Nelson R. Sabates

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.

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.

Laser treatment in fellow eyes with large drusen: Updated findings from a pilot randomized clinical trial

PURPOSE To update the findings from the Choroidal Neovascularization Prevention Trial (CNVPT) with respect to resolution of drusen, incidence of choroidal neovascularization, and visual function. DESIGN A multicenter, randomized, controlled, pilot clinical trial. PARTICIPANTS The 120 patients enrolled in the CNVPT. Patients had signs of choroidal neovascularization or retinal pigment epithelial detachment in 1 eye and had >/=10 large (>63- micro m) drusen in the contralateral, or fellow, eye. INTERVENTION The fellow eye of 59 patients was assigned randomly to argon green laser treatment consisting of multiple 100- micro m spots at least 750 micro m from the center of the fovea. The fellow eye of the remaining 61 patients was assigned randomly to observation. MAIN OUTCOME MEASURES Change in visual acuity was the primary outcome measure. Incidence of choroidal neovascularization, resolution of drusen, change in contrast threshold, change in critical print size for reading, and incidence of geographic atrophy were secondary outcome measures. RESULTS Throughout 4 years of follow-up, there were no statistically significant differences in change in visual acuity, contrast threshold, critical print size, or incidence of geographic atrophy. With additional follow-up, the large increase in the incidence of choroidal neovascularization observed within 18 months of treatment was maintained; however, by 30 months, the incidence in the two treatment groups was the same. Most drusen resolution in treated eyes occurred within 24 months of the initial treatment. Treated eyes that received higher-intensity laser burns had an increased risk of choroidal neovascularization. Among eyes developing choroidal neovascularization in each treatment group, most lesions (two thirds or more) were composed of occult neovascularization only. CONCLUSIONS Laser treatment as applied in the CNVPT caused an excess risk of choroidal neovascularization in the first year or so after treatment. The increased early incidence of choroidal neovascularization was not associated with either a harmful or beneficial effect in this pilot study.

Scanning laser ophthalmoscope macular perimetry in the evaluation of submacular surgery.

PURPOSE Submacular surgery for choroidal neovascularization (CNV) is under investigation in the treatment of age-related macular degeneration (AMD) and the presumed ocular histoplasmosis syndrome. Four case studies are presented to demonstrate scanning laser ophthalmoscope (SLO) testing in the pre- and postsurgical evaluation of visual function in patients with subfoveal CNV secondary to AMD, presumed ocular histoplasmosis syndrome, and submacular hemorrhage secondary to AMD. METHODS Patients underwent a visual assessment pre- and 6 months postoperatively, consisting of low vision visual acuity measurement, SLO macular perimetry of dense and relative scotomas, and analysis of the preferred retinal locus for fixation (PRL) location and ability. RESULTS Visual acuity, dense and relative scotoma size and location, and PRL location were compared; and relationships between anatomic and functional changes were observed. Decreases in scotoma size and improvement in PRL location and ability usually corresponded with improved visual acuity. Preoperative scotoma and PRL location guided retinotomy site selection. CONCLUSION Scanning laser ophthalmoscope macular perimetry and PRL testing may be useful adjuncts in the visual assessment of submacular surgery and may advance under-standing of the effects of submacular surgery on visual function. In addition, this testing may be used to plan location of surgical interventions for macular diseases.

Survey of CT and MR imaging of the orbit

Diseases of the orbit encompass a diverse group of lesions. They are classified according to their site of origin within and outside of the orbital cavity, along with the nature of the pathological process, such as inflammatory disease, cysts, and benign and malignant tumors [11 (Tables 1, 2). Computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice in the assessment of these lesions [2]. CT, with different window settings, delineates, to great advantage, the various soft tissue structures, but especially the bony structures and areas of calcification. MR is insufficient in the detailed analysis of bone and calcification, but is superior to CT in visualization of the globe, optic nerve abnormalities, and intracranial extension of lesions. In addition, MR provides better lesion characterization (especially tumors), based on the signal intensity differences of various tissues and increased conspicuity of lesions following introduction of gadolinium and fat suppression [3,4].

Clinical application of optical coherence tomography in combination with functional diagnostics: advantages and limitations for diagnosis and assessment of therapy outcome in central serous chorioretinopathy

Purpose While identifying functional and structural parameters of the retina in central serous chorioretinopathy (CSCR) patients, this study investigated how an optical coherence tomography (OCT)-based diagnosis can be significantly supplemented with functional diagnostic tools and to what degree the determination of disease severity and therapy outcome can benefit from diagnostics complementary to OCT. Methods CSCR patients were evaluated prospectively with microperimetry (MP) and spectral domain optical coherence tomography (SD-OCT) to determine retinal sensitivity function and retinal thickness as outcome measures along with measures of visual acuity (VA). Patients received clinical care that involved focal laser photocoagulation or pharmacotherapy targeting inflammation and neovascularization. Results Correlation of clinical parameters with a focus on functional parameters, VA, and mean retinal sensitivity, as well as on the structural parameter mean retinal thickness, showed that functional measures were similar in diagnostic power. A moderate correlation was found between OCT data and the standard functional assessment of VA; however, a strong correlation between OCT and MP data showed that diagnostic measures cannot always be used interchangeably, but that complementary use is of higher clinical value. Conclusion The study indicates that integrating SD-OCT with MP provides a more complete diagnosis with high clinical relevance for complex, difficult to quantify diseases such as CSCR.

Spectral Domain Optical Coherence Tomography Findings of Retinal Macroaneurysm.

A 47-year-old healthy male presented to the ophthalmology clinic with complaint of dry eyes. Examination revealed visual acuity 20/20 in both eyes (OU). Anterior segment examination was normal. Fundus examination and fluorescein angiogram findings were consistent with a non-ruptured macroaneurysm. Spectral domain (SD) optical coherence tomography (OCT) (Ophthalmic Technologies, Ontario, Canada) demonstrated a large 215 mu lumen with inferior hyperreflectivity at the area of hemorrhage. There was focal thickening of the retina to encompass the macroaneurysm but no associated retinal edema. The higher resolution afforded by SD OCT may allow more accurate measurement of the size of the aneurysm, making it possible to evaluate prognostically relevant characteristics of the aneurysm such as hemorrhage in the vessel wall or thrombus in the lumen. This may also allow us to possibly intervene earlier in high-risk cases. SD OCT may be of value in management of retinal macroaneurysm.

Penicillin-resistant Streptococcus pneumoniae Endophthalmitis

PURPOSE To report a case of trabeculectomy-associated endophthalmitis caused by penicillin-resistant Streptococcus pneumoniae. METHOD Case report. RESULTS The patient developed endophthalmitis 1 month after an uncomplicated trabeculectomy for primary open-angle glaucoma. Vitreous cultures grew abundant, highly penicillin-resistant S pneumoniae. Despite aggressive treatment with vitrectomy and intravitreal injections of vancomycin hydrochloride and amikacin sulfate, the patient had a poor visual outcome. CONCLUSION Penicillin-resistant S pneumoniae can cause endophthalmitis after trabeculectomy.

Spectral domain optical coherence tomography findings of acute branch retinal artery occlusion from calcific embolus

An 82-year-old female presented with sudden painless decrease in vision in the right eye after awakening. She could see the “superior half” of her vision from the right eye only. On examination, best-corrected vision was 20/300 in the right eye and 20/30 in the left eye. The fundus in the right eye revealed recent superotemporal branch retinal artery occlusion (BRAO) with calcified plaque at the disc. Spectral domain optical coherence tomography (OCT) (OTI Ophthalmic Technologies, Inc.), revealed hyperreflectivity and increased thickness of the inner retinal layers of the superior compared to the inferior retina. Imaging at the optic disc revealed the blocked artery containing a highly reflective material. The high reflectivity of the material and underlying optical shadowing could be characterized as calcific emboli.

Microperimetric assessment of retinal sensitivity in eyes with diabetic macular edema from a phase 2 study of intravitreal aflibercept

Purpose: To evaluate retinal sensitivity in patients with diabetic macular edema who received intravitreal aflibercept injection (IAI) or laser. Methods: A substudy included 46 patients from DA VINCI (a randomized, double-masked Phase 2 study) receiving either laser, 0.5 mg IAI every 4 weeks, 2 mg IAI every 4 weeks, 2 mg IAI every 8 weeks after 3 monthly doses (2q8), or 2 mg IAI as-needed after 3 monthly doses for 52 weeks. Retinal sensitivity was measured in one (central), five (one central and four inner), and eight (four inner and four outer) optical coherence tomography subfields. Results: Mean best-corrected visual acuity improvement in the subgroup at Week 52 was 3.3 letters with laser and ranged from 5.4 to 16.3 letters in the IAI groups. Retinal sensitivity of laser patients at Week 52 was comparable with baseline in the central optical coherence tomography subfield but decreased in the five and eight optical coherence tomography subfields. Compared with laser, retinal sensitivity significantly increased with IAI in the 2q8 and pooled IAI groups in the 5 and 8 optical coherence tomography subfields at Week 52 (P < 0.05). Conclusion: Intravitreal aflibercept injection improved best-corrected visual acuity and retinal sensitivity in this subgroup of patients. Laser may cause a deterioration of macular function that is not detectable with best-corrected visual acuity testing.