Harry W. Flynn

A Variable-dosing Regimen with Intravitreal Ranibizumab for Neovascular Age-related Macular Degeneration: Year 2 of the PrONTO Study

PURPOSE To assess the long-term efficacy of a variable-dosing regimen with ranibizumab in the Prospective Optical Coherence Tomography (OCT) Imaging of Patients with Neovascular Age-Related Macular Degeneration (AMD) Treated with intraOcular Ranibizumab (PrONTO) Study, patients were followed for 2 years. DESIGN A 2-year prospective, uncontrolled, variable-dosing regimen with intravitreal ranibizumab based on OCT. METHODS In this open-label, prospective, single-center, uncontrolled clinical study, AMD patients with neovascularization involving the central fovea and a central retinal thickness (CRT) of at least 300 microm as measured by OCT were enrolled to receive 3 consecutive monthly intravitreal injections of ranibizumab (0.5 mg) [Lucentis; Genentech Inc, South San Francisco, California, USA]. During the first year, retreatment with ranibizumab was performed at each monthly visit if any criterion was fulfilled such as an increase in OCT-CRT of at least 100 microm or a loss of 5 letters or more. During the second year, the retreatment criteria were amended to include retreatment if any qualitative increase in the amount of fluid was detected using OCT. RESULTS Forty patients were enrolled and 37 completed the 2-year study. At month 24, the mean visual acuity (VA) improved by 11.1 letters (P < .001) and the OCT-CRT decreased by 212 microm (P < .001). VA improved by 15 letters or more in 43% of patients. These VA and OCT outcomes were achieved with an average of 9.9 injections over 24 months. CONCLUSIONS The PrONTO Study using an OCT-guided variable-dosing regimen with intravitreal ranibizumab resulted in VA outcomes comparable with the outcomes from the phase III clinical studies, but fewer intravitreal injections were required.

Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.

Purpose: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). Methods: A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. Results: Fifty–three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P<0.001) and the mean central retinal thickness decreased by 99.6 &mgr;m (P<0.001). Conclusion: Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.

Nosocomial Endophthalmitis Survey: Current Incidence of Infection after Intraocular Surgery

The authors reviewed the incidence of hospital-linked postoperative endophthalmitis at the Bascom Palmer Eye Institute between January 1, 1984 and June 30, 1989. After 30,002 intraocular surgical procedures, the following incidence of culture-proven endophthalmitis was observed: (1) extracapsular cataract extraction (ECCE) with or without intraocular lens (IOL) implantation--0.072% (17 of 23,625 cases); (2) pars plana vitrectomy--0.051% (1 of 1974 cases); (3) penetrating keratoplasty (PKP)--0.11% (2 of 1783 cases); (4) secondary IOL--0.30% (3 of 988 cases); and (5) glaucoma filtering surgery--0.061% (1 of 1632 cases). A statistically significant (P = 0.038, Fishers exact test, two-tailed) increased incidence of endophthalmitis occurred in diabetic (0.163%, 6 of 3686 cases) compared with nondiabetic (0.055%, 11 of 19,939 cases) patients undergoing ECCE with or without IOL implantation. The authors also reviewed the incidence of postoperative endophthalmitis after intracapsular cataract extraction (ICCE) with and without IOL and observed an incidence of 0.093% (7 of 7552) in cases operated on between September 1, 1976 and December 31, 1982.

Nosocomial acute-onset postoperative endophthalmitis survey: A 10-year review of incidence and outcomes

OBJECTIVE The purpose of the study was to evaluate the incidence of acute-onset (within 6 weeks after surgery) postoperative endophthalmitis and to assess the visual acuity outcomes after treatment over a 10-year period at one institution. PATIENTS AND METHODS This retrospective study reviews all surgical cases performed between January 1, 1984 and December 30, 1994 at the Anne Bates Leach Eye Hospital, Bascom Palmer Eye Institute, University of Miami Medical Center, for the occurrence of nosocomial acute-onset postoperative endophthalmitis. RESULTS The overall 10-year incidence of acute-onset postoperative endophthalmitis after intraocular surgery was 0.093% (54/58, 123). The incidences of culture-proven acute-onset postoperative endophthalmitis by surgical category were as follows: cataract surgery with or without intraocular lens (IOL) (0.082%, 34/41, 654), pars plana vitrectomy (PPV) (0.046%, 3/6557), penetrating keratoplasty (0.178%, 5/2805), secondary IOL placement (0.366%, 5/1367), glaucoma surgeries (0.124%, 4/3233), combined trabeculectomy and cataract surgery (0.114%, 2/1743), and combined penetrating keratoplasty and cataract surgery (0.194%, 1/515). The median visual acuity after endophthalmitis treatment was 20/200. The median visual acuities after endophthalmitis treatment by procedure were as follows: cataract surgery with or without IOL (20/133), PPV (no light perception), penetrating keratoplasty (2/200), secondary IOL implantation (20/40), glaucoma surgery (20/80), and combined trabeculectomy and cataract surgery with or without IOL (20/150). CONCLUSIONS The overall incidence of endophthalmitis after intraocular surgery was 0.093%. The incidence of endophthalmitis was higher after secondary IOL implantation than after cataract extraction (P = 0.008, Fishers exact test). After treatment, the visual acuity outcomes were worse in the patients who developed endophthalmitis after PPV than after cataract extraction, glaucoma procedures, or secondary IOL implantation (P < 0.05, analysis of variance, Duncans multiple range test). Acuity outcomes after treatment of endophthalmitis were better among the patients with secondary IOL implantation than after penetrating keratoplasty or PPV (P < 0.05, analysis of variance, Duncans multiple range test). The results of this 10-year review from a large teaching center may serve as a source of comparison for other centers and future studies.

Evolving guidelines for intravitreous injections.

Intravitreous (IVT) injection is increasingly being incorporated into the management of ocular diseases. While only fomivirsen sodium (Vitravene™) is currently approved by the Food and Drug Administration as an IVT injection, the number of approved IVT injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for IVT injection. The purpose of this document is to identify specific strategies for the delivery of IVT injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of IVT injection, additional clinical experience, and results of clinical trials.

Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane

PURPOSE To evaluate the surgical results in a series of patients with diabetic macular edema associated with traction from a thickened and taut posterior hyaloid membrane and to identify features associated with better visual outcome. METHODS We reviewed the clinical records of ten consecutive patients who underwent pars plana vitrectomy in one eye for diabetic macular edema that was preoperatively attributed to thickening and traction of the posterior hyaloid membrane. RESULTS Best-corrected, preoperative visual acuity was 20/200 in seven eyes, 20/300 in one eye, and 20/400 in two eyes. Intraoperatively, seven patients were found to have an attached posterior hyaloid membrane which was thickened and taut. Among these seven patients, postoperative best-corrected visual acuity improved by six lines in two eyes, by five lines in one eye, by two lines in one eye, and remained within one line of preoperative visual acuity in three eyes. The other three patients had an epiretinal membrane simulating an attached and thickened posterior hyaloid membrane. CONCLUSIONS Vitrectomy effectively improved visual acuity in some eyes with diabetic macular edema associated with traction from a thickened and taut posterior hyaloid membrane. Despite careful preoperative examination with a fundus contact lens, however, in some patients it may be difficult to assess how the posterior hyaloid membrane contributes to the macular edema. In selected patients, early surgical intervention may be associated with better visual outcome.

Endophthalmitis isolates and antibiotic sensitivities: a 6-year review of culture-proven cases

PURPOSE To investigate the spectrum of organisms causing culture-proven endophthalmitis and their susceptibilities to commonly used antimicrobial agents over 10 years. DESIGN Retrospective, noncomparative, consecutive case series. METHODS Medical records were reviewed of all cases with culture-proven endophthalmitis at a single institution from 2002 through 2011. The outcome measures included all intravitreal isolates identified as well as antibiotic susceptibilities. RESULTS A total of 448 organisms were isolated during the study interval. The most common organisms identified were Staphylococcus epidermidis in 30.1% (135/448), Streptococcus viridians group in 10.9% (49/448), Staphylococcus aureus in 7.8% (35/448), Candida albicans in 5.8% (26/443), other coagulase-negative staphylococci in 6.0% (27/448), Propionibacterium acnes in 4.7% (21/448), and Pseudomonas aeruginosa in 3.1% (14/448). Overall, 327 (72.9%) of 448 isolates were gram-positive organisms, 48 (10.7%) of 448 isolates were gram-negative organisms, 71 (15.8%) of 448 isolates were fungi, and 2 (0.4%) of 448 isolates were viruses. For gram-positive organisms, susceptibilities were the following: vancomycin, 100%; gentamicin, 88.0%; sulfamethoxazole/trimethoprim, 77.5%; levofloxacin, 58.5%; oxacillin, 54.7%; ciprofloxacin, 51.0%; gatifloxacin, 51.0%; and moxifloxacin, 47.0%. For gram-negative organisms, susceptibilities were the following: ceftazidime, 100%; levofloxacin, 100%; ciprofloxacin, 95.0%; tobramycin, 90.6%; gentamicin, 80.6%; and sulfamethoxazole/trimethoprim, 59.4%. CONCLUSIONS In the current study, no single antibiotic provided coverage for all of the microbes isolated from eyes with endophthalmitis. Combination therapy generally is the recommendation as the initial empiric treatment of suspected bacterial endophthalmitis. Appropriate history and characteristic clinical features may guide the use of initial antifungal agents.

Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy

Aims: The aim of this study was to report the development or progression of tractional retinal detachment (TRD) after the injection of intravitreal bevacizumab (Avastin) used as an adjuvant to vitrectomy for the management of severe proliferative diabetic retinopathy (PDR). Methods: The clinical charts of patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 mg bevacizumab before vitrectomy for the management of PDR were reviewed. Results: Eleven eyes (patients) out of 211 intravitreal injections (5.2%) that developed or had progression of TRD were identified. All eyes had PDR refractory to panretinal photocoagulation (PRP). Nine patients had type 1 diabetes mellitus (DM), and two patients had type 2 DM. Patients had a mean age of 39.5 years (range 22–62 years). In the current study, all patients used insulin administration and had poor glycaemic control (mean HbA1c 10.6%). Time from injection to TRD was a mean of 13 days (range 3–31 days). Mean best correct visual acuity (BCVA) at TRD development or progression was logarithm of the minimal angle of resolution (LogMAR) 2.2 (range 1.0–2.6) (mean Snellen equivalent hand motions; range 20/200 to light perception), a statistically significant worsening compared with baseline BCVA (p<0.0001). Eight eyes underwent vitrectomy and three patients refused or were unable to undergo surgery. The final mean BCVA after surgery was LogMAR 0.9 (range 0.2–2.0) (mean Snellen equivalent 20/160; range 20/32 to counting fingers), a statistically significant improvement compared with TRD BCVA (p = 0.002). Conclusions: TRD may occur or progress shortly following administration of intravitreal bevacizumab in patients with severe PDR.

Endophthalmitis After 25-gauge And 20-gauge Pars Plana Vitrectomy: Incidence and Outcomes

Purpose: To compare the rates of endophthalmitis after 20-gauge versus 25-gauge pars plana vitrectomy (PPV) and to investigate clinical features of, and visual acuity outcomes, for patients with endophthalmitis after PPV. Methods: A computerized database search was performed at each author’s institution to identify all patients who underwent PPV by any of the authors between January 1, 2005, and December 31, 2006, and were subsequently treated for endophthalmitis. In addition, all patients who underwent PPV and were subsequently treated for endophthalmitis at Pennsylvania State College of Medicine (Hershey, PA) and Bascom Palmer Eye Institute (Miami, FL) during the study period were included. The medical records of these patients were reviewed to confirm that the endophthalmitis was associated with PPV and to collect clinical data to meet the study objectives. Results: The incidence of endophthalmitis during the study period was 2 cases per 6,375 patients (or 1 case per 3,188 patients; 0.03%) for 20-gauge PPV compared with 11 cases per 1,307 patients (or 1 case per 119 patients; 0.84%) for 25-gauge PPV (P < 0.0001). Of 11 eyes that developed endophthalmitis after 25-gauge PPV, 9 received endophthalmitis prophylaxis with subconjunctival cefazolin after surgery. Median intraocular pressure on postoperative day 1 was 13 mmHg (range, 5–27 mmHg). Median time between PPV and endophthalmitis presentation was 3 days (range, 1–15 days). Presenting vision was hand motions or better in all eyes. Initial treatment included vitreous tap and injection of antibiotics in nine eyes and PPV and injection of antibiotics in two. All patients received intraocular treatment with vancomycin, and 10 received ceftazidime treatment. Eight patients had final visual acuity of ≥20/400, and four had visual acuity of ≥20/63. Cultures were negative in three cases; no culture specimens were obtained in one case. Six of the seven isolates were coagulase-negative staphylococci, and one was enterococcus. Five of six isolates tested for sensitivity to vancomycin were sensitive, and both isolates tested for sensitivity to ceftazidime were sensitive. Conclusions: The rate of endophthalmitis after 25-gauge PPV was significantly higher than that after 20-gauge PPV. Endophthalmitis after 25-gauge PPV occurred within 15 days of PPV, was usually due to coagulase-negative staphylococci sensitive to vancomycin, and was associated with variable visual outcomes.

Silicone oil in the repair of complex retinal detachments. A prospective observational multicenter study.

OBJECTIVE This study aimed to report anatomic and visual acuity outcomes and complications after 1000-centistoke silicone oil was used as a retinal tamponade for the treatment of complex retinal detachments. DESIGN Prospective observational multicenter study conducted at community and university-based ophthalmology clinics. PARTICIPANTS The study cohort consisted of 2439 patients (2573 eyes) treated for complex retinal detachments associated with cytomegalovirus (CMV) necrotizing retinitis or a non-CMV etiology, including proliferative diabetic retinopathy, giant retinal tears, proliferative vitreoretinopathy, or ocular trauma. INTERVENTION Vitrectomy surgery was performed for complex retinal detachment with 1000-centistoke silicone oil as the retinal tamponade. MAIN OUTCOME MEASURES Anatomic outcomes were complete retinal attachment and macular attachment. Visual acuity outcomes were ambulatory vision (> or = 4/200) and preservation of preoperative visual acuity. Complications were rates of secondary intraocular pressure elevation (> or = 30 mmHg), hypotony (< or = 5 mmHg), corneal opacification (including band keratopathy, corneal edema, and corneal abrasions), oil emulsification, and cataract. Outcomes were assessed 6, 12, and 24 months after surgery. RESULTS At the 6-month examination, the retina was completely attached in 178 (78%) of 228 CMV eyes and in 855 (70%) of 1219 non-CMV eyes. The macula was attached in 216 (95%) of 228 and 1062 (89%) of 1189 CMV and non-CMV eyes, respectively. Ambulatory vision was noted in 151 (65%) of 234 CMV eyes and in 480 (38%) of 1251 non-CMV eyes. Visual acuity was preserved in 106 (46%) of 230 and 1035 (84%) of 1229 CMV and non-CMV eyes, respectively. The corresponding rates of complications for CMV and non-CMV eyes were: elevated intraocular pressure, 0 (0%) of 196 and 35 (3%) of 1196; hypotony, 11 (6%) of 196 and 228 (19%) of 1196; corneal opacity, 13 (6%) of 229 and 326 (26%) of 1248; emulsification, 3 (1%) of 211 and 29 (3%) of 959; and cataract in phakic eyes, 118 (64%) of 185 and 50 (63%) of 80. CONCLUSIONS Retinal reattachment was achieved in the majority of eyes using vitrectomy and silicone oil retinal tamponade. Complication rates generally were less frequent in CMV eyes, but follow-up was shorter in this group of patients, largely because of reduced life expectancy. Cataract frequently developed in phakic eyes of study patients. Use of 1000-centistoke silicone oil can be considered in the management of complex retinal detachments associated with multiple etiologies.