Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma.

PRéCIS:: This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure (IOP) to a greater degree in angle-closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma. PURPOSE: Endocyclophotocoagulation (ECP) laser treatment of the ciliary processes is believed to decrease IOP by reducing aqueous production. Anecdotal experience in angle-closure glaucoma suggests that it may also lower IOP by opening the drainage angle to promote aqueous outflow. This study sought to evaluate combined phacoemulsification and ECP (phaco/ECP) in eyes with different types and stages of glaucoma. PATIENTS AND METHODS: A Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution was conducted. RESULTS: In 63 eyes of 63 patients with an average of 3.0±1.7 years of follow-up, the 22 eyes with chronic angle-closure glaucoma (CACG) had greater IOP reduction and medication reduction than the 41 eyes with primary open-angle glaucoma at both 1 year (6.4 vs. 2.1 mm Hg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4 mm Hg, P=0.02; 0.9 vs. 0.3 medications, P=0.05). There was no difference in IOP reduction or medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11; 0.1, 0.8, 0.4 medications, P=0.14). CONCLUSIONS: Eyes with CACG were more responsive to phaco/ECP in terms of IOP and medication reduction compared with eyes with primary open-angle glaucoma. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Phaco/ECP was effective in all stages of glaucoma.

The ISNT Rule: How Often Does It Apply to Disc Photographs and Retinal Nerve Fiber Layer Measurements in the Normal Population?

PURPOSE: To determine what percentage of normal eyes follow the ISNT rule, and whether ISNT rule variants may be more generalizable to the normal population. DESIGN: Cross-sectional study. METHODS: Setting: Institutional setting. STUDY POPULATION: Total of 110 normal subjects. OBSERVATION PROCEDURES: Neuroretinal rim assessments from disc photographs and retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography. MAIN OUTCOME MEASURES: The percentages of subjects that obeyed the ISNT rule and its variants. RESULTS: The ISNT rule is only valid for 37.0% of disc photograph rim assessments and 43.8% of RNFL measurements. Deviation of the nasal sector from the expected ISNT pattern was a major cause for the ISNT rule not being obeyed for both rim and RNFL assessments. Specifically, 10.9% of subjects had wider nasal rims than the inferior rims, 29.4% had wider nasal rims than the superior rims, 14.7% had narrower nasal rims than the temporal rims, and 42.9% had thinner nasal RNFLs compared to the temporal quadrant. Exclusion of the nasal quadrant from the ISNT rule significantly increased the validity of ISNT variant rules, with 70.9% and 76.4% of disc photographs following the IST rule and the IS rule, respectively. Similarly, for RNFL thickness, 70.9% and 71.8% of patients followed the IST and IS rule, respectively. CONCLUSIONS: The ISNT rule is only valid for about a third of disc photographs and less than half of RNFL measurements in normal patients. ISNT rule variants, such as the IST and IS rule, may be considered, as they are valid in more than 70% of patients.

Intraocular properties of a repository urokinase receptor antagonist a36 Peptide in rabbits.

PURPOSE: To evaluate the intraocular properties of A36, a peptide that directly antagonizes the cell surface urokinase receptor and so prevents pericellular urokinase plasminogen activator activity. METHODS: A total of 41 rabbits were used. The toxicity study tested three doses of A36: 1 mg/ eye, 0.3 mg/eye, and 0.1 mg/eye. At 2 and 12 weeks, eyes were evaluated by ERG and histology. Pharmacokinetics were studied in rabbit eyes with the dose of 1 mg/eye in two different formulations: a micronized preparation and a non-micronized formulation. Eyes were enucleated at months 1, 2, 3, 4, and 5. Vitreous, retina, and choroid were collected separately for active A36 analysis. RESULTS: We did not find ocular toxicity with low and medium doses. At the highest dose, there was a transient toxicity at 2 weeks but was not notable at 3 months. The target choroid concentration of A36 was chosen as > or =100 nM. The micronized formulation at months 1, 2, and 3 combined, showed variable levels in the choroid giving 5/10 (50%) of the therapeutic level; the non-micronized formulation at months 4 and 5 combined, gave 6/7 (86%) of the therapeutic level, although this difference was not statistically significant. CONCLUSION: A36 appears to be long lasting; the non-micronized formulation of A36 gave concentrations above therapeutic level in the choroid at months 4 and 5. Optimization of the formulation of A36, particularly the particle size, may result in a promising new compound for exudative age-related macular degeneration treatment.

Toxicity and intraocular properties of a novel long-acting anti-proliferative and anti-angiogenic compound IMS2186.

PURPOSE: To investigate the intraocular properties and toxicity of IMS2186, a small molecule developed as an anti-choroidal neovascularization (anti-CNV) drug. MATERIALS AND METHODS: Cellular toxicity and mechanism of action was tested on cell lines in vitro. Intraocular studies used rabbits for drug dissolution as well as toxicity and rats for the treatment study as well as the toxicity confirmation study. Rabbits' eyes were injected with 2.5 mg of IMS2186 and observed for 36 weeks. Laser-induced CNV in rats was treated with IMS2186, Kenalog, or phosphate-buffered saline (pBS). Fluorescein angiography (FA) and immunohistochemical processing of the globes was performed. RESULTS: The anti-proliferative IC(50) of IMS2186 for human fibroblast cells was 1.0-3.0 microM and 0.3-3.0 microM for human cancer cells; the IC(50) of IMS2186 to inhibit endothelial tube formation was 0.1-0.3 microM. The IC(50) of IMS2186 for inhibiting the production of pro-inflammatory cytokines was 0.3-1 microM. The IC(50) of IMS2186 for inhibiting macrophage migration was 1 micrM. These biological properties were not species specific. IMS2186 can be formulated as a suspension for long-lasting release and when delivered intraocularly, no intraocular toxicity was observed by slit lamp exam, fundus exam, intraocular pressure measurements, or by electroretinography. FA showed a reduction in the leakage in eyes treated with IMS2186 and triamcinolone acetonide; DAPI staining also showed significantly less cellularity in IMS2186-treated lesions as compared to PBS (p = 0.0025). CONCLUSION: IMS2186 may be a safe intraocular therapeutic agent for intraocular proliferation and angiogenesis.

Multifocal electroretinography in HIV-positive patients without infectious retinitis.

PURPOSE: To evaluate early changes in the central retinal response in human immunodeficiency virus (HIV)-positive patients without infectious retinitis using multifocal electroretinography (mfERG). DESIGN: Case control study. METHODS: We evaluated three cohorts: HIV-negative controls and two groups of HIV-positive patients separated according to their nadir CD4 counts (>or= 100 cells/mm(3) and < 100 cells/mm(3) for a minimum of six months). mfERG first-order kernels (FOKs) and second-order kernels (SOKs) were analyzed separately by areas of rings, quadrants, and individual hexagons for each cohort. RESULTS: Of 103 hexagon locations of FOK results, there were no significant differences in amplitudes of P1 and N1 across the groups (.05 < P < .50), although there was a trend for an overall reduction in the amplitudes. Similarly, latency N1 did not differ (.28 < P < .95). There were significantly delayed latencies of P1 between cohorts across 103 hexagons in both kernels. SOK results also showed significant delay in latencies of P1 and a trend of reduced P1 amplitudes across studied locations among cohorts (.24 < P < .08). CONCLUSIONS: The results demonstrate widespread delay in latency in HIV-positive patients, especially in those with prolonged low (below 100 cells/mm(3)) CD4 nadir counts. These findings suggest early diffuse dysfunction of the inner retina results from severe HIV disease even in the HAART era.

Comparison of visual acuity in macular degeneration patients measured with snellen and early treatment diabetic retinopathy study charts.

PURPOSE: To compare the measurements of visual acuity (VA) results measured with Snellen and Early Treatment Diabetic Retinopathy Study (ETDRS) charts in eyes with and without age-related macular degeneration (AMD). DESIGN: Cross-sectional study. PARTICIPANTS: One hundred four participants (190 eyes) selected from a university retina practice; 80 participants (142 eyes) had some degree of AMD. METHODS: Visual acuity was measured in each patient using standard procedure with both Snellen and ETDRS charts in random order. Statistical analysis of the results was performed. MAIN OUTCOME MEASURES: Difference in VA measured by both charts in logarithm of minimal angle of resolution (logMAR) notations. RESULTS: Overall, the mean Snellen VA was 0.78 logMAR (= 20/120), and the mean ETDRS VA in the same eye was 0.54 logMAR (= 20/70; P<0.001). In the low vision group (<20/200), represented by patients with AMD, the average difference in number of lines was considerably larger than in the good vision range (>20/30). On average, 20/200 on Snellen was 20/95 on ETDRS (>3 lines difference), and 20/30 on Snellen was 20/25 on ETDRS (<1 line difference). CONCLUSION: Our results show poor agreement between the Snellen and ETDRS charts, and it was more pronounced in the group with poor vision. The ETDRS measurements yielded better VA, particularly in participants with vision <20/200 (representing more advanced AMD patients). We suggest taking these findings into consideration when comparing outcomes in clinical practices (which typically measure VA using standard Snellen charts) with outcomes from clinical trials (which typically measure VA using ETDRS charts).

Changes of intraocular pressure after intravitreal injection of bevacizumab (avastin).

PURPOSE: To determine changes and need to monitor intraocular pressure (IOP) following intravitreal injection of bevacizumab (Avastin). METHODS: Seventy patients (122 injections) underwent an intravitreal injection of Avastin for exudative age-related macular degeneration treatment. Forty-one eyes (59%) had single injection, 29 eyes (41%) had repeated injections. IOP was measured before and after Avastin injection at 3, 10, and 15 minutes. Twenty-nine eyes were evaluated for baseline IOP changes after multiple injections. Statistical analysis was performed. RESULTS: Baseline mean IOP was 15.17 +/- 3.42 mm Hg, with range from 08 mm Hg to 23 mm Hg. Postinjection 3 minutes the IOP had risen to a mean of 36.27 +/- 5.1 mm Hg and fell spontaneously to a mean of 24.56 +/- 5.9 mm Hg at 10 minutes. Ten eyes (14%) needed 15 minutes to drop below 30 mm Hg. All eyes were below 30 mm Hg at 15 minutes. No significant change between multiple baseline IOP measurements was detected. CONCLUSION: Avastin injections caused a predictable probably volume-related rise in IOP which never occluded the central retinal artery and which spontaneously fell to below 30 mm Hg in all eyes within 15 minutes. This strong safety profile provides guidelines on monitoring IOP after Avastin injections. There was no IOP change after multiple injections.

Standardized visual acuity results associated with primary versus secondary bevacizumab (avastin) treatment for choroidal neovascularization in age-related macular degeneration.

PURPOSE: To compare standardized visual outcomes and macular thickness changes associated with primary and secondary bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) therapy for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). METHODS: Eighteen eyes received primary bevacizumab treatment; 20 eyes received pegaptanib (Macugen; Eyetech/OSI Pharmaceuticals, New York, NY) as initial treatment followed by bevacizumab therapy. Both medications were injected at 6-week intervals. Best-corrected visual acuity was measured with the ETDRS chart. Three- and 6-month data were analyzed for all eyes. RESULTS: Mean visual acuity improvement in the primary bevacizumab treatment cohort was 1.5 ETDRS lines at 3 months (P = 0.0009) and 2.2 ETDRS lines at 6 months (P=0.0004) compared with -0.4 ETDRS line at 3 months (P=0.27) and 0.2 ETDRS line at 6 months (P=0.70) in the secondary bevacizumab treatment group. Mean decrease in retinal thickness was also higher in the primary bevacizumab treatment group (90.9 microm [P=0.0037] vs 43.8 microm [P=0.13], respectively) than in the secondary bevacizumab treatment group (73.72 microm [P=0.051] vs 33.0 microm [P=0.21], respectively) at 3 months and 6 months. CONCLUSION: Primary bevacizumab therapy resulted in significantly greater visual improvement than secondary bevacizumab treatment at 3 months or 6 months. To our knowledge, this is the first report comparing primary bevacizumab treatment of CNV in AMD with secondary bevacizumab treatment after multiple pegaptanib injections.