Allen Chiang

The dexamethasone drug delivery system: Indications and evidence

IntroductionThe Ozurdex® (Allergan Inc., Irvine, CA, USA) dexamethasone drug delivery system (DDS) was recently developed as a biodegradable intravitreal implant to provide sustained delivery of 700 μg of preservativefree dexamethasone to the retina and vitreous, and is approved by the United States Food and Drug Administration (FDA) for the treatment of macular edema associated with retinal vein occlusion, as well as for noninfectious posterior uveitis. This review summarizes the rationale behind the development of the dexamethasone DDS, evidence for its use in various clinical scenarios, and compares its efficacy to other available treatment options.MethodsPublished data regarding the dexamethasone DDS as well as unpublished data that has been presented at national meetings were reviewed.ResultsThe dexamethasone DDS has evidence for efficacy in multiple clinical situations, including macular edema associated with retinal vein occlusion (RVO), macular edema associated with uveitis or Irvine-Gass syndrome, diabetic macular edema in vitrectomized eyes, persistent macular edema, noninfectious vitritis, and as adjunctive therapy for age-related macular degeneration. Safety concerns include cataract formation and intraocular pressure elevation that is most often temporary and amenable to medical management.ConclusionsThe dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.

Predictors Of Anti-vegf-associated Retinal Pigment Epithelial Tear Using Fa And Oct Analysis

Purpose: To identify fluorescein angiography and optical coherence tomography (OCT) predictors for retinal pigment epithelial (RPE) tear in eyes with pigment epithelium detachment (PED) associated with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor (VEGF) modulating therapy. Design: Retrospective comparative case series. Methods: In a single institutional center, 60 consecutive patients with PED and neovascular age-related macular degeneration treated with VEGF modulating therapy (either pegaptanib, bevacizumab, or ranibizumab) for more than a 27-month period were included in the study. Fluorescein angiography (FA) and OCT imaging was performed before and after anti-VEGF therapy. Formal statistical analysis comparing the tear group to the nontear group was performed to identify high-risk features for RPE tear. Results: RPE tear rate for eyes with vascularized PED receiving anti-VEGF therapy was 17% (10/60). There were highly statistically significant differences in the median PED size on fluorescein angiography (greatest linear diameter) (3.2 mm versus 1.8 mm, respectively; P < 0.001) and in the median maximum PED height on OCT (394 &mgr;m versus 149 &mgr;m, respectively; P = 0.001) between the tear group and nontear group. There was also a significant difference in terms of the presence of subretinal fluid on OCT between the two groups (87.5% versus 39%, respectively; P = 0.019). Conclusion: Large PED basal diameter and vertical height are correlated with an increased risk of developing an RPE tear after anti-VEGF therapy. Patients with large vascularized PED by fluorescein angiography and/or OCT analysis should be alerted of the risk for vision loss due to RPE tear after anti-VEGF therapy.

Preferred therapies for neovascular age-related macular degeneration.

Purpose of review This report reviews the current treatment strategies and ongoing clinical trials in the treatment of neovascular age-related macular degeneration (AMD). Recent findings The functional and anatomic outcomes achieved in the pivotal ranibizumab trials with monthly injections set the standard for comparison. Since then, various modified dosing regimens with the aim of lessening the treatment burden associated with monthly injections have been investigated. Combination therapy incorporating photodynamic therapy and antivascular endothelial growth factor (anti-VEGF) therapy may represent an alternative treatment approach and randomized multicenter clinical trials are ongoing. In addition, new pharmacologic agents like VEGF Trap-Eye are being developed and investigated; preliminary 1-year results with VEGF Trap-Eye are encouraging. Summary Ranibizumab or bevacizumab monotherapy remains the preferred therapy in the management of neovascular AMD at the present time. Ongoing clinical trials will help determine the efficacy of ranibizumab relative to bevacizumab, evaluate the long-term efficacy and safety of combination therapy modalities, and assess the role of new pharmacologic agents.

A New Grading System For Retinal Pigment Epithelial Tears

Purpose: The purpose of this study was to assess the prognostic value of a new grading system for retinal pigment epithelium (RPE) tears that developed after antivascular endo-thelial growth factor (VEGF) therapy for exudative age-related macular degeneration. Methods: The authors performed a retrospective review of consecutive eyes that developed an RPE tear after intravitreal injection of an anti-VEGF agent (pegaptanib, bevacizumab, or ranibizumab) within a 4.5-year period (January 2005 to January 2009) at a single center. Fundus photography, fluorescein angiography, and optical coherence topography were studied for each case of RPE tear, and using fluorescein angiography analysis, a measurement of greatest linear diameter (millimeter) was obtained and a grading scale devised. The grade of RPE tear was correlated with visual and anatomical outcomes and response to continued anti-VEGF therapy. Results: Twenty-one eyes from 20 patients were evaluated in this study. Retinal pigment epithelium tears were graded from one to four based on the greatest length in the vector direction of the tear and involvement of the fovea. Nineteen percent (n = 4) of eyes had Grade 1 tears (diameter smaller than 200 μm), 14% (n = 3) had Grade 2 tears (diameter between 200 μm and 1-disk diameter), 19% (n = 4) had Grade 3 tears (diameter greater than 1-disk diameter), and 48% (n = 10) had Grade 4 tears (Grade 3 tears that involved the foveal center). Lower grade tears were more likely to have better visual acuity and better response to continued anti-VEGF therapy and less likely to develop a disciform scar but were at risk of progressing to a higher grade tear over time. Conclusion: The grading of RPE tears according to greatest linear diameter may have prognostic value in predicting visual acuity and anatomical outcome with or without continued anti-VEGF therapy. Lower grade tears have better visual acuity and response to anti-VEGF therapy. Grade 4 tears have a very poor prognosis with or without anti-VEGF therapy.

Postoperative posterior segment complications in eyes treated with the Boston type I keratoprosthesis.

Purpose: To describe the incidence, timing, visual significance, and management of posterior segment complications after Boston type I keratoprosthesis implantation. Methods: A retrospective chart review was conducted of all consecutive Boston type I keratoprostheses implanted by a single surgeon at a single institution over a 6-year period. Preoperative demographics, postoperative complications, and postoperative visual acuity outcomes were analyzed. Results: One hundred and ten keratoprostheses were implanted in 98 eyes of 94 patients during the period under review. A minimum of 6-month follow-up was available for 83 eyes, with a mean follow-up of 28.2 months (range 6–84 months, median 23.7 months). The mean time to occurrence of any posterior segment complication was 5.6 months (range 0–42.1 months, median 5.2 months, n = 38). After keratoprosthesis surgery, 63% of all eyes had corrected distance visual acuity of 20/200 or better at last follow-up compared with 10% of eyes preoperatively. Thirty-eight eyes (40.9%) experienced at least 1 postoperative posterior segment complication, the most common of which were retinal detachment (16.9%, 14 of 83), choroidal detachment (16.9%, 14 of 83), and sterile vitritis (14.5%, 12 of 83). Corrected distance visual acuity was worse among eyes that experienced posterior segment complications compared with eyes that did not at multiple postoperative follow-up intervals (statistically significant up to 3 years) and at last follow-up (logarithm of the minimum angle of resolution ± SD = 1.45 ± 0.78 vs. 0.89 ± 0.81, P = 0.003). Conclusion: Posterior segment complications occur in a significant percentage of patients after keratoprosthesis surgery, resulting in a persistent reduction of visual acuity in a significant proportion of the affected eyes (corrected distance visual acuity ⩽ 20/400 in 61% with complications vs. 24% without complications at last follow-up). Given this, and the anatomic difficulties associated with management of posterior segment complications after keratoprosthesis implantation, it is of particular importance to prevent posterior segment complications, whenever possible, in keratoprosthesis patients.

Efficacy of intravitreal ocriplasmin on vitreomacular traction and full-thickness macular holes.

PURPOSE To analyze a single centers experiences with ocriplasmin on vitreomacular traction (VMT) and the rate of VMT release, full-thickness macular hole (full-thickness MH) closure, and best-corrected visual acuity (BCVA) changes. DESIGN Retrospective interventional case series. METHODS Single-center study of 58 eyes of 56 patients who received intravitreal ocriplasmin for VMT with or without full-thickness MH. VMT release, full-thickness MH closure, visual acuity changes, and anatomic characteristics on spectral-domain optical coherence tomography (SD OCT) were analyzed. RESULTS VMT resolved in 29 of 58 eyes (50%) and nonsurgical closure of full-thickness MH was achieved in 4 of 15 eyes (27%). Mean logMAR BCVA among all treated eyes improved from 0.51 (20/65) at baseline to 0.36 (20/46) at final follow-up (P = .0018) with mean follow-up of 8.7 months. When compared to eyes without VMT release, eyes with successful vitreomacular release had a better pretreatment BCVA (20/48 vs 20/89, P = .004) and final follow-up BCVA (20/31 vs 20/68, P = .0001). Improvement in BCVA was significant in eyes with VMT release (P = .0001). Transient ellipsoid zone changes were noted in 26% of treated eyes (n = 15), of which 14 had successful VMT release. Transient subfoveal fluid accumulation was noted in all these patients with vitreomacular release. Mean time to resolution of ellipsoid zone changes was within 38 days. CONCLUSION In clinical practice, intravitreal injection of ocriplasmin achieved VMT release in approximately one half of treated eyes, with a 27% closure rate for full-thickness MH. Transient ellipsoid changes were evident in 26% of treated eyes, more common in eyes with successful VMT release.

Endophthalmitis in microincision vitrectomy: outcomes of gas-filled eyes.

Purpose: To assess whether performing an air or gas exchange at the conclusion of a microincision vitrectomy procedure is beneficial regarding the rate of endophthalmitis. Methods: This was a collaborative, multicenter, retrospective chart review of 2,336 eyes that underwent microincision sutureless vitrectomy (23 or 25 gauge) with either SF6 or C3F8 gas endotamponade for macular hole between January 2008 and December 2009. For all eyes, the search methodology was structured to identify the main outcome measure, which was the occurrence of acute postoperative endophthalmitis (<6 weeks after pars plana vitrectomy). Results: Of the cumulative 2,336 consecutive cases over a 2-year period, only 1 (0.04%) had postoperative endophthalmitis. All eyes had near-complete gas-fluid exchange at the end of surgery; C3F8 was the most common endotamponade agent. The majority of cases were performed with 23-gauge vitrectomy. No other complications were noted. Conclusion: Endophthalmitis was a rare occurrence in this large series of gas-filled eyes after macular hole surgery (0.04%). Gas endotamponade after microincision sutureless vitrectomy may be beneficial in reducing the risk of postoperative endophthalmitis; however, additional studies are necessary to make a definitive recommendation.

Postoperative vitreous hemorrhage after diabetic 23-gauge pars plana vitrectomy.

PURPOSE To report the frequency of postoperative vitreous hemorrhage (VH) in eyes that underwent primary 23-gauge pars plana vitrectomy (PPV) for nonclearing VH resulting from proliferative diabetic retinopathy, as well as associated risk factors. DESIGN Retrospective, consecutive, interventional case series. METHODS SETTING Institutional (Retina Service of Wills Eye Institute). STUDY POPULATION One hundred seventy-three eyes of 157 patients. INTERVENTION Twenty-three-gauge PPV for nonclearing diabetic VH. MAIN OUTCOME MEASURES Percentage of eyes in which postoperative VH developed, categorized as early, delayed, or severe persistent, as well as percentage requiring reoperation. RESULTS During a mean follow-up of 32 weeks, 56 (32%) of 173 eyes demonstrated postoperative VH, categorized as early (8 eyes; 5%), delayed (13 eyes; 8%), or severe persistent (35 eyes; 20%). Twenty-two (13%) of 173 eyes required reoperation: 4 (50%) of 8 in the early group, 8 (62%) of 13 in the delayed group, and 10 (29%) of 35 in the severe persistent group. Mean preoperative logarithm of the minimum angle of resolution visual acuity was 1.5 (Snellen equivalent, approximately 20/600); mean postoperative VA was 0.65 (Snellen equivalent, approximately 20/90), a gain of 0.85 (P < .0001). Thirty-four (27%) of 127 eyes with complete scatter photocoagulation before undergoing PPV compared with 22 (48%) of 46 eyes with incomplete scatter photocoagulation before undergoing PPV demonstrated postoperative VH (P = .002). Other factors associated with postoperative VH included younger age (P = .022) and phakia (P = .036). CONCLUSIONS Postoperative VH was not uncommon after initial 23-gauge PPV for diabetic VH and was associated with incomplete scatter photocoagulation, younger age, and phakia before PPV. However, only a minority of patients required reoperation.

Serous Macular Detachment in Waldenström Macroglobulinemia: A Report of Four Cases

PURPOSE To describe a series of 4 patients with Waldenström macroglobulinemia and serous macular detachment, and propose a mechanism for development of subretinal fluid based on optical coherence tomography (OCT) findings. DESIGN Retrospective observational case series. METHODS The records of patients with Waldenström macroglobulinemia and OCT documentation of serous macular detachment at Wills Eye Institute were reviewed. Data collection included clinical examination, as well as findings on fluorescein angiography (FA) and OCT. RESULTS Four patients (8 eyes) with Waldenström macroglobulinemia and serous retinal detachment were identified. All eyes had varying degrees of venous stasis retinopathy and intraretinal edema overlying the macular detachment. Three patients had no FA leakage, while 1 patient had macular leakage in a petaloid pattern. Focal outer retinal defects within the detached retina were seen in 4 eyes on OCT imaging. In one eye, development of cystoid macular edema was observed before the outer retinal defect and serous macular detachment. All patients with serous macular detachment had some degree of outer retinal disruption. CONCLUSION Discontinuity of the outer retina within the macular detachment may enable immunoglobulins along with accumulated intraretinal fluid to flow into the subretinal space, creating a serous retinal detachment. Even with systemic treatment of the underlying Waldenström macroglobulinemia, the visual prognosis was guarded.

Intravitreal bevacizumab for choroidal neovascularization associated with choroidal nevus.

Purpose: To report 10 cases of occult choroidal neovascularization (CNV) associated with choroidal nevus managed with intravitreal bevacizumab. Methods: Interventional case series. Each nevus was examined and imaged with fluorescein angiography, B-scan ultrasonography, and optical coherence tomography. Data were retrospectively analyzed to evaluate outcomes of treatment response and visual acuity. Results: Nine patients presented with CNV overlying a chronic choroidal nevus with a posterior margin within 1.5 mm of the foveola. In the 10th patient, the posterior margin of the nevus was located 10 mm from the foveola with extension of subretinal fluid into the macula. The CNV was subfoveolar in four cases, juxtafoveolar in two cases, and extrafoveolar in four cases. Initial visual acuity was 20/20 to 20/50 in 5, 20/60 to 20/100 in 2, and 20/200 or worse in 3 cases. Clinical features included subfoveolar fluid in nine, exudation in five, and hemorrhage in four cases. Intravitreal bevacizumab (1.25 mg/0.05 cc) was injected with regression of CNV in all 10 cases using 2 to 14 injections (median 3 injections). In 2 eyes, after therapeutic response to bevacizumab later consolidation with photodynamic therapy (juxtafoveolar CNV) (n = 1) or conventional laser (extrafoveolar CNV) (n = 1) was provided. In the remaining 8 eyes, after discontinuation of bevacizumab, there was no recurrence of CNV over mean 10.1 months. At overall mean follow-up of 22.5 months, final visual acuity decreased by 1 line in 4 cases and improved by mean of 3 lines (range, 1–8 lines) in 6 cases. There were no adverse effects from bevacizumab injections. All 10 choroidal nevi remained stable. Conclusion: Intravitreal bevacizumab appears to be an effective treatment option for CNV secondary to choroidal nevus. In some cases, depending on the proximity of the CNV to the foveola, photodynamic therapy or conventional laser may be useful adjunctive therapy.