PATIENT-REPORTED VISUAL FUNCTION FROM THE OCRIPLASMIN FOR TREATMENT FOR SYMPTOMATIC VITREOMACULAR ADHESION, INCLUDING MACULAR HOLE (OASIS) STUDY.

PURPOSE: To evaluate patient-reported visual function after ocriplasmin through the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) in patients with symptomatic vitreomacular adhesion/vitreomacular traction including macular hole. METHODS: This was a prespecified analysis of a secondary endpoint from the OASIS trial. Patients received a single intravitreal injection of ocriplasmin (0.125 mg) or sham and completed the VFQ-25 questionnaire at baseline and at Months 6, 12, and 24. Clinically meaningful (≥5-point) changes from baseline were assessed. RESULTS: Of the 220 patients enrolled, 146 received ocriplasmin and 74 received sham. At Month 24, the percentage of patients with a ≥5-point improvement from baseline in VFQ-25 composite scores was higher with ocriplasmin versus sham (51.4% vs. 30.1%, 95% confidence interval, 8.1-34.5, P = 0.003). The percentage of patients with ≥5-point worsening at Month 24 was lower with ocriplasmin versus sham (9.5% vs. 15.6%, 95% confidence interval: -15.6 to 3.5, P = 0.191). A larger percentage of patients treated with ocriplasmin versus sham experienced a ≥5-point improvement in VFQ-25 composite and subscale scores at Month 24 regardless of baseline full-thickness macular hole status. CONCLUSION: A larger percentage of patients with symptomatic vitreomacular adhesion/vitreomacular traction reported clinically meaningful improvements in self-assessed visual function with ocriplasmin than sham.

Results of the 2-Year Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) Randomized Trial.

PURPOSE: The Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial was designed to evaluate the long-term efficacy and safety profile of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA)/vitreomacular traction, including full-thickness macular hole (FTMH). DESIGN: Phase 3b, randomized, sham-controlled, double-masked, multicenter clinical trial. PARTICIPANTS: Sample size was 220 subjects (146 ocriplasmin, 74 sham) randomized in a 2:1 ratio to receive intravitreal ocriplasmin 0.125 mg or sham injection. METHODS: The trial involved 12 visits over 24-months. Inclusion criteria included presence of VMA and best-corrected visual acuity (BCVA) of 20/32 or worse in the study eye. Exclusion criteria included FTMH >400 µm, presence of epiretinal membrane (ERM), and aphakia in the study eye. MAIN OUTCOME MEASURES: The primary efficacy end point was the proportion of subjects with pharmacologic VMA resolution at day 28. Secondary efficacy end points were assessed at month 24 and included proportion of subjects with BCVA gain from baseline, nonsurgical FTMH closure, vitrectomy, and Visual Function Questionnaire 25 (VFQ-25) outcomes. RESULTS: The OASIS trial met its primary end point with pharmacologic VMA resolution at day 28 being significantly higher in the ocriplasmin group (41.7%) compared with the sham group (6.2%). The treatment effect was maintained until study end. In the ocriplasmin group, pharmacologic VMA resolution at day 28 was higher in subgroups with the following baseline characteristics compared with the complementary subgroups without them: presence of focal VMA, presence of FTMH, absence of ERM, and phakic lens status. In the ocriplasmin group, 50.5% of subjects had a ≥2-line improvement in BCVA from baseline compared with 39.1% of subjects in the sham group. The nonsurgical FTMH closure rate was 30.0% for the ocriplasmin group compared with 15.4% for the sham group. All other secondary end points also favored ocriplasmin over sham. Regarding safety, most adverse events were mild to moderate, had a short onset time, and were transient, with no new safety signals identified. CONCLUSIONS: The OASIS trial demonstrates the long-term efficacy and safety of ocriplasmin, providing improved resolution of symptomatic VMA compared with previous phase 3 trials with no additional safety signals identified.

One-year outcomes of eyes treated with a sutureless scleral fixation technique for intraocular lens placement or rescue.

PURPOSE: To report the 1 year results of a novel surgical technique for sutureless scleral fixation of a 3-piece intraocular lens. METHODS: Retrospective consecutive series of patients who underwent sutureless scleral fixation of a three-piece intraocular lens. All patients were required to have at least 1 year of follow-up to be included in the series. Outcomes data were obtained and treated with simple statistical analyses. RESULTS: A total of 24 patients were included in the study population. The average age was 75 years (range, 44-87). Short-term complications were few and included vitreous hemorrhage (n = 2), elevated intraocular pressure (n = 1), and hypotony (n = 1). Long-term complications included intraocular lens dislocation (n = 3) and cystoid macular edema (n = 1). Mean visual acuity improved from logMAR 1.30 (Snellen 20/399) to 0.52 (Snellen 20/66) at 1 year. CONCLUSION: This novel technique for sutureless scleral fixation of a three-piece intraocular lens was well-tolerated 1 year after surgery.

Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study.

OBJECTIVE: To determine long-term outcomes of patients with ranibizumab-treated retinal vein occlusion (RVO). DESIGN: Prospective follow-up of a subset of patients from 2 phase 3 trials. PARTICIPANTS: Thirty-four patients with branch RVO (BRVO) and 32 with central RVO (CRVO) who completed the Genentech-sponsored ranibizumab study RVO trials. METHODS: Patients seen every month in year 1 and at least every 3 months in year 2 were treated with ranibizumab for intraretinal fluid. Patients requiring injections on consecutive visits were treated with ranibizumab plus scatter photocoagulation. MAIN OUTCOME MEASURES: Mean improvement in best-corrected visual acuity (BCVA) and percentage of patients with edema resolution. RESULTS: With a mean follow-up of 49.0 months, 17 of 34 BRVO patients (50%) had edema resolution defined as no intraretinal fluid for 6 months or more after the last injection. The last injection was given within 2 years of treatment initiation in 76%. The mean number of injections required in unresolved patients in year 4 was 3.2. In patients with resolved edema mean improvement in BCVA was 25.9 letters versus 17.1 letters (P = 0.09) in unresolved patients, and in both groups, approximately 80% had a final BCVA of 20/40 or better. With a mean follow-up of 49.7 months, 14 of 32 CRVO patients (44%) had edema resolution, with 71% receiving their last injection within 2 years of treatment initiation. The mean number of injections in unresolved patients in year 4 was 5.9. Compared with patients with unresolved CRVO, patients with resolved disease had greater improvement in BCVA (25.2 vs. 4.3 letters; P = 0.002), and a greater percentage had a final BCVA of 20/40 or better (64.3% vs. 27.8%; P = 0.04). Nine patients with BRVO and 9 with CRVO received scatter photocoagulation, and with mean follow-up of 9 months (BRVO) and 11 months (CRVO) after last laser, only 1 in each group had resolution of edema. CONCLUSIONS: Long-term outcomes in BRVO patients treated with ranibizumab were excellent, and although half still required occasional injections after 4 years, they maintained good visual potential. A substantial minority (44%) of patients with ranibizumab-treated CRVO had edema resolution and a good outcome within 4 years, but most (56%) still required frequent injections, had reduced visual potential, and have a guarded prognosis.

Aqueous levels of fluocinolone acetonide after administration of fluocinolone acetonide inserts or fluocinolone acetonide implants.

PURPOSE: To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY). DESIGN: Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials. PARTICIPANTS: Thirty-seven patients with diabetic macular edema (DME) (Fluocinolone Acetonide in Human Aqueous [FAMOUS] Study, C-01-06-002) and 7 patients with uveitis (NA-00019318). METHODS: Aqueous FAc was measured after administration of FAc implants or 0.2 µg/day (low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 µg/day (high dose) FAc inserts. MAIN OUTCOME MEASURES: The primary end point was aqueous levels of FAc. RESULTS: At 1 month after administration for subjects who received 1 treatment, mean aqueous FAc levels were 2.17 (low dose) and 3.03 ng/ml (high dose) for FAc inserts and 6.12 ng/ml for FAc implants with maximum levels of 3.83, 6.66, and 13.50 ng/ml, respectively. At 3 months, mean FAc levels were 1.76, 2.15, and 6.12 ng/ml, respectively. Between 6 and 36 months after low-dose inserts, aqueous levels of FAc were remarkably stable, ranging from 1.18 to 0.45 ng/ml. After high-dose inserts, mean FAc levels were stable between 6 and 24 months, ranging from 1.50 to 0.84 ng/ml and then decreasing to 0.35 ng/ml at 30 months and 0.15 ng/ml at 36 months. In implant-containing eyes, mean FAc levels remained >6 ng/ml through 15 months, the last time point with measurements from at least 6 eyes. CONCLUSIONS: Low- and high-dose FAc inserts both provide stable long-term release of FAc with comparable peak levels in the aqueous: slightly >2 ng/ml for approximately 3 months followed by steady-state levels between 1.0 and 0.5 ng/ml through 36 months for low-dose inserts versus levels between 1.5 and 1.1 ng/ml through 24 months for high-dose inserts. Steady-state aqueous levels after FAc implants were >6 ng/ml. These results provide new insights that aid in the interpretation of efficacy trials and indicate that there is a dose effect for steroid-induced ocular hypertension. In susceptible patients, prolonged aqueous levels of FAc >1 ng/ml moderately increased the risk of glaucoma and levels >6 ng/ml posed a markedly increase risk.

Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE.

PURPOSE: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME). DESIGN: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years. PARTICIPANTS: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 µm on optical coherence tomography. METHODS: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary. MAIN OUTCOME MEASURES: The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24. RESULTS: Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group. CONCLUSIONS: The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE.

PURPOSE: To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients. DESIGN: Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies. PARTICIPANTS: Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 µm on time-domain optical coherence tomography (OCT). INTERVENTION: Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol-specified criteria. MAIN OUTCOME MEASURES: Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months. RESULTS: In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P<0.0001; difference vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8-34.8) and 39.2% of 0.5-mg ranibizumab patients (P<0.001; adjusted difference, 20.9%; 95% CI, 10.7-31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients versus 33.6% of 0.3-mg patients (P<0.0001; adjusted difference, 20.8%; 95% CI, 11.4-30.2) and 45.7% of 0.5-mg ranibizumab patients (P<0.0001; adjusted difference, 33.3%; 95% CI, 23.8-42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients. Ranibizumab-treated patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3-0.8 in ranibizumab groups). Ocular safety was consistent with prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to 8.8% of ranibizumab patients. CONCLUSIONS: Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm.

Incidence of retinal pigment epithelial tears after intravitreal ranibizumab injection for neovascular age-related macular degeneration.

OBJECTIVE: To explore the association between treatment for neovascular age-related macular degeneration (AMD) and incidence and timing of retinal pigment epithelium (RPE) tears in ranibizumab-treated patients versus control treatment. DESIGN: Results from 3 phase III clinical trials (ANti-VEGF antibody for the treatment of predominantly classic CHORoidal neovascularization in age-related macular degeneration [ANCHOR], Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular Age-related macular degeneration [MARINA], and A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization [CNV] with or without Classic CNV Secondary to Age-Related Macular Degeneration [PIER]) were retrospectively reviewed to identify patients who developed RPE tears during the study period, detected on fluorescein angiography performed at prespecified intervals. PARTICIPANTS: Patients with baseline and post-baseline angiographic assessments. METHODS: Patients received intravitreal ranibizumab (0.3 or 0.5 mg) or control treatment (verteporfin photodynamic therapy [PDT] in ANCHOR and sham intravitreal injections in ANCHOR, MARINA, and PIER). MAIN OUTCOME MEASURES: Incidence and timing of RPE tears during the treatment period. RESULTS: Data from 1298 patients were analyzed. No statistically significant differences in RPE tear incidence were observed. The pooled rate of RPE tears was 1.8% with 0.5 mg ranibizumab, 3.0% with 0.3 mg ranibizumab, and 1.6% in the control group. Most (76%; 16/21) RPE tears in ranibizumab-treated patients were identified within 3 months of initiating treatment, whereas the majority (80%; 4/5) of late-onset RPE tears occurred in control patients. In patients who developed RPE tears, better visual acuity (VA) outcomes were observed in those treated with ranibizumab versus control treatment. CONCLUSIONS: As studied in these trials, no statistically significant differences in the incidence of RPE tears within a 2-year treatment period were observed in patients who received ranibizumab (0.5 or 0.3 mg) versus control treatment, although most RPE tears with ranibizumab occurred within 3 months of initiating treatment. Mean VA was better in patients who developed RPE tears while receiving ranibizumab than in those who received control treatment, suggesting a potential benefit of continued ranibizumab therapy in patients with neovascular AMD who developed RPE tears. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study.

PURPOSE: To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion (BRVO). DESIGN: Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial. PARTICIPANTS: A total of 397 patients with macular edema following BRVO. METHODS: Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. MAIN OUTCOME MEASURES: The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT). RESULTS: Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 16.6 (14.7-18.5) and 18.3 (16.0-20.6) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 (5.1-9.5) in the sham group (P<0.0001 for each ranibizumab group vs sham). The percentage of patients who gained > or =15 letters in BCVA at month 6 was 55.2% (0.3 mg) and 61.1% (0.5 mg) in the ranibizumab groups and 28.8% in the sham group (P<0.0001 for each ranibizumab group vs sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg, 67.9%; 0.5 mg, 64.9%) had BCVA of > or =20/40 compared with sham patients (41.7%; P<0.0001 for each ranibizumab group vs sham); and CFT had decreased by a mean of 337 microm (0.3 mg) and 345 microm (0.5 mg) in the ranibizumab groups and 158 microm in the sham group (P<0.0001 for each ranibizumab group vs sham). The median percent reduction in excess foveal thickness at month 6 was 97.0% and 97.6% in 0.3 mg and 0.5 mg groups and 27.9% in the sham group. More patients in the sham group (54.5%) received rescue grid laser compared with the 0.3 mg (18.7%) and 0.5 mg (19.8%) ranibizumab groups. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with BRVO. CONCLUSIONS: Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid, effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events.

Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert.

PURPOSE: To compare Iluvien intravitreal inserts that release 0.2 or 0.5 microg/day of fluocinolone acetonide (FA) in patients with diabetic macular edema (DME). DESIGN: Prospective, randomized, interventional, multicenter clinical trial. PARTICIPANTS: We included 37 patients with DME. METHODS: Subjects with persistent DME despite > or = 1 focal/grid laser therapy were randomized 1:1 to receive an intravitreal insertion of a 0.2- or a 0.5-microg/day insert. MAIN OUTCOME MEASURES: The primary end point was aqueous levels of FA throughout the study with an important secondary outcome of the change from baseline in best-corrected visual acuity (BCVA) at month 12. RESULTS: The mean aqueous level of FA peaked at 3.8 ng/ml at 1 week and 1 month after administration of a 0.5-microg/day insert and was 3.4 and 2.7 ng/ml 1 week and 1 month after administration of a 0.2-microg/day insert. For both inserts, FA levels decreased slowly thereafter and were approximately 1.5 ng/ml for each at month 12. The mean change from baseline in BCVA was 7.5, 6.9, and 5.7 letters at months 3, 6, and 12, respectively, after administration of a 0.5 microg/day-insert and was 5.1, 2.7, and 1.3 letters at months 3, 6, and 12, respectively, after administration of a 0.2-microg/day insert. There was a mild increase in mean intraocular pressure after administration of 0.5-microg/day inserts, but not after administration of 0.2-microg/day inserts. CONCLUSIONS: The FA intravitreal inserts provide excellent sustained intraocular release of FA for > or = 1 year. Although the number of patients in this trial was small, the data suggest that the inserts provide reduction of edema and improvement in BCVA in patients with DME with mild effects on intraocular pressure over the span of 1 year. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Short-term effectiveness of intravitreal bevacizumab versus ranibizumab injections for patients with neovascular age-related macular degeneration.

PURPOSE: To compare the effectiveness of three consecutive intravitreal injections of bevacizumab (Avastin) and ranibizumab (Lucentis) in patients with treatment-naïve neovascular age-related macular degeneration. METHODS: This is a retrospective comparative study of qualifying consecutively treated patients (n = 176) with new-onset subfoveal choroidal neovascularization presenting at 6 retina referral centers. Patients were treated with 3 consecutive monthly injections of ranibizumab (0.5 mg) or 3 injections of bevacizumab every 6 weeks (1.25 mg) as determined by physician and patient preference. Ophthalmologic evaluations included monthly visual acuity measurements, ocular examinations, and optical coherence tomography imaging at each visit. RESULTS: A 29.2% reduction in the mean central foveal thickness measurement through optical coherence tomography was found in the ranibizumab-treated patients versus a 20.9% reduction in the bevacizumab-treated patients (P

Variability in Optical Coherence Tomography Angiography Interpretation in a Cohort of Retina Specialists.

BACKGROUND AND OBJECTIVE: To investigate the variability in optical coherence tomography angiography (OCTA) image interpretation in a cohort of retina specialists. PATIENTS AND METHODS: A survey consisting of a study set of images from 12 eyes examined by OCTA was created. Eight multiple-choice answers were provided as response options for each case. The survey was sent to 100 retina specialists, with instructions to complete the survey only if they had facility with the interpretation of OCTA images. Thirty-eight physicians completed the survey. Data generated were subsequently analyzed and interpreted. RESULTS: Krippendorff's alpha coefficients of agreement and their associated 95% confidence intervals (CIs) were utilized for statistical analyses. For the overall data, the estimated alpha coefficient was 0.366 (95% CI, 0.31-0.47). Although the estimated alpha coefficient is significant, the level of significance is considered low, as it is far from unity (0.366). Therefore, although statistically significant, the overall data did not demonstrate either high reliability or agreement in interpretation. Additional analyses evaluating the influence of years and location of practice, and frequency of OCTA use did not demonstrate a significant effect on reliability measures. CONCLUSIONS: Significant variability exists in the interpretation of OCTA images in this cohort of retina specialists. The overall data did not demonstrate high reliability or agreement in interpretation of images, suggesting the need for additional study of this nascent technology. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:344-353.].

UNILATERAL BEST DISEASE: A CASE REPORT.

PURPOSE: To describe the multimodal imaging findings observed unilaterally in a patient with Best disease due to a p.G15D mutation in the BEST1 gene. METHODS: The clinical history of a 62-year-old female patient with unilateral Best disease was reviewed. Retinal findings were documented by clinical examination and multimodal imaging. RESULTS: Posterior segment examination of the patient's right eye demonstrated retinal pigment epithelium hypopigmentation and clumping in the central macula beneath a chronic shallow serous retinal detachment (SRD), confirmed by optical coherence tomography. Fluorescein angiography showed central staining with no evidence of focal leakage or choroidal neovascularization, and correlated with the hypoautofluorescence seen on fundus autofluorescence. There was no evidence of choroidal hyperpermeability on indocyanine green angiography, nor was there any neovascularization detected on optical coherence tomography-angiography. The left eye appeared normal with all imaging modalities. CONCLUSION: Best disease is an autosomal dominant disease that is generally bilateral. We present a case of a unilateral Best disease with serous retinal detachment in a patient with a p.G15D mutation in BEST1. Best disease should be considered in the differential diagnosis of serous retinal detachment and may masquerade as central serous chorioretinopathy.

Analysis of kinesin-2 function in photoreceptor cells using synchronous Cre-loxP knockout of Kif3a with RHO-Cre.

PURPOSE: To determine the relationship between the presence of kinesin-2 and photoreceptor cell viability and opsin transport, by generating RHO-Cre transgenic mice and breeding them to mice with a floxed kinesin-2 motor gene. METHODS: Different lines of RHO-Cre transgenic mice were generated and characterized by transgene expression, histology, and electrophysiology. Mice from one line, showing uniform transgene expression, were crossed with Kif3a(flox)/Kif3a(flox) mice. The time courses of photoreceptor Cre expression, KIF3A loss, ectopic opsin accumulation, and photoreceptor cell death were determined by Western blot analysis and microscopy. RESULTS: One of the RHO-Cre lines effected synchronous expression of Cre and thus uniform excision of Kif3a(flox) in rod photoreceptors across the retina. After the neonatal production of CRE and the initiation of KIF3A loss, ectopic accumulation of opsin was detected by postnatal day (P)7, and ensuing photoreceptor cell death was evident after P10 and almost complete by P28. Of importance, the photoreceptor cilium formed normally, and the disc membranes of the nascent outer segment remained normal until P10. CONCLUSIONS: The RHO-Cre-8 mice provide an improved tool for studying gene ablation in rod photoreceptor cells. Regarding kinesin-2 function in photoreceptor cells, the relatively precise timing of events after CRE excision of Kif3a(flox) allows us to conclude that ectopic opsin is a primary cellular lesion of KIF3A loss, consistent with the hypothesis that opsin is a cargo of kinesin-2. Moreover, it demonstrates that KIF3A loss results in very rapid photoreceptor cell degeneration.

Vitreous and aqueous penetration of orally administered moxifloxacin in humans.

OBJECTIVE: To investigate intraocular penetration of moxifloxacin hydrochloride after oral administration. METHODS: Prospective study of 15 patients scheduled for vitrectomy between September and November 2004 at the Barnes Retina Institute, St Louis, MO. Aqueous, vitreous, and serum samples were analyzed from 15 patients after oral administration of 2 tablets containing 400 mg of moxifloxacin. Assays were performed using high-performance liquid chromatography. RESULTS: The mean +/- SD moxifloxacin concentrations in plasma (n = 15), vitreous (n = 13), and aqueous (n = 13) samples were 3.56 +/- 1.31 microg/mL, 1.34 +/- 0.66 microg/mL, and 1.58 +/- 0.80 microg/mL, respectively. Mean +/- SD sampling times after oral administration of the second moxifloxacin tablet for plasma, vitreous, and aqueous were 2.94 +/- 0.81 hours, 3.77 +/- 0.92 hours, and 3.71 +/- 0.89 hours, respectively. The percentages of plasma moxifloxacin concentration in the vitreous and aqueous were 37.6% and 44.3%, respectively. Minimal inhibitory concentrations against 90% levels were exceeded against a wide spectrum of gram-positive and gram-negative pathogens in the vitreous and aqueous. CONCLUSIONS: Moxifloxacin has a spectrum of coverage that encompasses the most common organisms in endophthalmitis. The pharmacokinetic findings of this investigation reveal that orally administered moxifloxacin achieves therapeutic levels in the noninflamed eye. Because of their broad spectrum of coverage, low minimal inhibitory concentration against 90% levels, good tolerability, and excellent oral bioavailability, fourth-generation fluoroquinolones may represent a major advance for managing posterior segment infections.

Generation of Cre transgenic mice with postnatal RPE-specific ocular expression.

PURPOSE: To generate and characterize a constitutively active, RPE-specific, cre-expressing transgenic mouse line. This line can be used to create RPE-specific knockouts by crossing with mice harboring loxP-flanked (floxed) genes. METHODS: A transgene construct was assembled with the BEST1 promoter driving cre expression. Transgenic mice were generated on a C57BL/6 background. Cre expression was assessed by immunofluorescence and Western blot analysis. Cre enzymatic activity was tested by crossing to three lines with floxed DNA regions and detecting deletion of the intervening sequences or through histochemical detection of lacZ activity. Potential cre-mediated toxicity was assessed by retinal histology up to 24 months of age and by electroretinography. RESULTS: The BEST1-cre line with expression in the highest percentage of RPE cells displayed a patchy mosaic expression pattern, with 50% to 90% of RPE cells expressing cre. In mice outcrossed to a mixed B6/129 background, expression was consistently found in 90% of RPE cells. Within the eye, only the RPE cells were immunoreactive with an anti-cre antibody. Maximum cre expression quantified by Western blot analysis occurred at P28. Crosses with three lines containing floxed sequences revealed RPE-specific cre activity in the eye and extraocular expression limited to the testes. Histology and electroretinography showed no cre-mediated RPE toxicity. CONCLUSIONS: This BEST1-cre transgenic line enables generation of RPE-specific knockout mice. The mosaic expression pattern provides an internal control; the non-cre-expressing RPE cells continue to express the floxed genes. These mice should facilitate study of the multifunctional RPE and the generation of mouse models of human retinal disease.

Safety of intravitreal injection of bevacizumab in rabbit eyes.

PURPOSE: To evaluate the safety of intravitreal injection of bevacizumab in rabbits using electrophysiological testing and histopathologic analysis. METHODS: New Zealand albino rabbits were injected in one eye with control antibody (n = 2), 0.05 mL of bevacizumab (n = 3), or 0.2 mL of bevacizumab (n = 3). Electroretinograms were obtained 1 week and 4 weeks after injection. Histologic analysis was performed after completion of the electroretinographic studies. RESULTS: No statistical differences were seen in scotopic and photopic a- and b-wave amplitudes between untreated control and bevacizumab-injected eyes. No histopathologic differences were identified between untreated control and bevacizumab-injected eyes. CONCLUSION: Our study did not find evidence of retinal toxicity from a single intravitreal injection of bevacizumab in rabbits.

Collaborative Initial Glaucoma Treatment Study: a summary of results to date.

PURPOSE OF REVIEW: This review summarizes the key findings from the Collaborative Initial Glaucoma Treatment Study (CIGTS), which was designed to evaluate whether medical therapy or trabeculectomy is the better initial treatment for patients with open-angle glaucoma (OAG). In addition to examining effects on visual field progression, intraocular pressure control, and visual acuity, the study also examined the effects of medical and surgical treatments on quality of life. RECENT FINDINGS: The 4+-year interim outcomes noted no significant difference in visual field loss between the medically and surgically treated patients. Patients assigned to trabeculectomy had lower intraocular pressures, but demonstrated a greater risk for significant loss of visual acuity and a threefold increased rate of cataract progression. Most quality-of-life measurements were similar in the two treatment arms, except local eye symptoms, which were reported more frequently by the surgically treated patients. SUMMARY: Results from CIGTS do not support altering current treatment practices in the initial management of patients with primary open-angle glaucoma.