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David Callanan,1 Rahul N Khurana,2 Raj K Maturi,3,4 Sunil Patel,5 Charles C Wykoff,6 David Eichenbaum,7,8 Arshad M Khanani,9,10 Tarek Hassan,11 Hanh Badger,12 Shraddha Mehta,12 Grace Le,12 Mayssa Attar,13 Jennifer Seal,13 Xiao-Yan Li12,14 1Texas Retina Associates, Arlington, TX, USA; 2Northern California Retina Vitreous Associates, Mountain View, CA, USA; 3Midwest Eye Institute, Indianapolis, IN, USA; 4Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA; 5West Texas Retina, Abilene, TX, USA; 6Retina Consultants of Houston, Retina Consultants of America, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA; 7Retina Vitreous Associates of Florida, St. Petersburg, FL, USA; 8Morsani College of Medicine, University of South Florida, Tampa, FL, USA; 9Sierra Eye Associates, Reno, NV, USA; 10University of Nevada, Reno School of Medicine, Reno, NV, USA; 11Associated Retinal Consultants, Royal Oak, MI, USA; 12Allergan plc, Irvine, CA, USA, at the time of this work; 13Allergan, an AbbVie company, Irvine, CA, USA; 14VivaVision Biotech, Inc, Shanghai, People’s Republic of ChinaCorrespondence: David Callanan, Texas Retina Associates, 801 West Randol Mill Road, Suite 101, Arlington, TX, USA, 76012, Tel +1 817-261-9625, Fax +1 817-261-9586, Email dcallanan@gmail.comPurpose: To evaluate the impact of modifying the abicipar pegol (abicipar) manufacturing process on the safety and treatment effect of abicipar in patients with neovascular age-related macular degeneration (nAMD).Methods: A new process for manufacturing abicipar was developed to reduce host cell impurities. In a prospective, Phase 2, multicenter, open-label, 28-week clinical trial, patients (n=123) with active nAMD received intravitreal injections of abicipar 2 mg at baseline (day 1) and weeks 4, 8, 16, and 24. Outcome measures included proportion of patients with stable vision (< 15-letter loss from baseline; primary endpoint), change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and adverse events.Results: Overall, 8.9% (11/123) of patients experienced intraocular inflammation (IOI) and discontinued treatment. IOI cases were assessed as mild (2.4% [3/123]), moderate (4.9% [6/123]), or severe (1.6% [2/123]) and resolved with steroid treatment. Visual acuity in most patients with IOI (8 of 11) recovered to baseline BCVA or better by study end. No cases of endophthalmitis or retinal vasculitis were reported. Stable vision was maintained for ≥ 95.9% (≥ 118/123) of patients at all study visits. At week 28, treatment-naïve patients showed a greater mean improvement from baseline in BCVA compared with previously treated patients (4.4 vs 1.8 letters) and a larger mean CRT reduction from baseline (98.5 vs 45.5 μm).Conclusion: Abicipar produced using a modified manufacturing process showed a moderately lower incidence and severity of IOI compared with Phase 3 abicipar studies. Beneficial effects of treatment were demonstrated.Keywords: abicipar, age-related macular degeneration, inflammation

Purpose To report the end-of-study results from the Ladder clinical trial of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). Design Multicenter, randomized, active treatment–controlled phase 2 clinical trial. Participants Patients diagnosed with nAMD with a documented response to anti–vascular endothelial growth factor treatment who received study treatment (N = 220). Methods Patients were randomized 3:3:3:2 to treatment with the PDS filled with ranibizumab 10-mg/ml, 40-mg/ml, and 100-mg/ml formulations or monthly intravitreal ranibizumab 0.5-mg injections. Main Outcome Measures End-of-study results for the time to first meeting refill criteria (first refill), mean change from baseline for best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. Results At study end, the mean time on study was 22.1 months (range, 10.8–37.6 months) for all PDS patients. Median time to first refill was 8.7 months, 13.0 months, and 15.8 months, and 28.9%, 56.0%, and 59.4% of patients went 12 months or longer without meeting refill criteria in the PDS 10-mg/ml, 40-mg/ml, and 100-mg/ml treatment arms, respectively. At month 22, the observed mean BCVA change from baseline was ‒4.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒2.3 ETDRS letters, +2.9 ETDRS letters, and +2.7 ETDRS letters in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg treatment arms, respectively. At month 22, the observed mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg treatment arms. No new safety signals were detected during the additional follow-up. Conclusions Over a mean of 22 months on study, vision and anatomic outcomes were comparable between the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms, with a lower total number of ranibizumab treatments with the PDS. The Ladder end-of-study findings were consistent with the primary analysis, and the PDS generally was well tolerated throughout the entire study period. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision.

Purpose: This work reports retinal findings in an adult patient with vitamin B6 deficiency. Methods: A case review of a single patient is presented. Results: A patient with a Roth-type retinal lesion and a history of nonepileptic seizures was found to have lymphocytic colitis. She was treated with pyridoxine, which resolved her seizures and the white-centered hemorrhage. Conclusions: Vitamin B6 deficiency should be considered in the differential diagnosis of patients presenting with white-centered hemorrhages and a history of nonepileptic seizures.

Set in a breathtaking visual landscape made of oversized voxels, a dystopian future unravels slowly around you. Set in a future of job automation, political uncertainty, environmental damage and the breakdown of human connection - all of which has led you here, uploading your consciousness to a machine.

Purpose To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). Design Randomized, double-masked, placebo-controlled, phase 2 study. Participants Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. Methods Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. Main Outcome Measures The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of Results At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose Conclusions Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

Purpose: To evaluate safety and efficacy of the vascular endothelial growth factor binding protein abicipar pegol (abicipar) versus ranibizumab for neovascular age-related macular degeneration. Methods: Phase 2, multicenter, randomized, double-masked comparison (REACH study, stage 3). Patients (n = 64) received intravitreal injections of abicipar 1 mg or 2 mg at baseline, week 4, and week 8 (3 injections) or ranibizumab 0.5 mg at baseline and monthly (5 injections). Results: In the abicipar 1 mg (n = 25), abicipar 2 mg (n = 23), and ranibizumab (n = 16) arms, respectively, least-squares mean best-corrected visual acuity (BCVA) change from baseline was +6.2, +8.3, and +5.6 letters at week 16 (primary endpoint) and +8.2, +10.0, and +5.3 letters at week 20. Least-squares mean central retinal thickness (CRT) reduction from baseline was 134, 113, and 131 μm at week 16 and 116, 103, and 138 μm at week 20. Intraocular inflammation adverse events (AEs), reported in 5/48 (10.4%) abicipar-treated patients, resolved without sustained vision loss or other sequelae. Conclusions: Abicipar demonstrated durability of effect: BCVA and CRT improvements were similar between abicipar and ranibizumab at weeks 16 and 20 (8 and 12 weeks after the last abicipar injection and 4 weeks after the last ranibizumab injection). No serious AEs were reported.

Purpose To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). Design Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. Participants A total of 152 patients (152 eyes) with DME. Methods Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24. Main Outcome Measures The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. Results A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) ( P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively ( P = 0.08). The mean change in CFT was −192.53 μm in the 0.5 mg RBZ group and −170.64 μm in the 2.0 mg RBZ group ( P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. Conclusions At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

To evaluate whether treatment with dexamethasone intravitreal implant (DEX implant) 0.7 mg every 5 months provides a similar average change in best-corrected visual acuity (BCVA) from baseline as ranibizumab 0.5 mg administered as per its European Summary of Product Characteristics in patients with diabetic macular edema (DME). This was a multicenter, open-label, 12-month, randomized, parallel-group, noninferiority study in patients with DME (one eye/patient). The primary efficacy measure was BCVA using the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Secondary efficacy measures included area of leakage on fluorescein angiography and central retinal thickness (CRT) on optical coherence tomography. Baseline patient characteristics were similar in the two treatment groups (DEX implant, n = 181; ranibizumab, n = 182); mean DME duration was ∼33 months. The mean average BCVA change from baseline over 12 months was 4.34 letters with DEX implant and 7.60 letters with ranibizumab. The lower limit of the 95 % confidence interval of the between-group difference was −4.74 letters, and therefore, DEX was demonstrated to be noninferior to ranibizumab based on the prespecified noninferiority margin of 5 letters. At monthly follow-up visits, the percentage of patients with ≥15-letter BCVA gain from baseline ranged from 7.2 to 17.7 % with DEX implant and 4.4 to 26.9 % with ranibizumab. Both DEX implant and ranibizumab effectively reduced CRT and reduced the area of fluorescein leakage. Between-group differences in change from baseline CRT favored DEX implant at 1, 2, 6, and 7 months (p ≤ 0.007) and ranibizumab at 4, 5, 9, and 10 months (p

Purpose: To compare the rate of retinal detachment after acute retinal necrosis in eyes that underwent early vitrectomy versus no early vitrectomy.Methods: Charts of patients (61 eyes) who presented to Texas Retina Associates between January 1, 2006 and December 30, 2014 for acute retinal necrosis were reviewed. Charts with incomplete documentation or follow­up less than 6 months were excluded. Twenty-nine remaining eyes were divided into two groups: early vitrectomy and no early vitrectomy. Primary outcome measure was rate of retinal detachment. Results: Out of 29 eyes, 12 underwent early vitrectomy within 30 days of diagnosis and 17 either underwent vitrectomy after 30 days or did not undergo prophylactic vitrectomy at all. Three out of 12 eyes (25%) developed retinal detachment in the early vitrectomy group versus 10 out of 17 eyes (59%) in the no early vitrectomy group (p = 0.076).Conclusions: Early vitrectomy within 30 days may prevent retinal detachment after acute retinal necrosis.

To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial.Randomized clinical trial with extended follow-up.Review of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically related.A total of 250 eyes (146 patients) had at least 1 implant placed. Median follow-up time after implant placement was 6 years (range 0.5-9.2 years). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval [CI]: 2.4%-9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. Thirty-nine implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%-48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, P.001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or its treatment.There is an increasing risk of dissociation of Retisert implants during follow-up; the risk is greater with removal/exchange surgeries, but the risk of both spontaneous and surgically related events increases with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected.

The authors provide a significant interpretation of the National Eye Institute-sponsored Multicenter Uveitis Steroid Treatment study, in which patients with severe, non-infectious intermediate, posterior, or panuveitis were randomly assigned to receive local treatment using the sutured intravitreal fluocinolone acetonide implant or systemic treatment consisting of oral steroids and conventional steroid-sparing immunosuppression, with a primary outcome of visual acuity at 2 years of follow-up. The authors also present evidence-based guidance for the treatment of noninfectious posterior segment involving uveitis. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:266–268.]

To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU).Randomized, double-masked, placebo-controlled, phase 2 study.Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis.Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo.The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis.At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 μm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 μm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] μm (P = 0.1317) in the subgroup of eyes with CST ≥300 μm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients).Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

BACKGROUND AND OBJECTIVE: Guidance on the use of corticosteroids in the treatment of diabetic macular edema (DME) is lacking. This study aimed to develop a clinically recommended treatment paradigm for DME with emphasis on the role of corticosteroids. PATIENTS AND METHODS: An expert panel of nine retinal specialists in the United States developed consensus recommendations for DME treatment through a modified Delphi process. RESULTS: The panelists typically use intravitreal injections of vascular endothelial growth factor (VEGF) antagonists as first-line treatment of DME and switch patients with an inadequate response to anti-VEGF therapy (failure of best-corrected visual acuity to improve to 20/40 or better because of edema after three to six monthly injections, or a less-than-50% reduction in excess macular thickness after three to four monthly injections) to intravitreal corticosteroid treatment. CONCLUSION: Intravitreal corticosteroids have a potentially useful role in the treatment of patients with DME who have an inadequate response to intravitreal anti-VEGF therapy. [ Ophthalmic Surg Lasers Imaging Retina. 2017;48:291–301.]

Purpose To evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD. Design Clinical trial. Participants Eight hundred thirty-four (73%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. Methods Each patient was genotyped for SNPs rs1061170 ( CFH ), rs10490924 ( ARMS2 ), rs11200638 ( HTRA1 ), and rs2230199 ( C3 ), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). Main Outcomes Measures Genotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, P ≤0.01 was considered statistically significant. Results No statistically significant differences in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing. Conclusions Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti–vascular endothelial growth factor therapy. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy.This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30 mg AA. All patients then received a 0.5 mL AJD of the assigned treatment. Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3, 4, 5, and 6. IOP was measured at each visit as well as best corrected visual acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination, and assessment of any adverse events. In addition, at baseline and at exit, a dilated fundus examination was carried out and the lens was examined using LOCS II criteria.Seventy patients were randomized to treatment. At week 4, eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline. Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg, 16.6%) were not significantly different than for vehicle control. However, IOP for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline, which was statistically significant (P=0.0487). The mean time to treatment failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA, and 30 mg AA groups, respectively. Adverse events were assessed at each post-treatment visit. There were no serious adverse events that were determined to be related to the test article or its administration.AA can be of benefit to some patients requiring treatment with corticosteroids, but suffering from the side effect of elevated IOP.

The purpose of this study was to describe and compare the rates and characteristics of noninfectious vitritis after intravitreal injection of bevacizumab (Avastin, Genentech, South San Francisco, CA), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron, Tarrytown, NY).A retrospective case series evaluated intravitreal injections from 2006 to 2013. Cases of inflammatory response were separated into culture-positive endophthalmitis, noninfectious vitritis (not treated with intravitreal antibiotics), and indeterminate. Noninfectious cases were analyzed for rate, presentation, and clinical course.A total of 66,356 bevacizumab, 26,161 ranibizumab, and 8071 aflibercept injections were screened. The rates of noninfectious vitritis were 0.10% (67 cases) for bevacizumab, 0.02% (6 cases) for ranibizumab, and 0.16% (13 cases) for aflibercept. The differences were statistically significant based on Chi-square analysis (P0.001). Mean differences in visual decline were not significant by Kruskal-Wallis analysis (P = 0.12), but the percentage of patients with any visual decline did vary by medication according to Fisher exact test (P0.05). The percentage of patients with complaints of pain, blurred vision, and subjective floaters was not significantly different by medication based on Fisher exact testing (P = 0.2, P = 0.18, P = 0.16, respectively). Bevacizumab and aflibercept cases tended to present in separate chronological clusters.The results suggest a difference in rates of noninfectious vitritis for antivascular endothelial growth factor medications. Many cases tended to cluster instead of occurring at a consistent rate each year.

Patrick D Williams,1 David Callanan,1 Wayne Solley,1 Robert L Avery,2 Dante J Pieramici,2 Tom Aaberg31Texas Retina Associates, Dallas, TX, 2California Retina Consultants and Research Foundation, Santa Barbara, CA, 3Retinal Associates, Grand Rapids, MI, USAPurpose: This prospective multi-center pilot study compares the use of half-fluence photodynamic therapy combined with ranibizumab with ranibizumab monotherapy for the treatment of neovascular age-related macular degeneration.Methods: All patients presenting with untreated subfoveal neovascular age-related macular degeneration were considered for inclusion. Patients were randomized to receive either ranibizumab with half-fluence photodynamic therapy or ranibizumab alone. Patients in the ranibizumab alone group were given three consecutive monthly ranibizumab injections and were followed monthly. They were treated with ranibizumab as needed, based on clinical discretion, using vision and optical coherence tomography. Patients in the combined group were given one same-day combined ranibizumab and half-fluence (25 j/cm2) photodynamic therapy treatment and were treated monthly as needed. Outcomes included changes in standardized visual acuity, optical coherence tomography foveal thickness, and percentage of as-needed injections to maintenance examinations.Results: Fifty-six out of 60 enrolled patients completed the twelve month primary outcome visit; this consisted of 27 patients receiving ranibizumab alone and 29 receiving combined treatment. The average age was 79.1 for the ranibizumab alone group and 79.3 for the combined group. The mean visual acuity in the ranibizumab alone group improved from 52.9 Early Treatment of Diabetic Retinopathy letters initially to 62.8 letters at twelve months. The mean visual acuity in the combined group improved from 49.2 letters to 51.8 letters at twelve months. The differences in visual acuity improvements were not statistically significant based on a two-tailed t-test (P = 0.2). Due to the presence of outliers in each group, a Mann–Whitney U test was performed to confirm the results (U = 325; P = 0.28). The mean optical coherence tomography foveal thickness improved 92.5 microns and 106.7 microns in the ranibizumab alone and the combined group, respectively. The difference was not significant based on a two-tailed t-test (P = 0.6). The ranibizumab alone group received an average of 6.8 injections, while the combined group received an average of three injections. This difference was not significant based on a chi-square test (P = 0.11).Conclusion: The groups appeared similar based on statistical analysis, but larger studies are needed to determine possible small differences between combination therapy and monotherapy.Keywords: ranibizumab, macular degeneration, photodynamic therapy, verteporfin, choroidal neovascularization, anti-vegf

Purpose We studied the 3-year efficacy and safety results of a 4-year study evaluating fluocinolone acetonide (FA) intravitreal implants in eyes with persistent or recurrent diabetic macular edema (DME). Design Prospective, evaluator-masked, controlled, multicenter clinical trial. Participants We included 196 eyes with refractory DME. Methods Patients were randomized 2:1 to receive 0.59-mg FA implant (n = 127) or standard of care (SOC additional laser or observation; n=69). The implant was inserted through a pars plana incision. Visits were scheduled on day 2, weeks 1, 3, 6, 12, and 26, and thereafter every 13 weeks through 3 years postimplantation. Main Outcome Measures The primary efficacy outcome was ≥15-letter improvement in visual acuity (VA) at 6 months. Secondary outcomes included resolution of macular retinal thickening and Diabetic Retinopathy Severity Score (DRSS). Safety measures included incidence of adverse events (AEs). Results Overall, VA improved ≥3 lines in 16.8% of implanted eyes at 6 months ( P =0.0012; SOC, 1.4%); in 16.4% at 1 year ( P =0.1191; SOC, 8.1%); in 31.8% at 2 years ( P =0.0016; SOC, 9.3%); and in 31.1% at 3 years ( P =0.1566; SOC, 20.0%). The number of implanted eyes with no evidence of retinal thickening at the center of the macula was higher than SOC eyes at 6 months ( P P P =0.016), and 3 years ( P =0.861). A higher rate of improvement and lower rate of decline in DRSS occurred in the implanted group versus the SOC group at 6 months ( P =0.0006), 1 year ( P =0.0016), 2 years ( P =0.012), and 3 years ( P =0.0207). Intraocular pressure (IOP) ≥30 mmHg was recorded in 61.4% of implanted eyes (SOC, 5.8%) at any time and 33.8% required surgery for ocular hypertension by 4 years. Of implanted phakic eyes, 91% (SOC, 20%) had cataract extraction by 4 years. Conclusions The FA intravitreal implant met the primary and secondary outcomes, with significantly improved VA and DRSS and reduced DME. The most common AEs included cataract progression and elevated IOP. The 0.59-mg FA intravitreal implant may be an effective treatment for eyes with persistent or recurrent DME. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

To evaluate outcomes in birdshot chorioretinopathy following intravitreal implantation of a fluocinolone acetonide-containing drug delivery device.Retrospective, multicenter, interventional case study.University- and community-based tertiary care. Twenty-two HLA-A29+ birdshot patients (36 eyes) were implanted with a sustained-release corticosteroid device and followed for up to 3 years. Main outcome measures were Snellen acuity, intraocular inflammation, adjunctive therapy, cataract, ocular hypertension, or glaucoma. Paired Wilcoxon statistics were used to analyze visual acuities; paired McNemar statistics were used to analyze presence or absence of other outcomes.Nineteen of 22 patients (32 eyes) completed 12 months of follow-up with improvement in median visual acuity (P=.015). Prior to implantation, 18 of 22 patients (82%) received immunosuppressive therapy versus 1 of 19 (5%) by 12 months (P.001). Eyes with zero vitreous haze increased from 7 of 27 scored eyes (26%) at baseline to 30 of 30 eyes (100%) by 12 months (P.001). Cystoid macular edema decreased from 13 of 36 eyes (36%) at baseline to 2 of 32 eyes (6%) at 12 months (P=.006). Five of 24 phakic eyes at baseline exited the study before surgery; all other eyes received cataract surgery. One hundred percent of study eyes had ocular hypertension, required intraocular pressure-lowering therapy, or had glaucoma surgery by 12 months.Implantation of a fluocinolone acetonide-containing intraocular device in birdshot chorioretinopathy can improve vision, control inflammation, and eliminate systemic therapy. There is a high incidence of cataract progression and intraocular hypertension or glaucoma.

To evaluate the safety and efficacy of preservative-free triamcinolone (TRIESENCE(R) suspension) for visualization during pars plana vitrectomy.This phase III, observer-masked study was conducted in 6 centers by 10 surgeons and enrolled 60 patients undergoing pars plana vitrectomy. Preservative-free triamcinolone (up to 4 mg) was administered to all patients to enhance visualization of vitreous and membranes. During each surgery, video recordings captured visualization pre- and postinstillation of preservative-free triamcinolone. An independent, masked reader evaluated the videos for the degree of visualization using a five-point scale ranging from 0 (not visible) to 4 (clearly delineated). Surgeons used a five-point scale ranging from "strongly disagree" to "strongly agree" to assess whether preservative-free triamcinolone improved visualization.In 59 of 60 cases, the masked reader's scores for visualization of posterior segment structures were higher (i.e., structures were more clearly visible) after instillation of preservative-free triamcinolone. The preinstillation mean visualization score was 0.5 compared to 3.7 postinstillation (P0.0001). Greater than 90% of surgeon evaluations agreed or strongly agreed that preservative-free triamcinolone enhanced visualization of posterior segment structures. No safety issues were identified.Preservative-free triamcinolone (TRIESENCE(R) suspension) was well tolerated and effectively enhanced visualization of posterior segment structures during pars plana vitrectomy.

PURPOSE To describe the efficacy of nepafenac ophthalmic suspension 0.1% (Nevanac; Alcon Laboratories, Inc.) for treating cystoid macular edema (CME) resulting from uveitis. DESIGN Interventional case series METHODS : Three patients with a history of decreased visual acuity due to uveitic CME despite previous treatment with topical steroids or traditional nonsteroidal antiinflammatory drugs, intravitreal triamcinolone acetonide (Kenalog; Bristol-Myers Squibb), or immunosuppressive agents were given topical nepafenac 0.1%. Patients were monitored for clinical improvement, decreased retinal thickness by optical coherence tomography, and improved Snellen visual acuity. RESULTS For all three patients, treatment with topical nepafenac for 4 weeks to 3 months led to improvement in visual acuity and decrease in retinal thickness. CONCLUSIONS The improved visual acuity and decreased retinal thickness in these patients suggest that nepafenac is an effective treatment of inflammation and CME in the posterior segment of the eye for patients with chronic uveitis.

Cystoid macular edema (CME), a common complication following cataract surgery, is routinely medically treated with topical nonsteroidal anti-inflammatory drugs (NSAIDs), alone or in combination with steroids. In this paper, we describe 6 patients with CME and 1 patient with diabetic macular edema (DME), all of whom were treated with nepafenac 0.1%, a novel prodrug NSAID. Three (3) patients with acute CME following cataract surgery were treated for 3-4 weeks with nepafenac 0.1%, with or without concomitant steroids. Both retinal thickness and visual acuity improved in all 3 cases. The 3 patients with chronic CME, each of whom had been previously treated with steroids with or without concomitant NSAID therapy, were started on nepafenac 0.1% three times daily. Retinal thickness and visual acuity improved in each case, except for 1 patient with 20/25 pretreatment visual acuity. The mean improvement in visual acuity of all 6 CME patients was 2.5 lines and the mean decrease in retinal thickness was 282.8 microm. The patient with DME also showed improvement in retinal thickness and visual acuity after 6 months of treatment with nepafenac. These clinical data strongly suggest that nepafenac 0.1% is a promising drug for the treatment of posterior segment inflammation, including CME, and warrants further investigation.

To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME) and a central subfield thickness (CFT) of ≥250 μm on time-domain optical coherence tomography.DesignRandomized, controlled, multicenter clinical trial.Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n=77) or 2.0 mg (n=75) RBZ. Study eyes received 6-monthly injections.Main outcome measuresThe primary outcome measure was the mean change in best corrected visual acuity (BCVA) at month 6. Secondary outcomes included the incidence and severity of systemic and ocular adverse events and the mean change in CFT from baseline.In all, 152 eyes (152 patients) were randomized in the study. At month 6, the mean improvement from baseline BCVA was +9.43 letters in the 0.5 mg RBZ group and +7.01 letters in the 2.0 mg RBZ group (P=0.161). At month 6, one death occurred in the 0.5 mg RBZ group and three deaths in the 2.0 mg RBZ group, all due to myocardial infarction in subjects with a prior history of heart disease. Mean CFT was reduced by 168.58 μm in the 0.5 mg RBZ group and by 159.70 μm in the 2.0 mg RBZ group (P=0.708).There was no statistically significant difference in the mean number of letters gained between the 0.5 and 2.0 mg RBZ groups through month 6. In this DME study population, high-dose RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Prospective cohort study within a randomized clinical trial.The 1185 CATT participants.Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Presence of SHRM, as well as location and size, and associations with VA, scar, and GA.Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P0.05).In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.

Chronic noninfectious posterior segment uveitis refers to inflammation of the retina, choroid, vitreous, or optic nerve, and may result in permanent vision loss. The inflammation can be constant, or characterized by periodic exacerbations on an underlying baseline of inflammation. Recent studies indicate that this vision loss often results from cumulative damage over multiple recurrences of inflammation, rather than from a single initiating event. Most forms of local therapy provide only transient suppression of inflammation, and the use of systemic agents may be limited by serious side effects. The course of uveitis may, therefore, be marked by recurrent episodes of inflammation, each contributing to progressive and permanent loss of visual acuity. The goal of uveitis treatment should not only be to suppress inflammation when it recurs but also to attain complete remission of inflammation, and thus prevent complications such as cystoid macular edema (CME) and permanent cumulative damage. The RETISERT intravitreal implant offers sustained local control of inflammation without the systemic side effects that limit standard immunosuppressive and oral corticosteroid therapies. The recommendation of the expert panel was that RETISERT is a useful addition to the armamentarium for the treatment of chronic noninfectious posterior segment uveitis and may help to prevent cumulative damage from repeated occurrences of inflammation, especially when vision can be improved rather than only stabilized.

Purpose To report the interim 34-week safety and efficacy results of a 3-year study to evaluate an investigational intravitreal fluocinolone acetonide (FA) implant in patients with noninfectious posterior uveitis. Design Prospective, dose-masked, dose-randomized, historically controlled, multicenter trial in patients with unilateral or bilateral disease. Participants A total of 278 patients with recurrent noninfectious posterior uveitis were randomized to receive a 0.59-mg (n = 110) or 2.1-mg (n = 168) implant. In patients with bilateral disease, the more severely affected eye received the implant. Methods The implant was inserted surgically into the vitreous cavity through a pars plana incision. Follow-up visits were scheduled on day 2, week 1, and then every 4 to 6 weeks through 34 weeks after implantation. Systemic, periocular, and topical therapies were reduced as allowed by the clinical response. Main Outcome Measures The primary efficacy outcome was a comparison of the recurrence rate in the implanted eye from the 34 weeks before implantation to the 34 weeks after implantation. Visual acuity (VA), need for adjunctive therapy, and safety also were assessed. Results Combining both doses, the FA implant reduced the rate of recurrences from 51.4% in the 34 weeks preceding implantation to 6.1% postimplantation ( P P P ≤0.0001 in all cases). At week 34, 51.1% of implanted eyes required ocular antihypertensive drops, and 5.8% underwent glaucoma filtering surgery. Lens opacity scores increased by ≥2 grades in 19.8% of phakic implanted eyes, and 9.9% required cataract surgery. There were no statistically significant differences in any of the parameters studied for the 0.59-mg implant, compared with the 2.1-mg implant. Conclusions The FA implant significantly reduced uveitis recurrences, improved VA, and decreased the need for adjunctive therapy in the studied patient population. The most common side effects included increased intraocular pressure and cataract progression.

Purpose To review the distinctive and shared features of the white dot syndromes, highlighting the clinical findings, diagnostic test results, proposed etiologies, treatments, and prognosis. Design Review. Methods Review of the literature. Results Common white dot syndromes are reviewed, including acute posterior multifocal placoid pigment epitheliopathy, birdshot chorioretinopathy, diffuse unilateral subacute neuroretinitis, multiple evanescent white dot syndrome, multifocal choroiditis with panuveitis, serpiginous choroiditis, and acute zonal occult outer retinopathy. Conclusions The white dot syndromes are a group of disorders characterized by multiple whitish-yellow inflammatory lesions located at the level of the outer retina, retinal pigment epithelium, and choroid. For clinicians and researchers alike, they present significant diagnostic and therapeutic challenges.

Purpose To describe a case of pituitary adenoma presenting as bilateral serous retinal detachments and the histopathologic and hematologic evidence of a linkage. Methods Record review for a single patient including testing to determine the etiology of the retinal detachments. Results The retinal detachments were determined to be a variant of central serous chorioretinopathy. A pituitary adenoma was discovered by neuroimaging. Histopathologic analysis of the tumor and serum cortisol levels demonstrated the lesion to be a cortisol-secreting adenoma. Conclusion Bilateral serous retinal detachments are a variant of central serous chorioretinopathy and a rare presentation of pituitary adenoma.

Keywords: Photomedicine group Reference LPAS-ARTICLE-2001-009 Record created on 2007-07-20, modified on 2016-08-08

Purpose: The authors describe the clinical feature of ten patients with a new syndrome characterized by the presence of retinal vasculitis, multiple macroaneurysms, neuro-retinitis, and peripheral capillary nonperfusion. Methods: The authors evaluated ten patients identified to have clinical features compatible with the syndrome of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN). Clinical examination findings, sequential fundus photographs (when available), fluorescein angiograms, systemic investigations, response to therapy, and visual outcomes were reviewed. Results: Seven eyes of four patients sustained a marked decrease in visual acuity of 20/200 or worse. Visual loss was due to a combination of an exudative maculopathy and sequelae of retinal ischemia. Capillary nonperfusion was seen in all ten patients and was severe enough to warrant panretinal laser photocoagulation in six patients. Systemic investigations were uniformly noncontributory. Oral prednisone appears to have little beneficial effects on patients with this disorder. Conclusions: Patients with IRVAN have characteristic retinal features that readily identify this syndrome. An increased awareness of this rare syndrome may help to identify sight-threatening complications at an earlier stage. The authors caution against extensive medical investigations. Ophthalmology 1995;102:1089-1097

The ocular histoplasmosis syndrome consists of punched-out, atrophic chorioretinal lesions, and peripapillary scarring in the absence of vitreal inflammation. Choroidal neovascularization is the cause of significant visual loss in involved eyes and is estimated to occur in up to 5% of affected eyes. An experimental primate model has given us a better understanding of the possible etiology and pathogenesis. Laser therapy for extrafoveal and juxtafoveal choroidal neovascularization has been shown to be effective. Recent advances in surgical technique and instrumentation have demonstrated the potential for the successful treatment of subfoveal choroidal neovascularization. The surgical specimens obtained from this approach have allowed for the study of the active process of neovascularization in this disease. This report summarizes our current knowledge regarding the pathogenesis and epidemiology of ocular histoplasmosis and the treatments currently utilized in the management of its associated choroidal neovascularization.

PURPOSE To evaluate the utility of oral methotrexate (MTX) for the treatment of chronic central serous chorioretinopathy (CSCR). METHODS Retrospective review of all eyes of patients on oral MTX as treatment for chronic CSCR in three different centers. Visual acuity as well as optical coherence tomography central macular thickness and total volume parameters were analyzed. Complete blood count and serum chemistry results were monitored. RESULTS Nine eyes of 9 patients treated with MTX for chronic CSCR met the criteria for analysis. Mean duration of CSCR was 28 months (range, 3-94 months). Mean starting dose of oral MTX was 7.04 mg (range, 5-10 mg), and mean final dose was 7.27 mg (range, 5-10 mg). The mean duration of treatment was 89 days. Mean visual acuity improved from 20/67 at baseline to 20/35 at 8 weeks (P < 0.01, paired t-test). Mean central macular thickness improved from 309 μm to 213 μm at 8 weeks (P < 0.01, paired t-test). Mean total macular volume improved from 8.14 to 7.21 at 8 weeks (P ≤ 0.02, paired t-test). Eighty-three percent of the patients achieved total resolution of subretinal fluid. No MTX-associated toxicity was evident. CONCLUSION Methotrexate may have a role in the treatment of chronic CSCR as evidenced by these results. A randomized controlled clinical trial is warranted to better understand the effects of MTX in these patients.

To identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes.Cohort study using randomized controlled trial data.Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA.Baseline factors significantly associated with reduced BCVA included age ≥50 vs50 years; posterior vs intermediate uveitis; uveitis duration10 vs6 years; anterior chamber (AC) flaregrade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P.001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or10 vs6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening.Intermediate, posterior, and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation.

Purpose: Accidental skin puncture carries the risk of both hepatitis B and human immunodeficiency virus transmission. There have been studies of the incidence of these skin punctures in general surgery, but no study has focused on ophthalmic surgery. Method: All incident reports of skin punctures in the Bascom Palmer Eye Institute operating rooms from January 1990 through November 1991 were reviewed retrospectively. The incidence of skin puncture also was studied prospectively from December 1991 through May 1992. During the prospective phase, the healthcare worker was asked to complete an anonymous form regarding the instrument involved, whether it was clean or contaminated, the persons involved, and whether the room lights were on or off. Results: There were 37 such occurrences in 14,878 operations (0.25%) during the retrospective study and 12 in 4246 operations (0.28%) in the prospective period. In only one case was the instrument contaminated by contact with a patient known to have positive serology for the human immunodeficiency virus. There were no documented seroconversions of healthcare personnel for either hepatitis B or human immunodeficiency virus. In 63% of these occurrences, the penetrating instrument was known to be definitely contaminated with the patient's blood. Only one person was handling the instrument 84% of the time. Conclusion: The low but present danger to ophthalmic personnel during surgical procedures justifies precautions to decrease the occurrence of skin punctures.

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

The purpose of this study was to determine the frequency and characteristics of sterile intraocular inflammation occurring after intravitreal bevacizumab (IVB) (Avastin, Genentech, South San Francisco, CA) injection and to analyze whether a repeat IVB or intravitreal ranibizumab (IVR) (Lucentis, Genentech) injection after an episode of postinjection inflammation elicits a repeat inflammatory reaction.A retrospective case series evaluated 16,166 IVB injections administered between 2006 and 2008. Patients with postinjection inflammation were analyzed for the number of previous injections, time from prior injection to incident injection, presenting signs and symptoms, treatment, visual acuity, time from onset to resolution and recovery of vision, and whether repeat injection caused recurrent inflammation.The incidence of sterile intraocular inflammation after IVB injection resolving with topical antibiotics and steroids alone was 0.27% (44 of 16,166). The average number of prior IVB injections in the ipsilateral eye was 2.8 ± 0.4 with 10 cases occurring with first-time injections. The average time from injection to recovery of visual acuity was 53 ± 18 days, and from injection to resolution of inflammation was 37 ± 5 days. Thirty-six cases received subsequent IVB or intravitreal ranibizumab, and there were three episodes of recurrent inflammation with repeat IVB. The average follow-up was 17 ± 1 month.In most cases of sterile intraocular inflammation after IVB, visual acuity returned to baseline, and intraocular inflammation rarely recurred with repeat IVB or intravitreal ranibizumab.

Birdshot retinochoroidopathy is an uncommon intraocular inflammatory disorder (uveitis) comprised of depigmented spots in the choroid along with vitreous cells [1, 2]. Anterior inflammation may be present, and the disease is typically bilateral and symmetric. Retinal capillary hyperpermeability and resultant cystoid macular edema are common [3]. Some reports have suggested stability of visual acuity after an initial inflammatory stage [4, 5]. Others, however, have described a chronic and unrelenting course [1, 2, 6–8]. Serial electroretinograms and visual fields support progressive deterioration of retinal function, even in cases not considered to have active inflammation [6, 8]. Although retinal atrophy has been mentioned in birdshot retinochoroidopathy [6, 7], there is only one case report specifically describing macular atrophy [9]. Autofluorescence imaging has demonstrated the extent of retinal pigment epithelium (RPE) atrophy, even in regions without hypopigmented birdshot lesions [10]. Histopathology has been performed in birdshot retinochoroidopathy, but without mention of retinal thickness away from the fovea or retinal atrophy [11]. Optical coherence tomography (OCT) of birdshot retinochoroidopathy has revealed features of the choroidal lesions [9, 12]. OCT and retinal thickness analysis were used to evaluate systemic steroid treatment in birdshot retinochoroidopathy in a case report, but retinal thickness was normal away from the fovea [12]. Recent advances in electroretinography and optical imaging allow for more detailed analysis of the macula than previously possible. The multifocal (mf) ERG produces a detailed topographical map of retinal function, while frequency domain (fd) OCT provides a precise analysis of layer-by-layer structure within the macula. The purpose of this study is to evaluate macular atrophy by fdOCT in patients with birdshot retinochoroidopathy and to compare the resulting thickness measures with visual acuity and mfERG.

Background: Several recent articles have described syndromes in which there is enlargement of the blind spot associated with retinal lesions. These have included the multiple evanescent white dot syndrome, acute macular neuroretinopathy, acute idiopathic blind spot enlargement syndrome, and multifocal choroiditis or pseudo presumed ocular histoplasmosis syndrome (pseudo POHS). Methods: The authors reviewed the records of seven patients in whom signs and symptoms of acute enlargement of the blind spot and pseudo POHS developed. Results: All seven patients had photopsia accompanying enlargement of the blind spot during their illness. Four had transient white spots as seen in the multiple evanescent white dot syndrome. All presented with or developed chorioretinal scars or neovascularization similar to that seen in multifocal choroiditis or pseudo POHS. In four of the seven patients, POHS-like scars developed only in the eye that was symptomatic with blind spot enlargement and photopsia. Five of the 7 had visual acuity of 20/25 or better at the last follow-up. Conclusion: It would appear that there is an overlap in the clinical findings of all of these syndromes and that there may be a common link in their etiology.

Macular edema as a result of diabetic retinopathy can lead to central vision loss. It is one of the major causes of visual loss in the United States,1 with ∼4.1 million Americans (age ≥40 years) estimated to have diabetic retinopathy.2 Vision-threatening diabetic retinopathy, which includes both proliferative diabetic retinopathy and diabetic macular edema (DME), is estimated to occur in ∼899,000 persons with the majority having type 2 diabetes.2 The estimated proportions of persons with diabetes affected by macular edema are type 1 diabetes, 20%; type 2 diabetes, using insulin, 25%; and type 2 diabetes, not using insulin, 14%.3 The prevalence of diabetes is expected to substantially increase by 2020 with the increasing prevalence of diabetes mellitus in the aging U.S. population. When macular edema is established, focal laser photocoagulation reduces the risk of moderate visual loss (loss of ≥15 letters from baseline on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity charts) by 50%.4 However, treatment is often not associated with improvement in visual acuity. Furthermore, the focal laser burns may result in an increase in atrophy of the retinal pigment epithelium and progressive enlargement of the initial focal scars of laser photocoagulation and eventually visual loss with central scotomas and decreased color vision.5 Reduction of tissue destruction from laser burns while maintaining the beneficial treatment effect would potentially reduce this long-term risk of laser treatment. These adverse side effects of the continuous wavelength laser used in the ETDRS technique may theoretically be diminished by using a micropulse diode laser grid, which would result in subthreshold burns with the accompanying reduction of damage from photocoagulation to the retinal pigment epithelium.6,7 This technique has been evaluated in case series without concurrent controls.8–10 This study was designed to compare the micropulse diode grid laser with the standard ETDRS focal laser technique using the continuous wavelength laser. Animal models of diabetic retinopathy demonstrate that inflammation plays an important role in diabetic retinopathy.11 In early onset of diabetic retinopathy, up-regulation of cyclo-oxygenase-2 (COX-2) occurs in retinal cells. This results in elevated prostaglandin production, leading to an increased expression of vascular endothelial growth factor and an increased risk of vascular leakage and retinal neovascularization.12 High doses of aspirin and intermediate doses of COX-2 inhibitors (celecoxib) were apparently beneficial in early experimental diabetic retinopathy.13 Other investigations have shown that periocular celecoxib-poly (lactide-co-glycolide) microparticles inhibited elevations of retinal vascular endothelial growth factor and other factors for as long as 60 days in a diabetic animal model.14 Cyclo-oxygenase-2 inhibitors have been demonstrated to have antiangiogenic effects in a rat model of ischemic proliferative retinopathy,15 and COX-2 expression is evident in human retina of individuals with diabetes.8 These data suggest that treatment with a COX-2 inhibitor may be beneficial in the treatment of DME. The purpose of this study was to gather pilot data to evaluate the feasibility of mounting a larger multicenter study to evaluate the efficacy of celecoxib (a COX-2 inhibitor and a nonsteroid anti-inflammatory drug) and of a modified laser photocoagulation technique for the treatment of DME.

The mainstay in the treatment of ocular inflammation, either post-surgical or endogenous, is the use of steroids. While these agents effectively address inflammation, they are not without their risks, including ocular hypertension and acceleration of cataract formation. The most notorious culprits are the strong steroids, such as prednisolone acetate and betamethasone. This review aims to cover the biochemistry and drug development of difluprednate, a novel synthetic strong steroid emulsion. In vivo pharmacokinetics as well as ocular distribution and metabolism are discussed, followed by a comprehensive summary of phase I, II, and III clinical trials evaluating safety and efficacy in patients suffering from postoperative inflammation or anterior uveitis. The objective is to provide an increased familiarity with this newly approved medication as a welcome addition to the ophthalmologist's armamentarium.

Objective To evaluate the intraocular pressure (IOP)–lowering potential of anecortave acetate (AA) in eyes with steroid-related ocular hypertension inadequately controlled with the maximal tolerated or appropriate medical therapy. Design Uncontrolled case series. Methods A total of 8 eyes of 7 subjects with medically uncontrolled IOP following intravitreal or sub-Tenon injections of triamcinolone acetonide were included. All received an 0.8-mL anterior juxtascleral depot of 3% AA solution (24 mg) under topical anesthesia. The IOP was assessed weekly for the first month, then monthly for a minimum of 1 year. Results The mean baseline IOP was 39.9 mm Hg. After 1 week, the mean IOP decreased 12 mm Hg (29%; P = .005) and by 1 month, the mean IOP had decreased 14.1 mm Hg (34.5%; P = .003) from baseline. Four eyes required surgical intervention despite a decrease in IOP because of markedly elevated initial IOP and the degree of preexisting glaucomatous optic neuropathy. We observed no adverse events. Conclusions An anterior juxtascleral depot of AA lowers IOP substantially in some eyes with medically uncontrolled steroid-related ocular hypertension. Further study is warranted to clarify the role of AA in treating this condition as well as other forms of glaucoma.

Male-specific, H-Y antigen is a widely utilized antigen system for analyzing the role of non-MHC transplantation antigens in graft rejection. In this study, we examined the role of H-Y antigen in corneal graft rejection. Orthotopic corneal grafts from male LBNF1 rats were transplanted to syngeneic female LBNF1 recipients. The male corneal grafts survived beyond 100 days on naive female recipients. In other experiments, hosts bearing clear male corneal grafts and systemically immunized with subcutaneous inoculations of male splenocytes followed by full-thickness male skin grafts failed to reject their corneal grafts, even though the male skin grafts were swiftly rejected. The inability of female hosts to reject existing male corneal grafts suggested that the cornea failed to express H-Y transplantation antigen. Further experiments, however, revealed that male-specific antigen was expressed on corneal grafts. Hosts bearing clear male grafts in the left eye rejected subsequent male skin grafts and promptly rejected male corneal grafts transplanted to the contralateral eye. Interestingly, the original male corneal grafts remained clear during the rejection of both the skin graft and the second corneal graft. The results indicate that corneal grafts representing minor histocompatibility disparities enjoy immunologic privilege in the naive host, even if the host is subsequently immunized systemically.

Objectives: To evaluate the safety and efficacy of 0.59-mg and 2.1-mg fluocinolone acetonide (FA) intravitreous implants in noninfectious posterior uveitis. Design: A 3-year, multicenter, randomized, historically controlled trial of the 0.59-mg FA intravitreous implant in 110 patients and the 2.1-mg FA intravitreous implant in 168 patients. Main Outcome Measures: Recurrence rate, vision, and complications. Results: Uveitis recurrence was reduced in implanted eyes from 62% (during the 1-year preimplantation period) to 4%, 10%, and 20% during the 1-, 2-, and 3-year postimplantation periods, respectively, for the 0.59-mg dose group (P