Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: A vehicle-controlled, randomized clinical trial.

PURPOSE: Meibomian gland dysfunction (MGD) is a chronic progressive disease with downstream effects on ocular signs and symptoms. AZR-MD-001 is a selenium sulfide ophthalmic ointment that was investigated as a potential treatment option for patients with MGD. METHODS: A Phase 2, multi-center, double-masked, parallel group study was conducted across 29 sites, with 245 patients randomized 1:1:1 to AZR-MD-001 0.5%, AZR-MD-001 1.0% or vehicle applied to the lower eyelid, twice weekly. Patients were eligible for the trial if they presented with signs and symptoms of MGD. Co-primary efficacy endpoints were the changes from baseline in number of open glands (Meibomian Glands Yielding Liquid Secretion [MGYLS] score) and patient-reported ocular surface symptoms (Ocular Surface Disease Index [OSDI] total score) at Month 3. Efficacy outcomes were captured at Day 14, Month 1.5 and Month 3. Safety and tolerability were assessed for treatment-emergent adverse events (TEAEs). RESULTS: AZR-MD-001 0.5% (n = 82 patients) treatment resulted in significant improvements in MGYLS score, with patients experiencing an average increase from baseline of 4.2 and 2.4 open glands secreting meibum for the drug and vehicle, respectively (p < 0.001) and from baseline a mean OSDI total score improvement of 7.3 and 3.8 for the drug and vehicle, respectively (p < 0.05). Most TEAEs were mild and transient, with 3 serious adverse events (SAEs) reported with AZR-MD-001 (none related to study drug). CONCLUSIONS: Co-primary endpoints were met for AZR-MD-001 0.5% at Month 3, with a statistically significant improvement in the signs and symptoms of MGD. AZR-MD-001 was safe and well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03652051, ANZCTR Registration Number: AZ201801.

Six-Month Intraocular Pressure Reduction with a Topical Bimatoprost Ocular Insert: Results of a Phase II Randomized Controlled Study.

PURPOSE: Improving adherence to manage elevated intraocular pressure (IOP) remains an unmet need. A topical bimatoprost ocular insert was compared with twice-daily timolol eye drops in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) treated for 6 months. DESIGN: Parallel-arm, multicenter, double-masked, randomized, controlled trial. PARTICIPANTS: One hundred thirty adult OAG or OHT patients. METHODS: Eligible patients were randomized 1:1 to receive a bimatoprost insert plus artificial tears twice daily or a placebo insert plus timolol (0.5% solution) twice daily for 6 months after a screening washout period. Diurnal IOP measurements (at 0, 2, and 8 hours) were obtained at baseline; weeks 2, 6, and 12; and months 4, 5, and 6. Key eligibility included washout IOP of 23 mmHg or more at time 0, IOP of 20 mmHg or more at 2 and 8 hours, and IOP of 34 mmHg or less at all time points; no prior incisional surgery for OAG or OHT; and no known nonresponders to prostaglandins. MAIN OUTCOME MEASURES: The primary efficacy end point examined the difference in mean change from baseline in diurnal IOPs (point estimate, 95% confidence interval) across 9 coprimary end points at weeks 2, 6, and 12 comparing the bimatoprost arm with the timolol arm using a noninferiority margin of 1.5 mmHg. Secondary end points were diurnal IOP measurements at months 4, 5, and 6 and adverse events (AEs). RESULTS: A mean reduction from baseline IOP of -3.2 to -6.4 mmHg was observed for the bimatoprost group compared with -4.2 to -6.4 mmHg for the timolol group over 6 months. The study met the noninferiority definition at 2 of 9 time points but was underpowered for the observed treatment effect. Adverse events were consistent with bimatoprost or timolol exposure; no unexpected ocular AEs were observed. Primary retention rate of the insert was 88.5% of patients at 6 months. CONCLUSIONS: Clinically relevant reduction in mean IOP was observed over 6 months with a bimatoprost ocular insert and seems to be safe and well tolerated. The topically applied bimatoprost insert may provide an alternative to daily eye drops to improve adherence, consistency of delivery, and reduction of elevated IOP.

Preferential Hyperacuity Perimetry to detect hydroxychloroquine retinal toxicity.

PURPOSE: To determine if Preferential Hyperacuity Perimetry (PHP) testing can detect the presence of retinal toxicity due to hydroxychloroquine (HCQ) or chloroquine administration. METHODS: Fifteen patients were divided into three groups. Five patients had confirmed HCQ or chloroquine toxicity, five patients had suspected HCQ toxicity, and five patients had history of long-term use of HCQ or chloroquine but no evidence of toxicity. All patients underwent PHP testing. RESULTS: All patients with either known or suspected toxicity based upon standardized visual field testing and/or fluorescein angiography demonstrated significant hyperacuity defects on PHP testing. None of the patients on long-term HCQ therapy, without clinical suspicion of toxicity, demonstrated a PHP hyperacuity defect. CONCLUSION: Results of this pilot study with patients with known or suspected HCQ or chloroquine toxicity suggest that PHP may be a useful adjunct for testing of patients suspicious for toxicity due to these medications. Further testing is warranted.

Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

PURPOSE: To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. DESIGN: Prospective, comparative, concurrent, nonrandomized, multicenter study. PARTICIPANTS: Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. METHODS: After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. MAIN OUTCOME MEASURES: A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. RESULTS: Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). CONCLUSIONS: Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the intermediate stage of AMD.

Results of a multicenter clinical trial to evaluate the preferential hyperacuity perimeter for detection of age-related macular degeneration.

PURPOSE: To compare the preferential hyperacuity perimeter (PHP) with an Amsler grid in detection of age-related macular degeneration (AMD). METHODS: Patients underwent refraction, visual acuity examination, PHP, Amsler grid examination, and macular photography. RESULTS: One hundred fifty patients participated in the trial. Of 19 eyes with neovascular AMD, 19 (100%) were positive on the PHP, and 10 (53%), on the Amsler grid. Of 27 eyes with geographic atrophy, 26 (96%) were positive on the PHP, and 12 (44%), on the Amsler grid. Of 20 eyes with intermediate AMD, 14 (70%) were positive on the PHP, and 4 (20%), on the Amsler grid. Of 51 eyes with early AMD, 21 (41%) were positive on the PHP, and 4 (8%), on the Amsler grid. Of 33 eyes with no AMD, 6 (18%) were positive on the PHP, and none, on the Amsler grid. Thus, 80 (68%) of 117 patients with AMD had a positive PHP, while 30 (26%) had positive results of Amsler grid examination (P < 0.001, McNemar test). CONCLUSION: The PHP had greater sensitivity, although with a relatively high rate of false-positive results for healthy individuals, than the Amsler grid in detecting AMD-related lesions.

A novel high-resolution kinetic method for visual field mapping of scotoma in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To examine a new high-resolution kinetic mapping method for scotoma in age-related macular degeneration. PATIENTS AND METHODS: A computer-based program for kinetic visual field mapping was tested in 10 healthy subjects and 14 patients with age-related macular degeneration and fixed preferred retinal locus. The stimulus was presented using a back projector on a screen located 40 cm from the subject. The findings were then compared with static results. RESULTS: Control group mapping revealed good congruency with the anatomic blind spot. Mapping of the 14 patients with age-related macular degeneration was rapid and revealed good accuracy. The average deviation of the mapping border from the anatomic scotoma border was no more than 3.1% of the scotoma radius. Static mapping of 7 of the patients with age-related macular degeneration was longer and revealed lower accuracy. CONCLUSIONS: The proposed method is more rapid, accurate, and consistent than static mapping. It allows accurate mapping of central scotoma with suprathreshold stimulus, and may be used in the future for detecting the early stages of age-related macular degeneration using subthreshold stimulus.

Red blood cell membrane mechanical fluctuations in non-proliferative and proliferate diabetic retinopathy.

PURPOSE: To study whether cell membrane mechanical fluctuation (CMF) of red blood cells (RBCs) are attenuated in non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: Point dark-field microscopy-based recordings of local membrane displacements (frequency 0.3-25 Hz) were compared between type 2 diabetes patients with mild-to-moderate and severe NPDR and type 2 diabetes patients with PDR. The matched control group, corresponding to each stage of diabetic retinopathy, was based on non-diabetic patients who were evaluated in our clinic due to cataract. RESULTS: The average mean values of the maximal CMF amplitude did not differ between RBCs of NPDR patients (n=20) and controls (n=20) (19.5+/-1.5% and 19.6+/-1.7%, respectively). A statistically significant decrease in CMF amplitudes was observed in patients with PDR compared with patients with a non-proliferative disease (NPDR -20%, PDR -90%). CONCLUSION: This new rheological characteristic demonstrates differences in the mechanical properties of RBCs in different stages of diabetic retinopathy. The significant reduction in CMF in patients with PDR may shed more light on the possible mechanism modulating retinal ischemia and leading to angiogenesis in these patients. Larger-scale studies are needed to evaluate these findings and the possible correlation between significantly lower CMF values and the progression of diabetic retinopathy.

Interferon alpha-2a for proliferative diabetic retinopathy after complete laser panretinal photocoagulation treatment.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the effect of interferon alpha-2a, an angiogenesis inhibitor, on eyes with active neovascularization after complete laser panretinal photocoagulation treatment. PATIENTS AND METHODS: Eight patients with active neovascularization persisting for 6 months or more after completion of full panretinal photocoagulation were included in the study. All patients were treated with subcutaneous injections of 6 million international units of interferon alpha-2a, 3 times a week, for an average period of 10 months. Visual acuity, contrast sensitivity, blood tests, fundus photographs, fluorescein angiography, and physical examination were performed periodically. The main outcome measures were visual acuity and extent of neovascularization as assessed by fundus photography and fluorescein angiography. RESULTS: The 5 men and 3 women (mean age, 60 years) had a mean duration of diabetes of 19 years. The average study follow-up was 42.2 +/- 8.7 weeks. Visual acuity and extent of neovascularization improved or remained stable in 7 patients. In none of the patients was there progression of neovascularization, but in 1 patient it could not be assessed due to vitreous hemorrhage. Most patients had malaise during the first weeks of treatment, but none of the patients suffered from nonreversible side effects associated with interferon alpha-2a. CONCLUSION: This pilot study provides evidence that interferon alpha-2a might have a role in the regression of proliferative diabetic retinopathy and that further investigation is warranted.

Replacing the Amsler grid: a new method for monitoring patients with age-related macular degeneration.

PURPOSE: To investigate a method that uses hyperacuity, the Macular Computerized Psychophysical Test (MCPT), to evaluate the central macular visual field in patients with age-related macular degeneration (AMD). DESIGN: Prospective case-control study of a diagnostic test. PARTICIPANTS AND CONTROLS: One hundred eight eyes of 108 Patients with AMD and 51 eyes of 51 age-matched patients with no retinal disease. Patients with AMD included 32 (30%) patients with choroidal neovascularization (CNV), 23 (21%) with geographic atrophy (GA), 35 (32%) with AMD with high-risk characteristics (HRC), and 18 (17%) with early AMD with non-HRC. TESTING: Each subject underwent the MCPT, in which a virtual line composed of dots (white dots on a black background, maximal contrast) is flashed across different macular loci to a perifoveal radius of 7 degrees. Patients' responses were recorded and automatically analyzed using a specific algorithm developed before the onset of the study. All patients also underwent a supervised Amsler grid examination on the encounter before or after the MCPT in random order. MAIN OUTCOME MEASURES: Distortion, scotoma, or blurring perceived by the patient after a swift change of fixation was considered positive on the MCPT. Any perception of distortion, scotoma, or blurring was considered positive on the Amsler grid. RESULTS: Of the 32 patients with CNV, 30 (94%) were found positive on the MCPT and 11 (34%) were found positive on the Amsler grid. Of the 23 GA patients, 21 (91%) were found positive on the MCPT and 7 (30%) were found positive on the Amsler grid. Of the 35 HRC patients, 28 (80%) were found positive on the MCPT and 3 (9%) were found positive on the Amsler grid, and of the 18 early AMD with non-HRC patients, 8 (44%) were found positive on the MCPT and 3 (17%) were found positive on the Amsler grid. Of the 51 controls, 3 (6%) were positive on the MCPT and 1 (2%) was positive on the Amsler grid. CONCLUSIONS: The MCPT was superior to the Amsler grid in detecting AMD-related lesions in this cohort. Studies are underway to determine whether the MCPT is feasible for home monitoring to provide early detection of progression to CNV.

Colchicine in tear fluid of treated patients with familial Mediterranean fever.

PURPOSE: The study aimed to determine whether detectable concentrations of colchicine are present in the tear fluid of treated patients with familial Mediterranean fever (FMF) and thus demonstrate a possible route by which colchicine reaches the corneal surface. METHODS: Tear fluid samples (50-100 microL) were collected from eight FMF patients on long-term colchicine treatment. Colchicine tear fluid concentrations were determined in all patients by radioimmunoassay using goat anticolchicine antibodies and [3H]colchicine (Dupont, Wilmington, DE). RESULTS: Detectable concentrations of colchicine, with no apparent effect on the ocular surface, were found in all tear fluid samples (median, 0.46 ng/mL; range, 0.24-1.05 ng/mL). CONCLUSIONS: This study provides evidence of the route by which colchicine, given systemically, reaches the corneal surface and thus gives credence to the possible inhibitory effect of this drug on corneal wound healing in the cases described in the literature.

Macular hole secondary to branch retinal vein occlusion diagnosed by Retinal Thickness Analyzer.

The Retinal Thickness Analyzer is a laser slit biomicroscopy imaging device that produces accurate measurements of retinal thickness and displays the images in a two-dimensional pattern, superimposed on a fundus image. This article reports a patient with decreased vision following branch retinal vein occlusion in whom the Retinal Thickness Analyzer was used to establish the diagnosis of a macular lamellar hole that was not apparent clinically.