that target the eyes have been a popular choice for law enforcement during riots and for military training for nearly a century. The most commonly used agents are chloroacetophenone (formerly sold as Mace), o-chlorobenzylidene malononitrile, and oleoresin capsicum (OC or pepper spray, current ingredient for Mace). Initially, most severe ocular injuries were caused by the explosive force rather than the chemical itself. The development of sprays reduced the mechanical severity of ocular injuries, but resulted in a variety of chemical injuries. The effects on eyes include conjunctival injection, complete corneal epithelial defects, pseudopterygium, corneal neovascularization, persistent conjunctivalization, corneal opacities, and reduced visual acuity. Current management, based on limited human studies, emphasizes decontamination and symptomatic treatment. We review the literature related to clinical and histopathologic effects of tear gas agents on the eye and their management.